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P.Y. Yip



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    P2.06 - Poster Session 2 - Prognostic and Predictive Biomarkers (ID 165)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P2.06-011 - Phosphorylated-Akt expression is a prognostic marker in early stage non-small cell lung cancer (NSCLC) (ID 1151)

      09:30 - 09:30  |  Author(s): P.Y. Yip

      • Abstract

      Background
      The 5-year survival for stage IB non-small cell lung cancer (NSCLC) is only 55%, but the benefit of adjuvant chemotherapy in this setting remains equivocal. Numerous prognostic markers have been examined, but none to date have moved into clinical practice. There is an urgent need to identify novel molecular markers that can select high risk patients, who may potentially benefit from adjuvant chemotherapy.

      Methods
      We identified 471 consecutive patients with stage IB primary NSCLC according to the American Joint Commission on Cancer, (AJCC) 6[th] edition tumour-node-metastasis staging system, who underwent surgical resection between 1990 and 2008. Patients who received neoadjuvant or adjuvant treatments were excluded. Pathology reports were reviewed and pathologic characteristics were extracted. Expression of phosphorylated Akt (pAkt) in both cytoplasmic and nuclear locations was assessed by immunohistochemistry, and clinicopathologic factors were analyzed against 10-year overall survival using Kaplan-Meier and Cox proportional hazards model.

      Results
      455 (96.6%) cancers were adequate for pAkt immunohistochemical analysis. The prevalence of pAkt expression in the cytoplasm and nucleus of the cancers was 60.7% and 43.7% respectively. Patients, whose cancers expressed higher levels of pAkt in the cytoplasm, had a trend towards longer overall survival than those with lower levels of cytoplasmic pAkt (p=0.06). Conversely, patients whose cancers expressed higher levels of pAkt in the nucleus had a poorer prognosis than those with lower levels of nuclear pAkt expression (p=0.02). Combined low cytoplasmic/high nuclear expression of pAkt was an independent predictor of overall survival [HR=2.86 (95% CI:1.35-6.04); p=0.006] when modeled with age [HR= 1.05 (95% CI: 1.03-1.07); p<0.001], extent of operation [HR= 2.11 (95% CI: 1.48-3.01); p<0.001], visceral pleural invasion [HR=1.63 (95% CI: 1.24-2.15); p<0.001], gender, tumour size, histopathologic type and grade (p>0.05).

      Conclusion
      Levels of expression of pAkt in the cytoplasm and nucleus and visceral pleural invasion are independent prognostic factors that can help to select patients with high risk disease, who may potentially benefit from adjuvant chemotherapy.

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    P2.10 - Poster Session 2 - Chemotherapy (ID 207)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P2.10-030 - Eastern Cooperative Oncology Group (ECOG) score: Agreement between non-small-cell lung cancer (NSCLC) patients and their oncologists and clinical implications (ID 1792)

      09:30 - 09:30  |  Author(s): P.Y. Yip

      • Abstract

      Background
      Oncologists use ECOG score to assess patients’ performance status (PS) and guide treatment decisions, but patients and doctors do not necessarily agree on their score. We compared ECOG scores assessed by NSCLC patients and their oncologists to determine if this has implications on treatment and survival prediction.

      Methods
      NSCLC patients who underwent chemotherapy in prospective inter-ethnic difference and nutrition studies at Concord Hospital were included. Patients self-assessed their ECOG score as part of the Patient-Generated Subjective Global Assessment questionnaire prior to chemotherapy. Kappa was used to assess agreement of ECOG score between patients and oncologists. Survival was calculated from date of chemotherapy, using Kaplan Meier method.

      Results
      79 patients (median age 63 years, 86% Stages IIIB/IV, median survival of 15.5 months) were included. ECOG scores differed in 34 (43%) cases (Table).The interrater reliability between patients and their oncologists was Kappa = 0.35 (p <0.001). Figure 1 If patient ECOG scores were used, 11 patients (14%) would be deemed unfit for chemotherapy (ECOG≥3) and 21 patients (27%) would be excluded from clinical trials (ECOG≥2). ECOG status (0 versus >0) irrespective of assessor was predictive of overall survival (18.7 vs. 12.1 months with p=0.023 and 17.4 vs. 11.1 months with p=0.017 for patient and oncologist-assessed ECOG respectively). In patients whose ECOG score was assessed to be 0 by their oncologist (n=39), a worse survival was associated with a poorer patient assessed PS (median survival 16.7 vs. 18.2 months for patient assessed ECOG >0 vs. ECOG=0 respectively; p=0.31).

      Conclusion
      Both physician and patient-assessed ECOG scores are predictive of overall survival. In this study, there was only fair agreement in ECOG assessed by NSCLC patients and their oncologists, with patient scores usually poorer. A number of patients would have excluded themselves from therapeutic interventions including clinical trials based on their ECOG PS rating. Patient-assessed ECOG scores of > 0 may be associated with worse survival despite their oncologist’s more optimistic scoring, a finding which may be incorporated to benefit clinical decision-making.

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    P3.12 - Poster Session 3 - NSCLC Early Stage (ID 206)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P3.12-009 - Patterns of care in patients receiving adjuvant chemotherapy for resected non-small cell lung cancer (NSCLC) in South Western Sydney Local Health District (SWSLHD) (ID 2093)

      09:30 - 09:30  |  Author(s): P.Y. Yip

      • Abstract

      Background
      Randomised controlled trials have shown that adjuvant chemotherapy is the standard of care for patients with resected, stages II and IIIA NSCLC. The benefit in stage IB disease remains inconclusive. There are limited data regarding the patterns of care, benefits and toxicities of adjuvant chemotherapy in the non-clinical trial population. We reviewed patterns of care and survival outcomes in patients with resected NSCLC receiving adjuvant chemotherapy.

