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V. Anikin



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    O11 - Symptom Management (ID 137)

    • Event: WCLC 2013
    • Type: Oral Abstract Session
    • Track: Supportive Care
    • Presentations: 1
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      O11.07 - Tracheobronchial Stent Insertion in the Management of Primary Lung Cancer: 5 Year Experience (ID 818)

      16:15 - 17:45  |  Author(s): V. Anikin

      • Abstract
      • Presentation
      • Slides

      Background
      Central airway obstruction is seen in around 30% of patients with primary lung cancer. This is often a life-threatening presentation of the disease due to imminent airway loss and therefore requires urgent intervention. Direct bronchoscopic techniques including airway stenting can offer an immediate improvement in symptoms and quality of life, in addition to providing time for further treatment modalities. Here we report outcomes from a large single centre five year experience of tracheobronchial stent insertion for palliation of advanced primary lung cancer.

      Methods
      A retrospective review of all patients undergoing tracheobronchial stent insertion between January 2007 and January 2012 was performed. Patients undergoing stent insertion for benign or secondary malignant disease were excluded. A total of 70 patients underwent 80 stenting procedures with an average age of 66 years. Patient notes were used to collect patient demographic, disease and stenting data. Outcomes included post-procedure length of stay, complications, need for further intervention and overall survival.

      Results
      Disease was identified within the trachea in 18 cases, bilaterally within the bronchi in 10 cases and in the left or right bronchus in 23 and 28 cases respectively. Expandable, nitinol stents were used for all patients with either a proximal or distal release system. Uncovered stents (57), covered stents (20) or a mixture of the two (3) were placed. The average length of stay was 2.5 days (range 0-17); however, 69% of patients were discharged on the same day or on day one following the procedure. There were no cases of stent migration identified. The most common complication was retained secretions requiring repeat bronchoscopy which occurred in 5 cases. One patient required telescopic insertion of a second stent due to malposition of the first. Median survival was 2.6 months with a 20% one-year survival. There were 4 in hospital deaths.

      Conclusion
      Central airway obstruction secondary to primary lung cancer can cause disabling dyspnoea and impending suffocation. Interventional bronchoscopic techniques, in particular airway stenting, can provide immediate relief of these symptoms. The survival data here reflects the advanced stage of disease in this patient group and, although unlikely to improve survival, airway stenting can offer the opportunity for further adjuvant treatment in some cases. More importantly perhaps, 91% of patients were discharged home following the procedure allowing an improved in quality of life. In our experience, tracheobronchial stent insertion can be used effectively to achieve these outcomes with minimal complications and a short hospital admission. Figure 1

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    P1.03 - Poster Session 1 - Technology and Novel Development (ID 150)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P1.03-006 - The efficiency of detection of <em>KRAS</em>, <em>EGFR </em>and <em>BRAF </em>mutations in primary lung cancer via peripheral blood circulating tumour cells (ID 2762)

      09:30 - 16:30  |  Author(s): V. Anikin

      • Abstract

      Background
      Circulating tumour cells (CTCs) are present in the blood of a proportion of patients with lung cancer. However, it is currently unclear how suitable CTCs are for use in the detection of predictive genetic mutations. We sought to determine the utility of DNA extracted from CTCs to screen for the underlying primary tumour mutation.

      Methods
      Using ScreenCell™ MB devices, from 20/01/12 to 25/01/2013, CTCs were captured in peripheral blood of 100 patients who underwent surgery for lung cancer at The Royal Brompton Hospital. DNA was extracted using QIAamp DNA Micro kit (QIAGEN) followed by whole-genome amplification using GenomePlex® SingleCell WGA kit (Sigma). DNA from matched primary tumours was used as reference. Mutation detection in EGFR and KRAS genes was undertaken using cobas®4800 (Roche) and single-strand conformation analysis for BRAF gene. Sensitivity and specificity analyses were undertaken to measure predictive performance of mutation testing in CTCs.

      Results
      The DNA extracted from CTCs, were of sufficient quality to allow mutation analyses to be successfully performed in 100%, 99%, and 98% of samples for EGFR, KRAS, and BRAF genes, respectively. In CTC DNA, the KRAS mutation rate (codons 12/13 and 61) was 9.1% and concordance with the primary tumour was 78.8%. Six mutations were detected in CTCs, but not in primary tumours, and 13 mutations in primary tumours were not detected in corresponding CTC samples. Three mutations were detected in matched CTC and primary tumour specimens. One mutation in EGFR was detected in CTC DNA and 3 mutations were detected in primary tumours. In all cases, the mutations were detected in discordant specimens. The concordance between mutations detection in CTCs and primary tumours was 95.8%. BRAF V600E mutation was not detected in any sample. In general, the results suggested low sensitivity but high specificity (Table). Due to low number of EGFR mutations detected, test performance results require further validation.

      The performance of mutation testing in circulating tumour cells
      Statistic KRAS EGFR
      Sensitivity (95% CI), % 18.8 (4.05-45.6) 0.0 (0.0-70.8)
      Specificity (95% CI), % 91.8 (83.0-96.9) 98.9 (94.1-100)
      Positive predictive value (95% CI), % 33.3 (7.49-70.1) 0.0 (0.0-97.5)
      Negative predictive value (95% CI), % 83.8 (73.8-91.1) 96.8 (91.0-99.3)

      Conclusion
      The result of our study indicates that the DNA extracted from CTCs can be used to screen for primary tumour mutations with reasonable concordance. Differences in the mutation results from the CTC and primary tumours needs to be explored in more detail and may be due to issues related to processing and / or tumour versus CTC heterogeneity.

