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K. Nackaerts



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    MO23 - Radiotherapy II: Lung Toxicity, Target Definition and Quality Assurance (ID 107)

    • Event: WCLC 2013
    • Type: Mini Oral Abstract Session
    • Track: Radiation Oncology + Radiotherapy
    • Presentations: 1
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      MO23.10 - Addition of EBUS-mapping of the mediastinum to PET/CT based selective nodal irradiation in NSCLC decreases geographical miss and nodal GTV volume (ID 2841)

      11:25 - 11:30  |  Author(s): K. Nackaerts

      • Abstract
      • Presentation
      • Slides

      Background
      FDG-PET/CT based selective lymph node (LN) irradiation is the standard when using 3D-conformal techniques (3D-CRT) for locally advanced NSCLC. With 3D-CRT, adjacent LN not included in the target volume still receive a substantial radiation dose. With current new techniques (IMRT/VMAT), the radiation dose to non-involved LN decreases, which raises the question whether selective nodal irradiation based on PET/CT is still safe. We therefore evaluated the impact of adding EBUS-TBNA (endobronchial ultrasound guided transbronchial needle aspiration)-mapping of the mediastinal LN to PET/CT in avoiding geographical miss, and on the size of nodal GTV (gross tumor volume).

      Methods
      Consecutive NSCLC-patients referred for radiotherapy (RT) in 2012 who underwent EBUS-TBNA were included. False negative (FN) LN for different constellations of PET, CT and EBUS-TBNA based on literature data were calculated, to evaluate the safety of excluding LNs based on CT, PET and EBUS findings. A practical algorithm when to include LN in the GTV was made, and tested on our patients. Results are expressed as mean +/- SD and range.

      Results
      Twenty-five consecutive patients with a full EBUS-TBNA mapping before RT were included: 11 women, 14 men; 17 adenocarcinoma, 8 squamous cell carcinoma; 14 right-sided and 11 left-sided tumors. Mean age: 62.5 +/- 9.7 years. All patients had stage III-disease based on PET-CT. LN stations 1,2R,2L,3,4R,4L,5,6,7,8,9,10-11L,10-11R were analyzed on CT- and PET-scan (=325 LN). Sixty-seven were enlarged (≥10mm), of which 63 were PET-positive. Twelve normal-sized LNs were PET-positive. Fifty LNs were investigated with EBUS-TBNA (mean: 2/patient +/-0.96;1-5): 28 were malignant, 22 normal. EBUS-TBNA detected 1 cancer-containing normal-sized LN without FDG-uptake, thus 1/25 geographical miss (4%). The cancer prevalence, taking into account the FN rate of EBUS of 20%, was calculated (Fig.1). With addition of EBUS, in PET-negative patients FN decreases with 10% for enlarged LN, and with 5% for normal-sized LN. An algorithm when to include a LN in the GTV is proposed (Fig.1). According to this algorithm, in our population 3/79 (4%) enlarged or PET-positive LN would be excluded from the GTV. At patient level, this was a GTV decrease in 3 (12%) patients.

      Conclusion
      When incidental nodal irradiation is low such as in IMRT or VMAT, EBUS-TBNA should be added to FDG-PET/CT for mediastinal staging. This avoids geographical miss in 4% of patients, and decreases the radiation volume in 12% of patients. A practical algorithm is proposed.

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    O26 - Support and Palliation II (ID 140)

    • Event: WCLC 2013
    • Type: Oral Abstract Session
    • Track: Nurses
    • Presentations: 1
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      O26.06 - Impact of geriatric assessment on treatment decisions in older lung cancer patients. (ID 1419)

      17:10 - 17:20  |  Author(s): K. Nackaerts

      • Abstract
      • Presentation
      • Slides

      Background
      This study aims to investigate the influence of a geriatric assessment (GA) on cancer treatment decisions in older lung cancer patients (pts). We also studied the changes in functionality during treatment and the occurrence of severe chemotherapy-related toxicity.

      Methods
      For this analysis, we selected the lung cancer cohort that was part of a larger study on GA in older cancer pts in 6 tumor types in two Belgian university hospitals[1]. Between July 2009 and September 2011, pts aged 70 years or older with a newly diagnosed or progressive lung cancer were evaluated at baseline using a uniform GA including geriatric screening with G8 and the Flemish Triage Risk Screening Tool (fTRST), pain, social data, Activities of Daily Living (ADL), Instrumental Activities of Daily Living (IADL), fall history, Mobility-Tiredness Test (MOB-T), Mini Mental State Examination (MMSE), Geriatric Depression Scale (GDS-15), Mini Nutritional Assessment (MNA), ECOG-Performance Status (ECOG-PS), Charlson Comorbidity Index (CCI) and poly-pharmacy assessment. GA results were communicated to the treating physician and, after the treatment decision, the physician was interviewed using a predefined questionnaire focusing on unknown geriatric problems revealed by GA and impact on cancer treatment decisions. Between two and three months of follow-up, functionality was reassessed and severe toxicity in pts receiving chemotherapy was recorded.

