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S.V. Harden
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MA 09 - The Current Status of Radiation Oncology (ID 666)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Locally Advanced NSCLC
- Presentations: 1
- Moderators:Tomoki Kimura, Yong Chan Ahn
- Coordinates: 10/17/2017, 11:00 - 12:30, Room 316
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MA 09.11 - Isotoxic Intensity Modulated Radiotherapy (IMRT) in Stage III Non-Small Cell Lung Cancer (NSCLC) – a Feasibility Study (ID 7978)
12:10 - 12:15 | Author(s): S.V. Harden
- Abstract
- Presentation
Background:
The majority of stage III patients with non-small cell lung cancer (NSCLC) are unsuitable for concurrent chemoradiotherapy. Alternative treatment options include sequential chemoradiotherapy and radiotherapy (RT) alone. As the rate of local failure is high there is a rationale for treatment intensification.
Method:
Isotoxic Intensity Modulated Radiotherapy (IMRT) is a multicentre feasibility study combining a number of intensification strategies; dose escalation, acceleration and hyperfractionation. Patients with inoperable stage III NSCLC, ECOG performance status (PS) 0-2, unsuitable for concurrent chemoradiotherapy were recruited. A minimum of 2 cycles of induction chemotherapy was mandated before RT. The dose of radiation was increased until one or more of the organs at risk (OAR) met predefined constraints or the maximum dose of 79.2Gy was reached. RT was delivered twice-daily in 1.8 Gy fractions. A RT quality assurance programme was in place. The primary end point was feasibility (>80% of patients achieving >60Gy EQD2 i.e. total biologically equivalent in 2 Gy fraction), with acute/late toxicity (CTCAE version 4.0), local control and overall survival as secondary end points.
Result:
Between June 2014 and March 2016, 37 patients were enrolled from 7 UK centres. Median age = 67 years (range 46-86). Male:female ratio = 18:19. ECOG PS=0, 5 (13.51%), PS=1, 29 (78.38%), PS=2, 3 (8.11%). Stage IIIa:IIIb ratio 23 (62.2%):14 (37.8%). Out of 37 patients, 2(5.4%) failed to achieve EQD2 >60Gy due to large tumour size and inability to meet OAR constraints, they received standard RT. This was due to large tumour size and inability to meet OAR constraints. Median prescribed tumour dose was 77.4Gy (61.2 – 79.2Gy) with the maximum dose of 79.2Gy delivered to 14 (37.8%) patients. All patients completed RT as scheduled except one due to disease progression. Grade (G)3 acute toxicities included: dysphagia 1 (2.9%), dypsnoea 2 (5.7%), lung infection 3 (5.7%) and radiation oesophagitis 2 (5.7%). There were three G5 events: radiation pneumonitis, trachea-oesophageal fistula and bronchopulmonary haemorrhage, which were probably treatment related. G3 late toxicities included: fatigue 1 (2.9%), dyspnoea 3 (8.6%) and 1 (2.9%) case of late G4 lung infection. At time of analysis median follow-up was 12.8 months for 20 survivors. Overall survival and progression-free survival at 1 year was 75% and 59% respectively.
Conclusion:
In the majority, treatment intensification using isotoxic IMRT is feasible. This regime will be tested alongside other intensified treatments against standard sequential chemoradiotherapy in the ADSCAN study (ISRCTN47674500).
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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 | Author(s): S.V. Harden
- 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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P1.05 - Early Stage NSCLC (ID 691)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Early Stage NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.05-010 - Curative Treatment Rates for Patients Diagnosed with Early Stage Non-Small Cell Lung Cancer (NSCLC) in England (ID 9889)
09:30 - 09:30 | Author(s): S.V. Harden
- Abstract
Background:
Overall survival for lung cancer in England has previously been shown to be improving year on year and to correlate with surgical resection rates (National Lung Cancer Audit (NLCA) 2016 report). Recently the NLCA switched to use anonymised data collected and processed by the National Cancer Registration and Analysis Service (NCRAS) which has allowed linkage of the dataset to other national datasets including the radiotherapy dataset (RTDS), not previously reported. The main aim of this study was to identify a national curative treatment rate for early stage NSCLC and to identify which patient features influence whether a patient receives surgery, radical radiotherapy (RT) or no active treatment.
Method:
A cross-sectional analysis was conducted on all English patients diagnosed with stage I-II lung cancer between January 2015 and December 2015. Types of surgery and radical radiotherapy were identified from NCRAS databases including Cancer Outcomes and Services Dataset (COSD), Hospital Episode Statistics (HES) and RTDS databases. Survival was defined from time from treatment until death and Cox regression analysis was used to determine factors associated with survival.
Result:
36025 cases of lung cancer were identified in 2015 with 8841 (28%) cases of stage IA-IIB proven or presumed NSCLC. 4560 (51.6%) cases received surgery and 1437 (16.2%) received radical RT creating a combined total of 5997 (67.8%) cases receiving treatment with curative intent. Curative intent treatment varied across cancer networks from 61.6% to 74.4%. Stereotactic Ablative Radiotherapy (SABR) was delivered in 750/1437 (52.2%) radical RT cases, generally for stage I disease, 60/1437 (4.1%) cases received Continuous Hyper-fractionated Accelerated RT (CHART) and 486/1437 (33.8%) cases received 55Gy/20 fractions, a commonly prescribed hypo-fractionated radical RT regime in England. Notably, 2844 (32.2%) patients did not receive treatment with curative intent, receiving either palliative therapy or supportive care only. Lack of treatment with curative intent was associated with increasing age and worsening performance status and varied across networks (25.6% - 38.4%). Updated survival data will be presented.
Conclusion:
In England for 2015, the curative treatment rate for stage I and II NSCLC was 67.8%. This means that almost one third of patients did not receive definitive treatment for their early stage lung cancer, ranging from 25.6% to 38.4 % across networks. A NLCA deep dive spotlight audit to identify more details about why these patients did not receive definitive treatment is planned for later this year.
