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M.E. Cufari



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    MINI 01 - Pathology (ID 93)

    • Event: WCLC 2015
    • Type: Mini Oral
    • Track: Biology, Pathology, and Molecular Testing
    • Presentations: 1
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      MINI01.02 - Is It Possible to Distinguish between Second Primary vs Metastasis in Resectable Synchronous Nodules with the Same Histotype of Lung Cancer? (ID 2122)

      10:45 - 12:15  |  Author(s): M.E. Cufari

      • Abstract
      • Presentation
      • Slides

      Background:
      The prognostic significance of additional lung nodules in the setting of lung cancer is important as the impact on survival is often considered for the justification of surgical selection in the management of patients with synchronous nodules. TNM 7 down staged the impact on T category but did not distinguish between second primary versus metastasis. Traditional distinctions such as the Martini criteria do not take the same histological type into account and classification continues to improve (e.g. IASLC classification of adenocarcinoma). The aim of our study is to determine if it is possible to distinguish between second primary versus metastases in patients with the same histological type and quantity any difference in survival.

      Methods:
      We retrospectively analysed data from a prospectively collated database at our institution. We collected all the records which included two resected nodules. The detailed pathology reports of these patients were retrieved and the histology, subtype and pTNM of tumours documented. Slides were re-reviewed to determine the histological subtypes according to the current IASLC adenocarcinoma classification. Survival was calculated using Kaplan Meier methods and adjusted survival compared using Cox regression on R (statistical software).

      Results:
      From April 1999 to February 2013, a total of 2925 lung cancer resection were performed. Of these, 379 (14%) operations fulfilled the inclusion criteria of multiple nodules with 316 having synchronous tumours (83.3%) and 63 having metachronous tumours (16.6%). The tumours were ipsilateral in 87.3% and the vast majority were in the same lobe (70.9%). For synchronous tumours, patients with the same histological type had a poorer 5-years survival rate compared to tumours with different histology (p=0.041). The pathologist’s designation between second primary versus intra-pulmonary metastasis distinguished between overall survival (p= 0.001) and this remained statistically significant in the tumours of the same cell type (p= 0.035). Figure 1. Survival outcomes between patients with multiple nodules classified as second primary versus intra-pulmonary metastasis Figure 1



      Conclusion:
      Our results suggest that distinction between second primary and intra-pulmonary metastasis remains important for staging as appreciable differences in survival were observed in patients with synchronous nodules. Survival was poorer in patients with multiple nodules of the same histologic type (compared to different histology) and within the same histological subtype it is possible for pathologists to distinguish between second primary and intra-pulmonary metastasis. As this is currently confirmed only on pathologic stage in the majority, it presently does not influence the selection for surgery.

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    MINI 19 - Surgical Topics in Localized NSCLC (ID 138)

    • Event: WCLC 2015
    • Type: Mini Oral
    • Track: Treatment of Localized Disease - NSCLC
    • Presentations: 1
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      MINI19.06 - External Validation of a Chinese Developed Survival Score in a Western Cohort Undergoing Surgery for Non-Small Cell Lung Cancer (ID 2226)

      16:45 - 18:15  |  Author(s): M.E. Cufari

      • Abstract
      • Presentation
      • Slides

      Background:
      Currently adjuvant chemotherapy is not recommended for patients with completely resected stage I lung cancer. The ability to sub-stratify survival within stage I is an important consideration as it is assumed that survival is heterogeneous within this sub-group. Liang et al recently published a Chinese multi-institutional logistic regression derived model to predict post-operative survival in over 5000 patients undergoing lung cancer surgery for all stages. The aim of our study is external validation of their published nomogram in a British cohort focusing on stages IA and IB to determine applicability in selection of adjuvant chemotherapy within stage I.

      Methods:
      We retrospectively analysed data from a prospectively collected database from our institutions. Patient variables were extracted and the score individually calculated. Receiver operative characteristics curve (ROC) was calculated and compared with the original derivation cohort and the discriminatory ability was further quantified using survival plots by splitting our (external) validation cohort into three tertiles and Kaplan Meier plots were constructed and individual curves tested using Cox regression analysis on Stata 13 and R 3.1.2 respectively.

