- W. Eberhardt (Essen, Germany)
- M. Guckenberger (Zürich, Switzerland)
- J. Zugazagoitia (New Haven, United States of America)
2O - Differentially regulated high-throughput CT imaging features correlate to distinct tumor immune contextures portraying a radiomic signature with prognostic impact on surgically resected NSCLC
- G. Mazzaschi (Parma, Italy)
- G. Mazzaschi (Parma, Italy)
- F. Quaini (Parma, Italy)
- G. Milanese (Parma, Italy)
- D. Madeddu (Parma, Italy)
- G. Bocchialini (Parma, Parma/PR, Italy)
- L. Ampollini (Parma, Italy)
- L. Gnetti (Parma, Italy)
- C. Lagrasta (Parma, Italy)
- M. Silva (Parma, Italy)
- G. Roti (Parma, Italy)
- N. Sverzellati (Parma, Italy)
- M. Tiseo (Parma, Italy)
Abstract
Background
The ground-breaking advent of immunotherapy in the oncologic arena still leaves uncovered the identification of valid prognostic and predictive biomarkers. To this aim, we advanced the hypothesis that intersecting the tumor immune microenvironment (TIME) with high-throughput extracted radiomic features may identify NSCLC patients with distinct clinical outcome.
Methods
We enrolled 60 surgically resected NSCLC patients. TIME was assessed by the quantitative evaluation of PD-L1 levels and an extensive morphometric analysis of Tumor Infiltrating Lymphocytes (TILs). From each CT scan, in addition to semantic characteristics, 841 radiomic features were extracted through an open-source (3d Slicer) software. Radiomic variables were subjected to statistical analysis to test their correlation with tissue immune profiles and survival outcome.
Results
A cluster of 3 patients (A) displaying oppositely regulated radiomic features was identified by an unsupervised hierarchical model. Compared to the remaining cases, cluster A had a significantly reduced (p < 0.01) OS (13 vs 33 mos.) and DFS (11 vs 25 mos.) and shared similar semantic imaging characteristics (no effect on parenchyma and subsolid texture) and a desertic TIME (PD-L1low and TILslow). Radiomic variables from cluster A were then compared to those extracted from patients matched for both desertic TIME and qualitative CT parameters but with favorable survival outcome (cluster B). By applying signal-to-noise ratio and T-test, the most significant oppositely regulated wavelet features (p < 0.0001) in the two clusters were Large Dependence Emphasis, Busyness, Cluster-Tendency and Gray Level Variance. The detailed analysis of corresponding TIME revealed that PD-1-to-CD8 ratio was the only immunophenotypic parameter differentially expressed by the two prognostic classes.
Conclusions
Higher order radiomic features associated with specific TILs phenotype may enclose a radiologic signature with prognostic impact on NSCLC.
Legal entity responsible for the study
University Hospital of Parma.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
42O - Implementation of organized lung cancer screening program in Korea
- Y. Kim (Goyang, Korea, Republic of)
- Y. Kim (Goyang, Korea, Republic of)
Abstract
Background
Lung cancer is the leading cause of cancer mortality worldwide and has a low survival rate due to difficulties cocnerning early detection. The Korean Lung Cancer Screening demonstration project (K-LUCAS) was started in February 2017. K-LUCAS will assess the effectiveness, harm, and feasibility of lung cancer screening in order to implement a population-based screening program. K-LUCAS will evaluate the validation of the new standard of reporting form of low-dose computed tomography (LDCT) and the quality of lung cancer screening by a web-based network system using computer-aided nodule detection program (CAD).
Methods
K-LUCAS is a population-based single arm trial conducted in 14 cancer hospitals that targets a high-risk population aged 55-74 years with at least 30 pack-year smoking history within the last 15 years. Participants were recruited when visiting the national cancer screening center or smoking cessation clinics based on a lung cancer risk evaluation questionnaire. Lung cancer screening was provided by LDCT with at least a 16-row multidetector CT scanner and screening results were reported by Lung Imaging Reporting and Data System (Lung-RADS). All participants should have their results explained to them by a physician and current smokers should receive smoking cessation counselling.
