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T. Hensing



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    ED 09 - Tissue Is the Issue: Improving Diagnostic Yield in the Age of Minimally Invasive Procedures (ID 9)

    • Event: WCLC 2015
    • Type: Education Session
    • Track: Community Practice
    • Presentations: 1
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      ED09.04 - Prioritization of Tissue Use (ID 1809)

      15:20 - 15:40  |  Author(s): T. Hensing

      • Abstract
      • Presentation

      Abstract:
      The personalized treatment of lung cancer begins with an accurate histologic diagnosis. Lung cancer is a heterogeneous disease and recent advances in understanding the genetic underpinnings of cancer coupled with the development of targeted therapeutics have added to the complexity of the diagnostic evaluation. The previous simple division of lung cancer into small cell and non-small cell histology is no longer adequate, and evaluation of tumors for specific genetic changes and their expression is essential for the precise and accurate diagnoses required for optimal treatment and patient management. In 2011, the International Association for the Study of Lung Cancer (IASLC), the American Thoracic Society (ATS), and the European Respiratory Society (ERS) published a new pathological classification of lung adenocarcinoma.[1] This new system established uniform terminology and diagnostic criteria for both resection specimens and small biopsies. Based on advances in the understanding of lung tumor biology, the correlation between specific tumor histology and outcomes with selected chemotherapy agents, as well as the successful development of novel targeted therapies, this new classification system emphasized the importance of a multidisciplinary approach to the diagnosis of lung cancer in order to best guide management decisions. In the IASLC/ATS/ERS system, several changes to pathological classification of adenocarcinoma were proposed.[1] The term “BAC” (bronchioloalveolar carcinoma) was discontinued and new pathological subtypes were added, including adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma. For patients with invasive adenocarcinoma, the new system proposed comprehensive histological subtyping with classification based on predominant histological pattern (lepidic, acinar, papillary, micropapillary and solid). Mucinous tumors were classified as mucinous AIS, mucinous MIA or invasive mucinous adenocarcinoma based on extent of invasion. In subsequent validation studies, pathological subtyping using the IASLC/ATS/ERS adenocarcinoma classification system has been demonstrated to have both prognostic and predictive significance.[2, 3] Patients with AIS and MIA have close to 100% disease-free survival. In contrast, invasive adenocarcinomas with solid and micropapillary predominant histological subtypes were associated with worse overall survival.[2, 4] Because most patients with lung cancer will be diagnosed with advanced-stage disease, one of the most important distinctions between the 2011 IASLC/ATS/ERS classification system and the previous 2004 World Health Association (WHO) classification is the establishment of diagnostic criteria for small biopsies and cytology. Although the focus was on adenocarcinoma, diagnostic criteria for other histologies were also included with the primary focus on distinguishing between squamous cell carcinoma and adenocarcinoma. A limited diagnostic work up was recommended to preserve as much tissue as possible for molecular testing. In cases where the diagnosis can be established based on light microscopy alone, the WHO classification criteria were maintained and no additional confirmatory testing was recommended. In tumors without definite squamous or adenocarcinoma morphology, limited immunohistochemistry may be used to refine the diagnosis. Most tumors can be classified using a single adenocarcinoma marker (i.e. TTF-1 or mucin) and a single squamous marker (i.e. p40 or p63.[5] The acknowledgement that one needs to “preserve as much tissue as possible” for biomarker testing reflects the changing uncertainty in which biomarkers need to be assessed and what techniques might be available for testing. With the identification and validation of actionable molecular targets that can guide therapy in patients with advanced adenocarcinoma, institutions are encouraged to develop consistent strategies for obtaining and managing tissue samples that are optimized for molecular testing. Because this approach has not been validated for squamous histology, tumors with equivocal morphology or IHC findings should be classified as NSCLC-NOS so as not to exclude patients from histology-specific chemotherapy or molecular testing. In 2013, the College of American Pathologists (CAP), IASLC and Association for Molecular Pathology (AMP) published a molecular testing guideline for selection of lung cancer patients for EGFR and ALK tyrosine kinase inhibitors that included 37 recommendations addressing 5 principal questions, including: (1) When should molecular testing be performed? (2) How should EGFR testing be performed? (3) How should ALK testing be performed? (4) Should other genes be routinely tested in lung adenocarcinoma? And, (5) How should molecular testing be implemented and operationalized?[6, 7] In addition to EGFR and ALK, a number of other molecular alterations have been described that are potentially treatable with targeted agents. Because the data were insufficient to support routine testing of other targets when the CAP/IASLC/AMP guidelines were finalized, the recommendation was to prioritize EGFR and ALK testing over other molecular markers in order to reserve tissue for these analyses.[6] The type and number of molecular alterations being evaluated ultimately determine how a limited specimen should be used. Immununohistochemical (IHC) and Fluorescent In Situ Hybridization (FISH) are the standard approaches for the detection of protein expression and chromosomal rearrangements and amplifications. Specific single nucleotide polymorphisms (SNPs) that are recognized mutations influencing response to specific therapies demand nucleic acid based tests utilizing a PCR based approach or, in the extreme, DNA sequencing. Most of these assays are typically developed as singleton tests for one specific SNP. As the number of necessary biomarkers increases, efficiency demands multiplexing these singleton assays or adopting a different technology, e.g. Next Gen Sequencing (NGS).[8-10] However, the timeliness for reporting results vary depending on the platform and the number of genes. It needs to be understood that none of these technologies can detect all of the types of genomic alterations of interest and that all of these methodologies must remain in the armamentarium available for proper specimen evaluation. With this in mind, efficient use of limited tissue demands clear communication between oncologists, surgeons, interventional radiologists and pathologists with regard what is needed for patient care and an understanding of available resources, either in house or through an appropriate reference laboratory. A further complexity is the timeliness in obtaining a result. While good practice suggests establishment of institutional protocols, individual patient needs ultimately dictate how best to proceed, emphasizing the importance of good interdisciplinary communication References: 1. Travis, W.D., et al., International association for the study of lung cancer/american thoracic society/european respiratory society international multidisciplinary classification of lung adenocarcinoma. J Thorac Oncol, 2011. 6(2): p. 244-85. 2. Hung, J.J., et al., Prognostic value of the new International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society lung adenocarcinoma classification on death and recurrence in completely resected stage I lung adenocarcinoma. Ann Surg, 2013. 258(6): p. 1079-86. 3. Song, Z., et al., Prognostic value of the IASLC/ATS/ERS classification in stage I lung adenocarcinoma patients--based on a hospital study in China. Eur J Surg Oncol, 2013. 39(11): p. 1262-8. 4. Gu, J., et al., Prognostic significance of the IASLC/ATS/ERS classification in Chinese patients-A single institution retrospective study of 292 lung adenocarcinoma. J Surg Oncol, 2013. 107(5): p. 474-80. 5. Travis, W.D., et al., Diagnosis of lung cancer in small biopsies and cytology: implications of the 2011 International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification. Arch Pathol Lab Med, 2013. 137(5): p. 668-84. 6. Lindeman, N.I., et al., Molecular testing guideline for selection of lung cancer patients for EGFR and ALK tyrosine kinase inhibitors: guideline from the College of American Pathologists, International Association for the Study of Lung Cancer, and Association for Molecular Pathology. J Thorac Oncol, 2013. 8(7): p. 823-59. 7. Leighl, N.B., et al., Molecular testing for selection of patients with lung cancer for epidermal growth factor receptor and anaplastic lymphoma kinase tyrosine kinase inhibitors: American Society of Clinical Oncology endorsement of the College of American Pathologists/International Association for the study of lung cancer/association for molecular pathology guideline. J Clin Oncol, 2014. 32(32): p. 3673-9. 8. Rekhtman, N., et al., Suitability of thoracic cytology for new therapeutic paradigms in non-small cell lung carcinoma: high accuracy of tumor subtyping and feasibility of EGFR and KRAS molecular testing. J Thorac Oncol, 2011. 6(3): p. 451-8. 9. Sholl, L.M., et al., Multi-institutional Oncogenic Driver Mutation Analysis in Lung Adenocarcinoma: The Lung Cancer Mutation Consortium Experience. J Thorac Oncol, 2015. 10(5): p. 768-77. 10. Gailey, M.P., et al., Multiplatform comparison of molecular oncology tests performed on cytology specimens and formalin-fixed, paraffin-embedded tissue. Cancer Cytopathol, 2015. 123(1): p. 30-9.