      Results:
      From April 2007 to February 2015 a total of 1442 patients underwent surgery for primary lung cancer at our institution. We excluded 118 patients with carcinoid tumours (not in the original Chinese development set) and 86 patients without complete lymph node assessment leaving 1238 patients for validation. For all patients from stage IA to IIB the mean (SD) score was 9.95 (4.2). The ROC score comparing patients who died versus those that remained alive was 0.62 (95% CI 0.58 to 0.67). This was lower than the 0.71 reported by the Chinese group when split into 1,3 and 5 year survival. When divided into prognostic score tertiles, survival discrimination remained evident for the entire cohort, as well as those for stage IA and IB alone. The P value comparing survival between the middle and highest score with baseline (low score) was P=0.031 and P=0.034 respectively. Figure 1. Survival discrimination within Stage I Figure 1



      Conclusion:
      Our results of external validation suggested lower survival discrimination than reported by the original group, however discrimination between survival remained evident for stage I.

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    ORAL 24 - CT Detected Nodules - Predicting Biological Outcome (ID 122)

    • Event: WCLC 2015
    • Type: Oral Session
    • Track: Screening and Early Detection
    • Presentations: 1
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      ORAL24.03 - Increasing Incidence of Non-Smoking Lung Cancer: Presentation of Patients with Early Disease to a Tertiary Institution in the UK (ID 2717)

      10:45 - 12:15  |  Author(s): M.E. Cufari

      • Abstract
      • Presentation
      • Slides

      Background:
      Lung cancer in never-smokers is recognised as a distinct entity. Many are expected to present late. As there are no established aetiological factors, identification of patients at risk is challenging. The aim of the study is to define the incidence and clinical features of never-smokers presenting sufficiently early for surgery to determine if it is possible to identify patients at risk.

      Methods:
      We retrospectively analysed data from a prospectively collected database of patients who underwent surgery at our institution. The incidence was defined as number of never-smokers versus current and ex-smokers by year. Clinical features at presentation were obtained and collated as frequency (percentage).

      Results:
      A total of 2170 patients underwent surgical resection for lung cancer from March 2008 to November 2014. The annual incidence of developing lung cancer in never-smokers increased from 13, 15, 18, 19, 20, 20 to 28 percent respectively, attributable to an absolute increase in number and not a change in the ratio of never smokers to current and ex-smokers. A total of 436 (20%) patients were never smokers. The mean age at presentation was 60 (16 SD) years and 295 (67%) were female. Good lung function was observed with mean predicted FEV1 of 90% (23 SD) and FVC of 97% (25 SD). The majority histological types were adenocarcinoma 54% and carcinoid 27%. The main presenting features were non-specific consisting of cough in 142 (34%), chest infections in 75 (18%) and haemoptysis in 46 (11%). Recurrent chest infections were predominantly a symptom of central carcinoid tumours (30 versus 15 percent; P=0.004). A total of 59 (14%) were detected on incidental chest film, 127 (30%) on incidental CT, 32 (7%) on incidental PET/CT and 4(1%) on incidental MRI.

      Conclusion:
      We observed more than double the annual incidence of never smokers presenting with non small cell lung cancer, in the last 7 years, increasing from 13 to 28 percent, and hypothesise that this is representative of the UK, as we are one of the highest surgical volume centres in our country. Patients present with non-specific symptoms and the majority were detected on incidental imaging. We conclude that imaging is likely to play a more important role and further efforts need to be expended on early detection of lung cancer in this increasing cohort without any observable risk factors.