Results
Up until November 2018, 13,491 participants had joined K-LUCAS. The positive screening rate (categories 3 and 4 in Lung-RADS) was 15.3%. Among these, 69 lung cancers were detected and stage I and II lung cancers were 53.6% and 15.9%, respectively. CAD detects more positive findings but decreases the variation of positive rate among screening units. About 75% of abnormal findings, including emphysema, coronary artery calcification etc. besides lung nodules, were detected in K-LUCAS.
Conclusions
K-LUCAS shows promising results in effective detection of early stage lung cancer and controlling diagnosis quality by a web-based network system. Based on the observations from K-LUCAS, a decision will be made as to whether lung cancer screening will be included in national cancer screening program.
Clinical trial identification
NCT03394703.
Legal entity responsible for the study
The author.
Funding
Ministry of Health and Welfare, Republic of Korea.
Disclosure
The author has declared no conflicts of interest.
43O - Baseline results from a French pilot study on lung cancer screening by CT scan: DEP KP80
- O. Leleu (Abbeville, France)
- O. Leleu (Abbeville, France)
- M. Auquier (Amiens, France)
- B. Chauffert (Amiens, CEDEX, France)
- P. Berna (Amiens, France)
- V. Petigny (Amiens, France)
- A. Ait Addi (Amiens, France)
- D. Basille (Amiens, France)
- V. Jounieaux (Amiens, France)
Abstract
Background
Lung cancer is the leading cause of cancer death worldwide. Two large randomized controlled trials (NLST,NELSON) founded a significant decrease in lung cancer mortality with an annual low dose CT screening among selected current or former smockers.While being now recommended in many countries, the French National Authority for Health claimed that conditions were not sufficient for implementation of such a screening program in France. The aims of our study were to assess the feasibility and effectiveness of a lung cancer screening pilot program with LD CT scan in a French department. We report here the results of the first screening round.
Methods
DEP KP80 was a single-arm, prospective study started in May 2016 and ended in December 2018 in a French department (Somme). The inclusion criteria were those of the NLST study. An annual LD CT scan was scheduled and 2 rounds were planned. Our algorithms considered nodules<5mm as negative, nodules> 10mm as positive and recommended a 3-month CT with measurement of the doubling time for nodules between 5 and 10 mm . Smoking cessation was encouraged as part of the protocol. This study was managed by the departmental cancer screening agency (ADEMA80). All General Practitioners (GP), pulmonologists (PN) and radiologists from the department were solicited by mail to participate in this study. Subjects were selected by GP or PN who checked the inclusion criteria and precribed the CT scan.
Results
218 GP, 17 PN and 28 radiologists accepted to participate. Over a 2.5 years period, 1307 subjects were recruited. the participation rate was of 73% (949 scans were performed). Screening was negative in 733 cases (77%), positive in 54 (5.7%) and indeterminate in 162 (17%). The prevalence of a detected lung cancer was 2.5% : 24 cancers with 16 adenocarcinomas,3 squamous cell carcinomas, 1 carcinoid tumour, 2 small cell carcinomas 1 undetermined and 1 unknown. There were 2 carcinoma in situ (8%),13 Stage IA (54%), 3 Stage IIB (12%), 2 Stage IIIA (8%) and 4 Stage III B,C (17%). A surgery was performed in 20 of these patients (83%) and one patient underwent surgery for benign lesion.
Conclusions
This study demonstrates, at a regional level, the feasibility and effectiveness of an organized and structured lung cancer screening by LD CT scan in France.
Legal entity responsible for the study
O. Leleu.
Funding
La ligue contre le cancer Agence Régionale de Santé Picardie and AstraZeneca.
Disclosure
All other authors have declared no conflicts of interest.
70O - Radiomic-based quantitative CT analysis to predict the invasiveness of pure ground-glass lung adenocarcinoma
- F. Xv (Hanghzou, China)
- F. Xv (Hanghzou, China)
- W. Zhu (Hangzhou, China)
- H. Hu (Hangzhou, China)
Abstract
Background
Lung cancer is till one of the leading causes of cancer-related deaths and lung adenocarcinoma is the most common type. Compared with invasive adenocarcinoma, adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) are considered as indolent lung adenocarcinoma with good prognosis. However, AIS, MIA and even some early-stage invasive adenocarcinoma can be shown as pure ground-glass nodules on computed tomorgraphy images, which is quite difficult for clinicians to make a precise diagnosis and a suitable treatment plan. Thus, we aim to investigate the performance of radiomic-based quantitative analysis on CT images in identifying invasiveness of lung adenocarcinoma manifesting as pure ground-glass nodules.