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    P2.24 - Poster Session 2 - Supportive Care (ID 157)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Supportive Care
    • Presentations: 1
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      P2.24-020 - Uk Lung Cancer Survival: Where are we going wrong? (ID 1363)

      09:30 - 16:30  |  Author(s): V. Anikin

      • Abstract

      Background
      A number of recent studies have reported poor cancer survival in England when compared to other developed countries worldwide. In particular, lung cancer has been highlighted as amongst the worst, with only Scotland and Malta showing poorer survival rates in Europe. The aim of this study was look for an explanation for these findings by assessing our post-operative survival in patients undergoing surgery for lung cancer. Through this we hope to establish whether the management of patients with curative disease is inferior or whether other key factors, such as stage and timing of diagnosis, are to blame.

      Methods
      501 patients were identified who had undergone lobectomy, bilobectomy or pneumonectomy for non-small cell lung cancer between January 2003 and January 2011. Information regarding patient demographics and histological stage of disease was collected. NHS number tracing was used to obtain patient status at follow-up. Survival data was plotted using the Kaplan-Meier method with comparison of stage 1 and 2 disease. In addition, information was collected from the NHS lung cancer database to identify the percentage of patients diagnosed with non-small cell lung cancer who underwent surgical management during the research period.

      Results
      Of the 501 patients within this cohort, 263 had stage 1 disease, 147 stage 2 disease and 91 stage 3 or 4 disease. Average age at the time of surgery was comparable between the groups (mean 67 years) and there were considerably more men within the study than women (M:F = 303:198). 5 year survival in patients with stage 1 or 2 disease was 75% or 40% respectively (Figure 1). On average, 12.9% of patients diagnosed with NSCLC underwent surgical resection. Figure 1: Comparison of survival following lung resection in patients with stage 1 and 2 NSCLC Figure 1

      Conclusion
      Cancer survival is an important measure of the effectiveness of both management strategies and healthcare systems. These findings demonstrate that in patients with early, operable lung cancers we are achieving survival rates comparable, and in some cases superior, to other developed countries. Only a very small number, 12.9% of patients, are diagnosed early enough to undergo surgery. This would suggest that it is not the treatment provided in England that is inferior, but our ability to diagnose lung cancer at an early stage.

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    P3.20 - Poster Session 3 - Early Detection and Screening (ID 174)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Imaging, Staging & Screening
    • Presentations: 1
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      P3.20-009 - Diagnostic performance of a filter-based antibody-independent peripheral blood circulating tumour cell capture paired with cytomorphologic criteria for the diagnosis of lung cancer (ID 2782)

      09:30 - 16:30  |  Author(s): V. Anikin

      • Abstract

      Background
      The ability to capture and characterise peripheral blood circulating tumour cells (CTCs) has the potential for the development of a blood test for cancer. A number of technological platforms are available to obtain CTCs including filtration-based devices utilising advances of antibody independent capture of cells. This technique shows promising results in experimental conditions; however, its performance has not yet been well evaluated in a clinical setting. We have evaluated diagnostic performance of filtration-based technology using cytomorphologic criteria in patients undergoing surgery for lung cancer.

      Methods
      From 06/03/2012 to 24/01/2013 we obtained and processed blood from 74 patients undergoing surgery for known or suspected lung cancer using ScreenCell[TM] Cyto devices. Captured cells were stained using H&E and independently assessed by two pathologists (AGN, AR) for the presence of atypical cells suspicious for cancer. Results were reported as confirmed cancer, suspicious or no evidence for cancer. Diagnostic performance was evaluated against the reference of cancer identified within surgically obtained specimens reported by a principal pathologist. Sensitivity and specificity analyses were undertaken. Inter-observer agreement was established by kappa-statistics.

      Results
      According to histopathology assessment, 42 patients (56.7%) had primary lung cancer, 18 patients (24.3%) had metastatic cancer (predominantly of colorectal origin), and 14 patients (18.9%) had benign lung diseases. The proportion of patients in which cells suspicious for cancer were identified was 39 (52.7%) and 42 (56.7%) as reported by two pathologists. Among those cases, 6 (15.4%) and 14 (33.3%) were reported as confirmatory. The agreement between the pathologists was 77% corresponding to a kappa-statistics of 53.7% indicating moderate agreement. In metastatic cancer patients, suspicious cells were discovered in 10 (55.6%) and 9 (50%) cases by two pathologists. In non-cancer patients, suspicious cell were found in 6 (42.8%) and 5 (35.7%) cases by two pathologists, respectively. The test performance for the diagnosis of cancer using cytomorphological criteria yielded poor-to-moderate sensitivity and specificity values, high positive predictive values and low negative predictive values (Table).

      The performance of the diagnosis of cancer using filter-based antibody-independent technique of CTCs trapping
      Statistic Pathologist 1 Pathologist 2
      Sensitivity (95% CI), % 55.0 (41.6-67.9) 61.7 (48.2-73.9)
      Specificity (95% CI), % 57.1 (28.9-82.3) 64.3 (35.1-87.2)
      Positive Predictive Value (95% CI), % 84.6 (69.5-94.1) 88.1 (74.4-96.0)
      Negative Predictive Value (95% CI), %
      		22.9 (10.4-40.1) 28.1 (13.7-46.7)

      Conclusion
      The results of our study highlight the potential of filter-based antibody-independent technology to develop an accurate blood test for the diagnosis of cancer in the peripheral blood. However, conventional cytomorphological criteria used for the diagnosis provide inadequate sensitivity and specificity. Improved performance with immunocytochemistry is still required prior to further clinical validation.