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C. Dooms



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    MO10 - Molecular Pathology II (ID 127)

    • Event: WCLC 2013
    • Type: Mini Oral Abstract Session
    • Track: Pathology
    • Presentations: 1
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      MO10.07 - ALK immunohistochemistry and fluorescence in-situ hybridization in Lung adenocarcinomas from the ETOP Lungscape tumour cohort (ID 2267)

      16:50 - 16:55  |  Author(s): C. Dooms

      • Abstract
      • Presentation
      • Slides

      Background
      The European Thoracic Oncology Platform LungScape database contains 2614 cases of primary resected lung carcinoma from 16 centres with patient demographics, pathological tumour data and detailed clinical follow-up. A total of 1281 cases of adenocarcinoma with >2 years clinical follow-up were selected for analysis of ALK status by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Test positive cases were matched, in order of importance at ratio 1:2, by stage, gender, smoking status, study centre, year of surgery and age with test negative cases -both for IHC and for FISH testing.

      Methods
      Testing was performed in all centres using the same protocol (IHC: Novocastra 5A4 clone antibody at 1:10 dilution, Novolink detection system. FISH: Abbott Vysis ALK break-apart probe). Each centre passed an external QA test using unknown cases in a tissue microarray before conducting the LungScape tumour testing. IHC was scored according to three intensity scores (1+, 2+, 3+) using ‘objective’ methodology previously described [1]. Maximum staining intensity was recorded. Any IHC staining was defined as IHC positive result. FISH preparations were assessed according to the Vysis protocol on all 82 IHCpositive cases plus their 164 IHCnegative matches.

      Results

      IHC cases, n=1281 FISH positive(264 tested)
      IHC negative 1199 (93.6%) 0 (0.0% of 164 controls) FISH specificity: 100%
      IHC 1+ 43 (3.35%) 2 (4.6% of IHC 1+)
      IHC 2+ 16 (1.25%) 6 (37.5% of IHC 2+)
      IHC 3+ 23 (1.8%) 20 (87% of IHC 3+)
      IHC any positive 82 (6.4%) 28 (34.1% of IHC+) FISH sensitivity: 34.1%
      FISH sensitivity was 87% for IHC 3+. IHCpositive/FISHnegative cases (n=54) were mostly IHC 1+ (75.9%), sometimes IHC 2+ (18.5%) and rarely IHC 3+ (5.5%). The frequency of never smokers was higher in the ALK IHCpositive group (29.3%) versus IHCnegative group (18.3%) {p=0.011}. Age, gender and tumour stage did not differ between IHC groups. The hazard of an event for IHCpositive cases decreases by 32% in relapse-free survival {RFS; p=0.03} and by 38% in either time-to-relapse {TTR; p=0.02} or overall survival {OS; p=0.016}. Multivariate models -adjusted for patient and tumour characteristics- indicated that IHC-ALK was a significant predictor for all three time-to-event outcomes (RFS, TTR, OS). In stratified Cox analysis, significantly higher OS was retained in the IHCpositive (HR=0.59, p=0.04) and FISHpositive (HR=0.34, p=0.03) cases in the matched cohorts, while conditional logistic regression yielded non-significant associations with 3-year survival status.

      Conclusion
      In this large cohort of surgically resected primary lung adenocarcinoma: ALK IHC positivity was 6.4%. IHC 3+ staining (prevalence 1.8%) showed 87% probability of ALK FISH positivity ALK IHC positivity was higher in never smokers and related to better clinical outcome ALK testing can be reliably implemented across multiple laboratories {1} Ruschoff et al. Virchows Arch. 2010;457(299-307).

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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): C. Dooms

      • 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.