Methods
275 lung adenocarcinoma cases with 322 pure ground-glass nodules from January 2015 to October 2017 were enrolled in this retrospective study. All lesions were resected surgically and confirmed pathologically. Clinical data like age , gender, smoking status of all cases were collected from digital medical records. Radiomic feature extraction was performed using Python with semi-automatically segmented tumor regions on CT scans which was contoured with an in-house developed plugin for 3D-Slicer. The predictive performance of the prediction models was evaluated through the receiver operating characteristic curve (ROC).
Results
Among 322 nodules, 48(15%) were Adenocarcinoma in situ (AIS), 102(32%) were minimally invasive adenocarcinoma (MIA) and 172(53%) were invasive adenocarcinoma. All nodules were divided into training and validation cohort randomly with a ratio of 2:1 to establish prediction models. The values of the area under the curve were 0.716 (95%CI:0.600∼0.832) and 0.827 (95%CI:0.729∼0.925) with the diagnostic accuracy of 59.3% and 69.1% for radiomic and combined models, respectively.
Conclusions
Radiomic model built via quantitative CT analysis can help to identify the invasiveness of lung adenocarcinoma represented as pure ground-glass nodules. Combining this model with clinical features can significantly improve its prediction performance.
Legal entity responsible for the study
Fangyi Xv.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
71O - Impact of underlying pulmonary diseases on treatment outcomes in early stage non-small cell lung cancer treated with definitive radiotherapy
- H. Kim (Seoul, Korea, Republic of)
- H. Kim (Seoul, Korea, Republic of)
- H. Yoo (Seoul, Korea, Republic of)
- H. Pyo (Seoul, Korea, Republic of)
- H. Park (Seoul, Korea, Republic of)
Abstract
Background
Current guidelines recommend definitive radiotherapy for patients with medically inoperable early stage non-small cell lung cancer (NSCLC). However, impact of underlying pulmonary diseases on survival of those patients are unclear. Especially, although the patients with COPD and lung cancer have worse prognosis than those without COPD regardless tumor stage, the impact of coexisting COPD on treatment outcome after definitive radiotherapy has not been fully investigated. Thus, we aimed to evaluate the impact of underlying chronic pulmonary disease of COPD, IPF, and CPFE on treatment outcome following definitive radiotherapy in patients with medically inoperable stage I-II NSCLC.
Methods
We retrospectively reviewed the medical records of 234 patients with stage I-II NSCLC treated with definitive radiotherapy alone at Samsung Medical Center, between January 2010 and October 2017. We compared the survival outcomes according to the presence of underlying pulmonary diseases of chronic obstructive pulmonary disease (COPD), combined pulmonary fibrosis and emphysema (CPFE), and idiopathic pulmonary fibrosis (IPF). In current study, we defined control group as non-COPD, non-CPFE, and non-IPF.
Results
Among 234 study patients, 132 (56.4%) were diagnosed with COPD, 16 (6.8%) with CPFE, and 22 (9.4%) with IPF. The median follow-up duration was 17 months (range, 1 to 92 months). The median survival of control, COPD, CPFE, and IPF groups were 32, 49, 17, and 12 months, respectively (P < 0.001). In a Cox proportional hazards analysis for factors associated with overall survival, patients with COPD showed similar risk of death (Adjusted HR, 1.314; 95% CI, 0.677-2.551; p-value= 0.419) compared to control group, while patients with IPF (Adjusted HR, 3.539; 95% CI, 1.647-7.607; p-value= 0.001) and CPFE (Adjusted HR, 2.669; 95% CI, 1.095-6.505; p-value= 0.031) showed increased risk of death.
Conclusions
Definitive radiotherapy may be a tolerable treatment for early-stage NSCLC with COPD. However, the poor survival in early-stage NSCLC patients with co-existing IPF or CPFE warrants further study to identify and develop patient selection criteria and optimal radiotherapy modality.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
72O - Multi-centre analysis of cardiac events following radical radiotherapy for lung cancer
- F. Sun (Cottingham, East Yorkshire, United Kingdom)
- F. Sun (Cottingham, East Yorkshire, United Kingdom)
- K. Banfill (Manchester, United Kingdom)
- J. Lilley (Leeds, United Kingdom)
- B. Wheller (Leeds, United Kingdom)
- L. Murray (Leeds, United Kingdom)
- A. McWilliam (Manchester, United Kingdom)
- M. Van Herk (Manchester, United Kingdom)
- A. Abravan (Manchester, United Kingdom)
- C. Faivre-Finn (Manchester, United Kingdom)
- K. Franks (Leeds, Yorkshire, United Kingdom)
Abstract
Background
Radical radiotherapy (RRT) plays an essential role in the management of early and locally advanced lung cancer. Recent studies suggest cardiac events post radiotherapy worsen survival outcome for patients. This study aims to identify risk factors which predispose patients to cardiac events post radiotherapy.