      Results
      Seventy three lung cancer pts were included with a median age of 76 years; 82.2% were non-small cell lung cancer (NSCLC) and 74% were stage IV. Treatment was modified from standard according to standard clinical assessment (including age) in 56.1%. GA revealed unknown geriatric problems in 25.8% of cases, leading to a geriatric intervention in 10.6%. 30% of physicians consulted the GA before final treatment decision and in three pts (4%) only this led to a modification of the proposed treatment: dose reduction, no chemotherapy or no radiotherapy. At follow up (n=50), functional decline was observed in 24% and 54% of pts for ADL and IADL, respectively. Grade III-IV toxicity occurred in 14/42 pts treated with chemotherapy (33%), mainly non-haematological (64%).

      Conclusion
      This analysis indicates that the treatment of older lung cancer pts is often influenced (deviated from standard) by standard clinical assessment and age. Although GA revealed previously unknown information in 25.8% of pts, only a minority of physicians consulted these results before the final cancer treatment decision. There was little impact on geriatric intervention and even less on cancer treatment decision. This discrepancy reveals the need to get physicians treating lung cancer acquainted with GA and geriatric interventions in an attempt to decrease chemotherapy related toxicity and improve quality of care. Further evaluation of GA and geriatric interventions in larger pt groups as well as their implementation in clinical practice is warranted.

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    P1.25 - Poster Session 1 - Nurses (ID 248)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Nurses
    • Presentations: 1
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      P1.25-003 - Characteristics and outcome of unplanned admissions in patients with lung cancer: A longitudinal tertiary center study. (ID 1911)

      09:30 - 09:30  |  Author(s): K. Nackaerts

      • Abstract

      Background
      Unplanned hospital admissions (UHAs) are frequent in lung cancer patients, but literature on this topic is scarce. The aim of this study is to get better insight in the demographics, patterns of referral, presenting symptoms, and outcome of lung cancer patients with UHA.

      Methods
      Data of all consecutive events of UHA between July 1 and December 31, 2012 were reviewed. Details on the factors listed above were examined.

      Results
      There were 247 UHA events during the 6 month study period. Male/female ratio was 185/62, mean age was 66 years (range 40-90), PS on admission was 0-1 in 79 (32%), 2 in 92 (37%), and 3-4 in 76 (31%). Two thirds were stage IV, and 57% did not have ongoing oncological treatment. On 83 occasions (34%), referral was by the general practitioner (GP-REF), for 101 (41%) own initiative (SELF-REF), and for 63 (26%) specialist advice. The most frequent main presenting symptoms were respiratory (21%), infection (15%), general weakness (15%), and pain (13%). The mean hospitalization duration was 9.5 days, shorter and with more same-day-return in SELF-REF patients (Table). Final diagnoses were categorized in nine groups: infection (22%), respiratory problems (17%), lab abnormalities (13%), pain (12%), abdominal problems (11%), cardiovascular problems, neurological events, general weakness and other (6% each). This differed from the problem as recorded in the ER in one third of the events. Final grading (CTC AE v3.0) of the main event was 1-2 in 38%, 3 in 51%, 4 in 8% and 5 in 2%. Causality was decided as therapy-related (THER-REL) in 59, cancer-related (CANC-REL) in 117, unrelated in 48, and unclear in 23. In the THER-REL events, lab abnormalities (36%), infection (34%) and abdominal complaints (22%) were most common, while this was respiratory problems (23%), pain (18%) and infection (16 %) for CANC-REL events. On subgroup analysis (Table), length of stay was higher in CANC-REL events. Nearly all THER-REL events had medical therapy, while for CANC-REL events this was medical 50%, interventional 33% and supportive only 17%. Figure 1

      Conclusion
      UHA in lung cancer are predominantly cancer- rather than therapy-related, with a variety of symptoms. More than half of the events are not seen by the GP first, and the majority results in hospital stay of 9.5 days on average . Our work is a first step in identifying specific groups of events, where better interaction with GPs and education of patients might reduce the incidence of UHAs.

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    P2.04 - Poster Session 2 - Tumor Immunology (ID 154)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P2.04-002 - Differential expression of PD-L1, PD1 and CTLA4 receptor according to histology and tumour vs. surrounding non-malignant lung tissue in non-small cell lung cancer: RNA sequencing data (ID 2427)

      10:30 - 11:30  |  Author(s): K. Nackaerts

      • Abstract

      Background
      Immune modulatory strategies directed against CTLA4 (Cytotoxic T-Lymphocyte Antigen 4), PD1(Programmed cell Death 1) and PD-L1 (Programmed cell Death 1 Ligand 1) either in monotherapy or in combination with chemotherapy and radiotherapy offer great promise as novel treatments against lung cancer. Its outcome and therapeutic ratio may depend on the expression of the target molecules in tumours and the surrounding non-malignant lung tissue. We here report the expression of CTLA4, PD1 and PD-L1 in primary resected NSCLC and in the surrounding non-malignant lung.