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    P1.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 206)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Treatment of Advanced Diseases - NSCLC
    • Presentations: 1
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      P1.01-061 - The Chicago Thoracic Oncology Database Consortium: A Multi-Site Database Initiative (ID 946)

      09:30 - 09:30  |  Author(s): T. Hensing

      • Abstract
      • Slides

      Background:
      An increasing amount of clinical data is available to biomedical researchers, but specifically designed databases and informatics infrastructures are needed to handle this data effectively. Multiple research groups should be able to pool and share this data in an efficient manner. The Chicago Thoracic Oncology Database Consortium (CTODC) was created to standardize data collection and facilitate the pooling and sharing of data at institutions throughout Chicago and across the world.

      Methods:
      The Salgia Laboratory has implemented the Thoracic Oncology Program Database Project (TOPDP) Microsoft Access, the TORP Velos, and the TORP REDCap databases for translational research efforts. Standard operating procedures (SOPs) were created that document the construction and proper utilization of these databases. These SOPs have been made available freely to other institutions that have implemented their own databases patterned on these SOPs. In order to evaluate the effectiveness of this consortium, we have performed an investigation examining patients receiving erlotinib at three institutions belonging to the CTODC: The University of Chicago Medical Center, Ingalls Health System, and NorthShore University Health System.

      Results:
      A cohort of 373 lung cancer patients who are taking erlotinib was identified by querying data from all three institutions of the consortium. The patients’ demographic and clinical data were compiled. In addition, the EGFR statuses of patients were analyzed, showing that out of the 70 patients that were tested, 55 had mutations while 15 did not have any mutations. The overall survival and duration of treatment were calculated from the data that was provided. It was shown that patients with an EGFR mutation had longer duration of erlotinib treatment and longer overall survival compared to patients who received erlotinib and were EGFR wild type.

      Conclusion:
      The investigation described herein demonstrates the successful data collection from multiple institutions in the context of a collaborative effort. However, the investigation identified many challenges in this type of collaboration, such as difficulty of transferring data between institutions and potential duplication of patient data. Overall, these issues do not lessen the findings of the investigation or the effectiveness of the CTODC. With greater cooperation and communication between institutions of the consortium, these issues can be readily resolved. The data presented here can be utilized as the basis for further collaborative efforts and/or development of a larger, more streamlined collection of databases within the consortium.

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