Methods
All patients who received RRT (including Stereotactic Body Radiotherapy (SBRT), radical fractionated radiotherapy and chemoradiotherapy) for lung cancer between 01/01/2010 to 30/12/2016 at 2 UK institutions have been included. Patients were excluded if they had multiple courses of radiotherapy to the chest. Individual patient clinical information has been retrieved from hospital electronic database. Patient and cancer demographics have been collected. Pre-existing cardiac conditions, Charlsons’ Co-morbidity index and Qrisk 3 scores were calculated. Post radiotherapy cardiac events were identified rom electronic patient records and time to cardiac events were calculated.
Results
600 patients have been identified so far and processed. Median follow up is 31 months. Of all patients, 29% had pre-existing cardiac conditions. 52 patients experienced cardiac events following radiotherapy, of which 37% were ischaemic events. Of patients who experienced an ischaemic event, 58% did not have a known pre-existing cardiac condition. 71% of cardiac events post RRT occurred in the first 2 years following RT. Proportionally, patients who underwent radical fractionated radiotherapy and concurrent chemoradiotherapy had the highest incidence of cardiac events. Patient characteristics of those who experienced cardiac toxicity are summarized in the table belowTotal = 52 (10%) Ischaemic events 19 (7 events lead to death – Grade 5) Pericardial(effusion) events 8 Arrhythmic events 13 Cardiac failure events 12 Pre-existing cardiac diagnosis Patients who had ischaemic events 8/19 (4 previous MI, 2 IHD, 1 arrythmia and 1 valve abnormality Patients who had pericardial events 1/8 (arrhythmia) Patients who had arrhythmic events 6/13 (2 previous MI, 2 IHD, 1 CCF, 1 CCF and arrhythmia) Patients who had CCF events 9/12 (2 previous MI, 5 IHD, 2 valvular abnormality) Sex Male = 33 Female = 19 Age Median = 73 Smoking Never smoked 0 Ex-Smoker <10 PY 0 Ex-smoker <20 PY 9 Ex-Smoker 20-40PY 15 Ex-Smoker >40 PY 9 Current Smoker 19 Charlson Score Median = 6 RT indication Adjuvant RT 4 (12.5% of all Adjuvant RT) SBRT 19 (8.7% of all SBRT) Concurrent ChemoRT 10 (14.5% of all Concurrent ChemoRT) Sequential ChemoRT 0 Radical Fractionated RT 19 (15.6% of all Radical Fractionated RT) Tumour Location Left Upper Lobe(LUL) 12 (8% of all LUL tumours) Left Lower Lobe(LLL) 11 (17% of LLL tumours) Right Upper Lobe(RUL) 16 (9% of RUL tumours) Right Middle Lobe(RML) 1 (3% of RML tumours) Right Lower Lobe(RLL) 12 (17% of RLL tumours)
Conclusions
A clinically significant proportion of patients developed cardiac toxicity following radical radiotherapy for lung cancer. Cardiac events occur much sooner after lung cancer radiotherapy than radiotherapy for breast cancer or lymphoma. Work is ongoing to identify greater number of patients and combine local data with data from national registry to aid analysis.
Legal entity responsible for the study
The authors.
Funding
Yorkshire Cancer Research.
Disclosure
All authors have declared no conflicts of interest.