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    P1.06 - Poster Session/ Screening and Early Detection (ID 218)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Screening and Early Detection
    • Presentations: 1
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      P1.06-018 - Can 30-Mortality after Lung Cancer Resection Be Used as an Individual Surgeon Quality Outcome Internationally? National Data from the UK (ID 2866)

      09:30 - 17:00  |  Author(s): M.E. Cufari

      • Abstract
      • Slides

      Background:
      Internationally, one of the most commonly reported quality outcome in surgery for lung cancer is 30 day mortality. However, is difficult to know what constitutes unacceptably high mortality or unacceptable variation between surgeons. In October 2014 national data was released from the Society for Cardiothoracic Surgery (SCTS) in the United Kingdom (UK) on hospital and individual surgeon volume performance for lung cancer resection in the UK. The implicit assumption is benchmarking of the performance. The aim of this study is to report on the impact of individual surgeon volume in relation to each death associated with the an average 30-day mortality rate of 2.2% using national data driven performance control limits (i.e. funnel plots), and determine the applicability on surgeon performance internationally.

      Methods:
      Data released by the SCTS were downloaded, complied and analysed. Each step change for individual mortality was calculated, and alert limits modelled using current UK national standard of the upper 99% binomial confidence limit.

      Results:
      Data from 29 units were published with the annual volume of 125 surgeons for 2012. Data from 6 surgeons were excluded for no lung resections performed. In the remaining 118 surgeons, the mean (SD) annual lung resection volume for cancer was 42 (27). A total of 25% of surgeons performed 18 resections (or less) per year. For 50% of surgeons undertaking 40 resections (or less) each death represents at least 2.5% (0 to 13%) of their annual work load. Using a 99% binomial confidence limit at 50 cases, the upper alert is 16%. Therefore for the majority of surgeons, a mortality rate of 15% which is 7.5 fold higher than average would not trigger the conventional national alert limits.

      Conclusion:
      Based on UK national data, lung cancer resection volumes for individual surgeons are low and for the majority even a single death (which could be due to chance), affects the overall mortality rate much more, carries a disproportionately high weighting and may encourage risk adverse behaviour whilst simultaneously failing to detect 7.5 fold increased mortality rates using conventional national limits. Such data driven limits would also not be applicable on an international level basis unless individual surgeon volume is higher than 100 resections per year, a level that was not achieved by most UK surgeons.

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    P3.06 - Poster Session/ Screening and Early Detection (ID 220)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Screening and Early Detection
    • Presentations: 1
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      P3.06-015 - Is the Development of Primary Lung Adenocarcinoma Simply Due To 'Bad Luck'? (ID 2825)

      09:30 - 17:00  |  Author(s): M.E. Cufari

      • Abstract
      • Slides

      Background:
      Recently, Tomasetti and Vogelstein proposed that the variation in cancer risk among tissue is explained by the number of stem cell division, and this was widely interpreted as “bad luck” due to random mutations arising during DNA replication in normal non-cancerous stem cells. Smoking is widely considered as the main aetiological risk factor for the lung cancer and the aim of our study is to evaluate the hypothesis comparing the differences in proportions of the two main histological subtypes in smokers and never smokers in a patients with early stage primary lung cancer to determine the impact of smoking on the development of squamous and adenocarcinoma.

      Methods:
      Data were retrospectively analysed from a prospectively collated database at our institution over a 7 year period. Histological data were extracted and compared for the two main historical subtypes of squamous and adenocarcinoma (subtyped according to the new IASLC adenocarcinoma classification). Frequencies were compared using Fishers exact or Chi square tests as appropriate to the data.

      Results:
      A total of 2170 patients underwent surgical resection for lung cancer at our institution from March 2008 to November 2014 of which 436 (20%) patients were never smokers. The mean age (SD) was 66 (12) years and 48% were female. The relative proportion of patients with squamous carcinoma was significantly different between smokers 323 (27.0%) and never-smokers 16 (5.7%) with P <0.001 with a risk ratio of 4.70 (95% CI 2.9 to 7.6). However the relative proportions between patients with adenocarcinoma were similar between smokers 578 (48.3%) and never-smokers (54.4%) P=0.06 with a risk ratio of 0.89 (0.79 to 1.00).

      Conclusion:
      Our results suggest that smoking remains an important aetiological risk factor for the development of primary lung squamous cell carcinoma. For adenocarcinoma, the relative proportions between smokers and never-smokers were similar (in fact lower for smokers) supporting Tomasetti and Vogelstein hypothesis of random mutations arising during DNA replication in normal non-cancerous stem cells– or simply put as “bad luck”.

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