      Methods
      RNA sequencing was performed on tumor tissue and normal lung tissue from resection specimens of NSCLC patients. The association between CTLA4, PD1 and PD-L1 expression levels and histology, gender, age, smoking status (current smoker vs. smoking cessation of at least one year), COPD and CRP blood levels was calculated both in the primary tumour and the normal lung. Results are expressed as mean +/- SD and range. Means were compared using Wilcoxon’s signed rank test for the distributions were non-parametrical. P-values <0.05 were considered significant.

      Results
      Fourteen patients were studied, 11 males and 3 females, with a mean age of 64.6 +/- 10.0 years (41-79). All patients had a smoking history: 6 were current smokers, 8 former smokers. COPD status: 8 no COPD, 1 GOLD class I, 3 GOLD class II, 2 GOLD class III. Pre-operative CRP (mg/dL): 15.0 +/- 2.9 (0.20-54.7). Seven patients had squamous cell cancer, 7 adenocarcinoma. PD-L1 expression in the lung was 3833 +/- 787 (372-5072), PD-L1 in the tumour 2595 +/- 1657 (788-6689), with a tumour/lung ratio of 0.67 +/- 0.37 (0.21-1.32). PD-L1 squamous vs. adenocarcinoma was 1840 +/- 1012 vs. 3350 +/- 1896, p<0.001. PD-L1 in the lung of ex-smokers vs. current smokers: 4136 +/- 811 vs. 3430 ± 591, p<0.001. These associations were not found for CTLA4 and PD1 receptor: CTLA4 tumour squamous vs. adenocarcinoma: 100.9 +/- 46.3 vs. 95.3 +/- 73.6, p=0.86; CTLA4 lung smokers vs. ex-smokers: 78.4 +/- 41.3 vs. 107.0 +/- 75.1, p=0.75. PD1 receptor tumour squamous vs. adenocarcinoma: 591 +/- 244 vs. 689 +/- 263, p=0.31 PD1 receptor in the lung of smokers vs. ex-smokers: 599 +/- 278 vs. 695 +/-216, p=0.46. No associations between CTLA4, PD1 and PD-L1 in the tumour or the lung and gender, age, COPD and CRP blood levels were found.

      Conclusion
      RNA sequencing is a useful method to dissect relevant molecules in the tumour and the lungs. Our results show more PD-L1 expression in adenocarcinoma than in squamous cell cancer, more PD-L1 expression in the non-malignant lung of ex-smokers than in current smokers and reduced PD-L1 in tumours compared to adjacent lung tissue.

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    P3.14 - Poster Session 3 - Mesothelioma (ID 197)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Mesothelioma
    • Presentations: 1
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      P3.14-003 - Volatile Organic Compounds as diagnostic tool for Malignant Pleural Mesothelioma. (ID 709)

      09:30 - 09:30  |  Author(s): K. Nackaerts

      • Abstract

      Background
      Early diagnosis of malignant pleural mesothelioma (MPM) can improve patients’ outcome but is hampered by non-specific symptoms and investigations, which delay diagnosis and result in advanced stage disease [van Meerbeeck JP, 2011]. An accurate non-invasive test allowing early stage diagnosis in asbestos-exposed persons is lacking. Breathomics aims at a non-invasive analysis of volatile organic compounds (VOCs) reflecting the cells’ metabolism. The breathogram obtained by the electronic nose does however, not allow identification of MPM-related VOCs [Chapman EA 2009, Dragonieri S 2011]. Ion mobility spectrometry (IMS) combines the advantages of online direct sampling with the possibility of VOC identification and linking to MPM pathogenesis [Baumbach JI 2009]. We investigated which VOCs could play a role in MPM pathogenesis in order to build a possible diagnostic MPM tool.

      Methods
      10 MPM patients and 10 healthy asbestos-exposed individuals (mean asbestos fiberyear count 14,6 (5,5) fibre.years/cc) were included after refraining from eating, drinking and smoking for at least 2 hours before sampling. They breathed tidally for 3 minutes through a mouthpiece connected to a bacteria filter. Ten ml alveolar air was sampled via a CO~2-~controlled ultrasonic sensor and analyzed using the BioScout Multicapillary Column/Ion Mobility Spectrometer (MCC/IMS, B&S Analytik, Dortmund, Germany) [Westhoff M 2009], by using N~2~ as a carrier gas. Per subject a background sample was taken. Peaks of interest were visually selected and their intensity (V) was analyzed and compared between background and breath samples via on-board VisualNow 3.2 software and SPSS v21 (IBM) using Mann-Whitney-U tests.

      Results
      Out of 41 peaks of interest, three show a significantly higher intensity in the exhaled breath of MPM patients than healthy controls [Table]. The high AUC~ROC~ of resp. P12 (0.877) and P24 (0.863) suggests a possible role of these associated VOCs in MPM pathogenesis and as a diagnostic marker in discriminating MPM patients from asbestos-exposed healthy controls. Figure 1

      Conclusion
      Several VOCs of interest were obtained in the breath of MPM patients. Two peaks were significantly discriminating between both populations. GC-MS analysis and further large cohort studies are ongoing in order to validate the accuracy of IMS as a diagnostic tool for MPM.