      Methods
      We retrospectively reviewed medical records for patients with resected, pathologic stages IB-IIIA NSCLC diagnosed between 1/1/2005 and 31/12/2012 in SWSLHD. Patients were identified using an institutional electronic database. Staging was according to the American Joint Commission on Cancer (AJCC) 6[th] edition tumour-node-metastasis (TNM) system. Information was extracted on baseline patient and tumour characteristics, treatment modalities, chemotherapy delivery, treatment-related toxicities and patient outcomes. Survival analysis was performed using Kaplan-Meier method.

      Results
      We identified 137 patients who underwent surgical resection, 63 (46%) received adjuvant chemotherapy and are presented in this analysis. The main reasons that patients did not receive adjuvant chemotherapy included stage IB disease (32%), advanced age/comorbidities (24%), patient preference (14%), prior neoadjuvant treatment (7%) and non referral (7%). The median age at diagnosis was 64 (range 45 - 77) with 57% male, 81% were ex- or current smokers and 80% had an ECOG performance status of 0 or 1. Adenocarcinoma and squamous cell carcinoma histology accounted for 54% and 27%, respectively. Forty one patients (65%) had lobectomy and 22 (35%) had pneumonectomy. Pathological stage was: 1B 5 patients (7.9%), IIA 11 (17.5%), IIB 13 (20.6%) and IIIA 34 (54%). Adjuvant chemotherapy commenced within 90 days of surgery in 94% with a median time to treatment of 60 days (range 25-110). Adjuvant radiotherapy was given to 18 patients (29%), with 52% of patients with N2 disease receiving radiotherapy. Platinum doublet chemotherapy was administered to 62 patients (98%) and cisplatin/vinorelbine was the most common regimen given to 41 patients (65%). The number of planned treatment cycles was completed by 40 patients (63%), and of these, 11 patients (17%) completed all chemotherapy on schedule without dose modification. Eighteen patients (29%) required hospitalisation during treatment. Febrile neutropaenia occurred in 10 (16%), with an additional 24 (38%) developing non-febrile neutropaenia, thrombocytopenia or anaemia. Other clinically significant non-haematological toxicities included: vomiting (11%); renal impairment (10%); ototoxicity (6%); peripheral neuropathy (16%); fatigue (6%); allergy (2%) or myalgias (3%). There were no toxic deaths. With a median follow-up of 18.6 months (range 3.4 to 96 months), 56% had developed recurrent disease with a median disease-free survival of 18.9 months. The majority (94%) developed recurrent disease within 3 years. The median overall survival was 25.6 months. A total of 34 (54%) had died, including 3 non-cancer related deaths.

      Conclusion
      The utilisation of adjuvant chemotherapy rate is moderate but is consistent with other reports. Our results demonstrated a higher rate of febrile neutropenia and shorter median overall survival than the clinical trial population. Therefore, careful selection of patients to undergo adjuvant chemotherapy is essential.

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    P3.18 - Poster Session 3 - Pathology (ID 177)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Pathology
    • Presentations: 1
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      P3.18-003 - ROS1 Gene Rearrangements in Non-Small Cell Lung Carcinoma - A New Genetic Target that can be Identified by Immunohistochemistry and FISH (ID 1482)

      09:30 - 09:30  |  Author(s): P.Y. Yip

      • Abstract

      Background
      Targeted therapies aimed at specific molecular genetic alterations are revolutionizing cancer treatment, particularly in non-small cell lung cancer (NSCLC). ROS1 is an oncogene that encodes a transmembrane tyrosine kinase receptor that has high homology with the intracellular kinase domain of ALK. Driver mutations involving translocation of the ROS1 gene have recently been identified in NSCLC and show promise as a target for tyrosine kinase inhibitors. In this study we aimed to: (1) Investigate the incidence and clinicopathological features of NSCLCs harbouring ROS1 rearrangements in an Australian population. (2) Investigate the accuracy of immunohistochemistry (IHC) compared to FISH at identifying tumours with ROS1 rearrangements.

      Methods
      We tested for ROS1 translocations using both a FISH breakapart probe (Zytovision and Abbott Molecular) (≥15% cells with split signals or single green 3' signal considered positive for rearrangement), and immunohistochemistry (D4D6 clone, Cell Signaling Technology). Testing was undertaken on both (1) A retrospective cohort of 316 early stage lung adenocarcinomas in tissue microarrays. (2) A prospective cohort of 42 NSCLC, selected on clinical grounds for mutation testing (eg EGFR/KRAS/ALK negative samples and young age or never/light smoker).

      Results
      In the retrospective cohort, only 1 case was positive for ROS1 gene rearrangement by FISH (0.3% incidence). ROS1 IHC identified positive staining in 7 (2.0%) cases, including the FISH+ case. ROS1 IHC had a sensitivity of 100% and specificity of 98% for identifying ROS1 gene rearrangements. In the prospective cohort of 42 cases, 4 cases with ROS1 gene rearrangement were identified by FISH and all 4 cases showed positive ROS1 immunohistochemical staining. Of the total 5 cases with ROS1 gene rearrangement, all occurred in adenocarcinomas from female patients with an age range of 33-81 years (mean 58). Four of the five patients were non-smokers and two were of Asian ethnicity. All 5 cases were negative for ALK rearrangements and in the 4 cases where EGFR status was known, they were all wild type.

      Conclusion
      ROS1 gene rearrangements occur in a very small percentage of lung adenocarcinomas with distinctive clinicopathological features and appear to be mutually exclusive with other driver mutations in the small number of positive cases available for evaluation. Screening with IHC may be a suitable method of reducing the number of cases requiring FISH testing.