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D.B. Allison



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    P2.06 - Poster Session/ Screening and Early Detection (ID 219)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Screening and Early Detection
    • Presentations: 1
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      P2.06-020 - Comparison of Cytological Diagnosis Between Solitary and Semi-Solitary Lung Nodules in Biopsy Samples: Experience from a Single Academic Center (ID 769)

      09:30 - 09:30  |  Author(s): D.B. Allison

      • Abstract

      Background:
      The recent large scale National Lung Cancer Screening Trial in the United States (NLST) demonstrated an increased detection of stage I lung cancers. This approach was associated with a 20% reduction of lung cancer-related deaths in the screening population. However, the current clinical guideline for the management of lung nodule is primarily based on studies of non-calcified solitary pulmonary nodules (SPN). Although several recent studies have addressed the issue of the management of semi-solitary and/or partially calcified lung nodules, the evidence-based study is still necessary. Clinically, the diagnosis of small pulmonary nodules involves the combination of radiological surveillance and the morphological examination of pulmonary cells, such as bronchoscopic sampling of the lesion, including bronchial brushing and/or transbronchial fine needle aspiration biopsy (TBNA) with or without ultrasound guidance. In this study, we correlated cytomorphological diagnoses of lung nodules with radiological characteristics, and compared them with findings of mediastinal lymph nodes (LN) fine needle aspiration (FNA) biopsy.

      Methods:
      A total of 300 lung and mediastinal LN cases over a one-year period were identified by a computer search, including 117 lung and 183 lymph nodes biopsies. All cases were divided into three categories: solitary, semi-solitary and partially calcified nodules/lesions according to radiographic image. The cytological diagnoses of all cases were correlated with radiographic findings.

      Results:
      In lung biopsies, the average sizes of the solitary, semi-solitary and calcified lesions were 1.952+/-2.225, 1.333+/-1.827, and 1.152+/-1.984 cm, whereas, in lymph nodes the average sizes of the solitary, semi-solitary and calcified lesions were 1.696+/-2.225, 0.909+/-1.041, and 2.788+/-3.371 cm. The cytological diagnosis was summarized in the table.

      Lesions Lung (n=117) Lymph node (n=183)
      Malignant Benign Suspicious Malignant Benign Suspicious
      Solitary (lung n=88) (LN n=156) 58 (65.9%) 23 (26.1%) 7 (8.0%) 136 (87.2%) 20 (12.8%) 0
      Semi-solitary (Lung n=23) (LN n=23) 8 (34.8%) 12 (52.2%) 3 (13.4%) 21 (91.3%) 2 (8.7%) 0
      Calcified (Lung n=6) (LN n=4) 2 (33.3%) 3 (50%) 1 (16.7%) 4 (100%) 0 0
      Total 68 (58.1%) 38 (32.5%) 11 (9.4%) 161 (88%) 22 (12%) 0


      Conclusion:
      In suspicious solitary and semi-solitary lung nodules, the malignancy was diagnosed as 65.9% and 34.8%, respectively. In suspicious solitary and semi-solitary lymph nodes, the malignancy was diagnosed as 87.2% and 91.3%, respectively. In lung lesions with partial calcifications (we only had very limited number of cases), approximately 50% were malignant lesions. In addition to radiological evaluation, the cytomorphological evaluation of semi-solitary and partially calcified nodules is still crucial for the accurate diagnosis and the appropriate clinical management of lung nodules patients.

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    P3.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 235)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Biology, Pathology, and Molecular Testing
    • Presentations: 1
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      P3.04-050 - Detection of PIK3CA Mutations, including a Novel Mutation of V344G in Exon 4, in Metastatic NSCLC: A Retrospective Study of 139 FNA Cases (ID 957)

      09:30 - 09:30  |  Author(s): D.B. Allison

      • Abstract
      • Slides

      Background:
      Several molecular alterations of PIK3CA (phosphatidylinositol-4,5-biphosphate 3-kinases, catalytic subunit alpha) signaling pathways have been detected in primary non-small cell lung carcinoma (NSCLC). These include genomic amplifications of the regulatory subunit p85 and the catalytic subunit p110 alpha, as well as mutations of the helical binding domain on exon 9 and the catalytic subunit on exon 20. A mutation in the PIK3CA gene is a much rarer event than amplification in NSCLCs (approximately 2% in primary NSCLCs). The clinical significance of PIK3CA mutations in carcinoma is still not fully understood and is controversial. For example, some have suggested that PIK3CA mutations are associated with a favorable prognosis in breast cancer, while others have found PIK3CA mutations to be associated with a poor prognosis in primary lung cancers. Additionally, PIK3CA alterations have been associated with EGFR, KRAS and AKT mutations in primary NSCLC. In this study, we have collected FNA specimens of metastatic NSCLCs, investigated PIK3CA mutations, and correlated the findings with other molecular results.

      Methods:
      We identified 139 fine needle aspiration (FNA) cases of metastatic NSCLC with targeted next-generation sequencing (NGS) analyses of AKT, BRAF, EGFR, ERBB2, KRAS, NRAS, and PIK3CA genes, as well as testing for ALK gene rearrangements by fluorescence in situ hybridization (FISH) at the Johns Hopkins Medical Institute.

      Results:

      Age Sex Location Diagnosis PIK3CA Mutation (exon #) EGFR Mutation BRAF Mutation KRAS Mutation
      63 F LN ADC R88Q (1) (-) V600E (-)
      69 M LN ADC V344G(4) E709A (-) (-)
      G719C
      53 F PL ADC V344G(4) T790M (-) (-)
      E746_A750del
      68 M LN NSCLC E542K(9) (-) (-) (-)
      58 M PL ADC E542K (9) T790M (-) (-)
      L747_A750delinsP
      S768_V769delinsIL (S768I + V769L)
      55 F Pelvic Bone SqCC E545K(9) (-) (-) (-)
      74 F LN ADC P539R(9) (-) (-) G12C
      60 M PR ADC H1047R(20) T790M (-) (-)
      L858R
      K860I
      LN: Lymph node; PL: Pleural fluid; PR Peritoneal fluid. (-): not detected.

      Conclusion:
      PIK3CA mutation was detected in 5.8% of metastatic NSCLCs. The majority of the mutations were located on exon 9 or exon 20; however, a rare mutation in exon 1 was seen in one case. Further, a novel mutation, to our knowledge, for NSCLC was detected (V344G) in exon 4 in two cases. Among PIK3CA mutations, 50.0%, 12.5%, and 12% were associated with EGFR, BRAF, and KRAS mutations, respectively. In contrast to primary NSCLC, we did not find any metastatic cases to contain both PIK3CA and AKT mutations. The unique role of PIK3CA mutation in metastatic NSCLC and its clinical implications need to be further investigated.

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