86O - The effect of prophylactic cranial irradiation (PCI) for young stage III NSCLC patients: Subgroup analyses of the NVALT-11/DLCRG-02 study
- W. Witlox (Maastricht, Netherlands)
- W. Witlox (Maastricht, Netherlands)
- B. Ramaekers (Maastricht, Netherlands)
- H. Groen (Groningen, Netherlands)
- A. Dingemans (Maastricht, Netherlands)
- J. Praag (Rotterdam, Netherlands)
- J. Belderbos (Amsterdam, Netherlands)
- V. Van der Noort (Amsterdam, Netherlands)
- H. Van Tinteren (Amsterdam, Netherlands)
- M. Joore (Maastricht, Netherlands)
- D. De Ruysscher (Maastricht, Netherlands)
Abstract
Background
The NVALT-11/DLCRG-02 phase III study compared PCI to observation after chemo-radiotherapy (RT) for stage III NSCLC and showed a significant decrease in the cumulative incidence of symptomatic brain metastases (BM) in the PCI arm at two years (7% vs 27% [HR 0.23]). We here performed exploratory subgroup analyses.
Methods
Two year cumulative incidence rates were calculated and competing risk regression, with death of any cause as competing risk, was used to examine the time to symptomatic BM in the following subgroups: age, gender, performance status, disease stage and tumour type, prior surgery, chemotherapy cycles, thoracic RT dose and total concurrent chemo-RT treatment time. For continuous variables, the median was used as a cut-off value. The effect of PCI was only examined if the initial result was significant.
Results
In total, 174 patients were analysed. The symptomatic BM incidence was significantly lower in the subgroup of older (>61 years) versus younger ( = <61 years) patients (7% vs 26% [HR 0.25]). Stratified by age, PCI only significantly reduced the symptomatic BM incidence in younger patients (9% vs 42% [HR 0.18])(Table).
Conclusions
The symptomatic BM incidence was significantly lower in older (>61 years) compared to younger ( = <61 years) patients, likely due to higher numbers of adenocarcinoma in the younger patients group. The effect of PCI was only significant in younger patients. This study was randomized based on treatment allocation and subgroups might be too small to detect significant differences. Therefore, our results are hypothesis generating and should be prospectively tested.
Clinical trial identification
NCT01282437.
Legal entity responsible for the study
Nederlandse Vereniging van Artsen voor Longziekten en Tuberculose (NVALT).
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
120O - Thromboembolic events in advanced non-small cell lung cancer
- V. Srinivasalu (Bangalore, India)
- V. Srinivasalu (Bangalore, India)
- N. Subramaniam (Kochi, India)
- S. Raghuram (Kochi, India)
- S. Kolathu (Kochi, India)
- B. Ponnada (Kochi, India)
- A. Philip (Cochin, Tamil Nadu, India)
- W. Jose (Kochi, Kerala, India)
- K. Pavithran (Kochi, Kerala, India)
Abstract
Background
Cancer is a prothrombotic condition and its treatment is often complicated in the presence of thromboembolisms (TE) which adds to its morbidity and mortality. We aimed to assess the incidence of TE’s in patients with NSCLC treated at our institute.
Methods
A retrospective observational study of patients with NSCLC treated between January 2011 and December 2016 were included. Time of onset of TE’s either at diagnosis or after the start of platinum-based chemotherapy was noted, Khorana score was calculated in all patients with TE’s. A TE occurring between first dose of chemotherapy and 4 weeks after the last dose was considered to be chemotherapy associated.
Results
On analysis of records from the EMR, we found a total of 1542 NSCLC patients who were treated at our institute, with a male to female ratio of 3.5 : 1. All patients with TE’s had stage IV disease at the time of presentation. Fifty-nine (3.8%) patients out of 1542 developed TE’s, 53 had venous TE and 6 had cerebral arterial infarction. Twenty-five (1.6%) had TE’s at the time of diagnosis while 34 (2.9%) out of 1180 developed TE while on treatment with platinum based chemotherapy. The mean age was 60 years (Range:34-81 yrs) with a male predominance (59%). Majority of patients developed TE’s within 100 days from the start of chemotherapy with a median time of 66 days. (Range:14-143 days) Intermediate and high risk groups on assessment of Khorana score was 61% and 39% respectively. The median overall survival for patients with TE was 129 days in comparison to 234 days for patients without thromboembolisms.
Conclusions
Thromboembolism is associated with a poor prognosis in patients with advanced lung cancer. Patients receiving platinum-based chemotherapy are predisposed to higher incidences of thromboembolic events which raises a valid question of the need of thromboprophylaxis in a selected group of patients.
Clinical trial identification
It is not a clinical trial
Legal entity responsible for the study
Amrita Institute of Medical Science.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.