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C. Kennedy



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    P3.06 - Poster Session 3 - Prognostic and Predictive Biomarkers (ID 178)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P3.06-017 - Distinctive Insulin-Like Growth Factor 1 gene copy number and protein expression in non-small cell lung cancer (ID 1753)

      09:30 - 09:30  |  Author(s): C. Kennedy

      • Abstract

      Background
      The insulin-like growth factor (IGF) pathway is involved in the development and progression of many tumours and there is growing preclinical evidence that blockade of this pathway has anti-tumour effects in NSCLC. IGF receptors (IGFR) are another potential target for targeted treatment of NSCLC and a number of agents are already undergoing clinical trial. Biomarkers are needed to select patients most likely to derive clinical benefit from these agents. The downstream pathway components of IGF1R and MET activation include PI3K and AKT, which are other potential biomarkers currently being investigated in this patient cohort. IGF1R has also been implicated in acquired resistance to EGFR-TKI treatments. Only a few small retrospective studies have investigated the prognostic role of IGF1R in NSCLC and the relationship with EGFR mutations is not known.

      Methods
      IGF1R status was evaluated by chromogenic silver in situ hybridization (ISH) and immunohistochemistry (IHC) in tissue microarray sections from a retrospective cohort of 264 surgically resected NSCLCs and results were compared to clinicopathological features and patient survival. Patients were classified as IGF1R gene amplification (either presence of tight gene clusters, IGF1R to CEN15 ratio ≥ 2, or ≥ 15 copies of IGF1R per cell in ≥ 10% of analysed cells); high polysomy (≥ 4 copies of IGF1R in ≥ 40% of tumour cells); low copy number (< 4 copies of IGF1R in < 40% of cells). Patients were also grouped as IGF1R-positve (amplification or high polysomy) or IGF1R-negative (low copy number).

      Results
      High IGF1R gene copy number was identified in 77 cases (29.2%) in which there were 32 amplified IGF1R cases (12.1%) and 45 high-polysomy IGF1R cases (17%). Increased copy number of IGF1R was more common in squamous cell carcinomas (SCC) compared to large cell carcinomas (LCC) or adenocarcinomas (ADC) (p<0.05). There was no correlation between IGF1R gene copy number status and other clinicopathological features including patient age, gender, smoking status, tumour size, vessel, perineural or lymphatic invasion, grade or stage. IGF1R copy number alteration in primary tumours was highly correlated with IGF1R copy number status in metastatic tumours (p<0.01). High IGF1R protein expression was observed in 61/259 (23.6%) primary tumours and 14/215 (6.5%) normal adjacent bronchial mucosae. High expression of IGF1R protein was significantly associated with SCC in comparison with non-SCC primary tumours, as well as with lymphatic and vessel invasion. There was a moderate correlation between IGF1R copy number status (positive versus negative) and IGF1R protein expression (high versus low) (Cramer’s V=0.3, p-value <0.001). Both IGF1R copy number status and protein expression were not associated with patient overall survival in univariate analyses (p>0.05).

      Conclusion
      High IGF1R gene copy number and its protein expression are frequent in NSCLC, particularly in SCC. However, alterations of IGF1R are not associated with patient prognosis. IGF1R gene copy number can readily be assessed in formalin fixed paraffin embedded tissue and warrants further investigation as a potential biomarker of targeted therapy in NSCLC.

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    P3.07 - Poster Session 3 - Surgery (ID 193)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Surgery
    • Presentations: 1
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      P3.07-040 - Temporal trends in surgical outcomes for early stage non-small cell lung cancer (ID 2958)

      09:30 - 09:30  |  Author(s): C. Kennedy

      • Abstract

      Background
      There has been little investigation of temporal trends in outcomes following resection of early non-small cell lung cancer. Analyses are easily confounded by changes in patient characteristics and variations in background mortality when assessing all-cause survival. This study aimed to evaluate changes in patient characteristics, tumour factors and survival over time.There has been little investigation of temporal trends in outcomes following resection of early non-small cell lung cancer. Analyses are easily confounded by changes in patient characteristics and variations in background mortality when assessing all-cause survival. This study aimed to evaluate changes in patient characteristics, tumour factors and survival over time.

      Methods
      A retrospective analysis of 2816 consecutive pathological stage 1A to 3A patients, treated by surgical resection between 1984 and 2007 was performed. Patients were divided into four 6-year eras by date of surgery. Relative survival probabilities were estimated by era and TNM stage. Expected survival was calculated from national age, sex and period specific mortality rates. Multivariable regression using a generalised linear model with Poisson error was used to estimate the excess hazard of death in each era, using the 1984-1989 cohort as the baseline, controlling for age, sex, extent of resection, margin status, tumour stage and cell type.

      Results
      In later eras, patients were older, had a greater proportion of adenocarcinomas and stage 1A tumours. Relative 5-year survival rates for 1984-1989, 1990-1995, 1996-2001 and 2002-2007 were 45.4, 49.6, 48.5 and 57.9% respectively. There was a significant improvement in 5-year relative survival in the 2002-2007 cohort (Excess hazard ratio 0.62, p<0.001). Age ≥75, increasing TNM stage, positive margins and mixed cell type were also significant prognostic factors. The increased survival demonstrated in the most recent era can be attributed primarily to survival gains in stage IIa/b and stage 3a (Figure). Figure 1

      Conclusion
      Temporal trends in patient characteristics in this series mirror recent epidemiological data for non-small cell lung cancer. After controlling for known confounders and background mortality variation, improved survival was demonstrated for more recent patients. Advances in clinical staging and adjuvant therapy may explain these findings.