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M. Weyant
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ED 06 - Treatment of Elderly and High Risk Patients with Localized NSCLC (ID 6)
- Event: WCLC 2015
- Type: Education Session
- Track: Treatment of Localized Disease - NSCLC
- Presentations: 1
- Moderators:A. Ardizzoni
- Coordinates: 9/08/2015, 14:15 - 15:45, 702+704+706
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ED06.03 - Surgery (ID 1796)
15:00 - 15:20 | Author(s): M. Weyant
- Abstract
- Presentation
Abstract:
It is difficult to define what an elderly or truly “high risk” patient is in regards to offering surgical treatment of lung cancer. The World Health organization defines an elderly patient as being over age 65 although most practitioners of thoracic surgery would likely define an elderly patient as someone over age 70 (1) . Likewise the definition of a truly high-risk patient is difficult to determine. These patients are often described as having significant cardiopulmonary or other organ dysfunction that could be potentially worsened by the surgical event. In developed countries the average population age is increasing and the incidence of lung cancer is also increasing in elderly patients. Combined with the natural decline in lung and cardiac function these data suggests that there will likely be a steady and significant increase in elderly and high-risk patients who present for consideration of resection for localized lung cancer. Clinical data in the elderly and high-risk patients is hard to come by, as many of these patients are not represented in clinical trials despite the high proportion of these patients in the lung cancer population. The data that is available is often retrospective in nature but it suggests that treatment decisions in these patient groups should not solely be based on chronological age but should take into account the patient’s life expectancy, quality of life desires, presence of comorbidities, and estimated risks and benefits of the procedure (2). Several studies have demonstrated the feasibility of surgically treating lung cancer in elderly patients including octogenarians. Likewise several studies evaluating patients with compromised lung function and other comorbidities have suggested that surgery is feasible in these patients (3,4). What is not clear is what the true limits of age and underlying organ dysfunction is that represent absolute contraindications to surgery. It is likely that improvements in anesthesia and surgical care have allowed older and more high-risk patients to be operated on safely. The use of video assisted thoracoscopy has greatly enhanced our ability to perform surgical resections on these elderly and high-risk patients. The gold standard operation of lobectomy for these patients can potentially be modified in high risk and elderly patients. Several retrospective studies suggest that in the elderly a lesser resection can be equivalent or superior to lobectomy in survival and perioperative morbidity (5). In addition the use of pneumonectomy in these patients should be avoided as the morbidity and mortality is increased significantly (6). It is clear that treatment with stereotactic radiotherapy will play an emerging role in the therapy if these patients. Long-term follow up is needed to truly understand the utility of radiotherapy in high risk and elderly patients. References 1) World Health Organization. Health statistics and health information systems. Available from URL http://www.who.int/healthinfo/survey/ageingdefnolder/en/index.html. 2) Pallis AG, Gridelli C, Wedding U, Faivre-Finn C, Veronesi G, Jaklitsch M, Luciani A, O'Brien M. Management of elderly patients with NSCLC; updated expert's opinion paper: EORTC Elderly Task Force, Lung Cancer Group and International Society for Geriatric Oncology. Ann Oncol. 2014 Jul;25(7):1270-83. 3) Rivera C, Dahan M, Bernard A et al. Surgical treatment of lung cancer in the octogenarians: results of a nationwide audit. Eur J Cardiothorac Surg 2011; 39: 981–986. 4) Zhang R, Ferguson MK. Video-Assisted versus Open Lobectomy in Patients with Compromised Lung Function: A Literature Review and Meta-Analysis. PLoS One. 2015 Jul 6;10(7) 5) Cheng YD, Duan CJ, Dong S et al. Clinical controlled comparison between lobectomy and segmental resection for patients over 70 years of age with clinical stage I non-small cell lung cancer. Eur J Surg Oncol 2012; 38: 1149–1155. 6) Zuin A, Marulli G, Breda C et al. Pneumonectomy for lung cancer over the age of 75 years: is it worthwhile? Interact Cardiovasc Thorac Surg 2010; 10: 931–935.
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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
- Moderators:D. Jablons, B. Stiles
- Coordinates: 9/08/2015, 16:45 - 18:15, 605+607
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MINI19.05 - Discussant for MINI19.01, MINI19.02, MINI19.03, MINI19.04 (ID 3548)
17:05 - 17:15 | Author(s): M. Weyant
- Abstract
- Presentation
Abstract not provided
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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
- Moderators:
- Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P3.04-052 - Next Generation Exome Sequencing of Archival Lung Cancer Resection Specimens (ID 2159)
09:30 - 09:30 | Author(s): M. Weyant
- Abstract
Background:
Genetic testing of non-small cell lung cancer has grown rapidly in recent years to accommodate expansion of the number of agents with molecular targets. Whole exome sequencing (WES) has been proposed as a method to comprehensively assess tumor mutation status that could replace current piecemeal approaches to predictive testing. The feasibility of WES for formalin fixed paraffin embedded (FFPE) clinical samples has recently been documented. However, several issues remain to be resolved before this platform can be adopted for routine clinical use. The purpose of the present study is to evaluate tissue coring as a method for obtaining DNA from FFPE tumor tissue, to assess the gene coverage of libraries prepared from FFPE, to determine how best to identify specific validated treatment targets, and to determine mutation load in clinical samples.
Methods:
We extracted DNA from 0.6 mm tissue cores selected both from tumor rich regions of paraffin blocks and normal lung tissue. DNA quality was assessed by Bioanalyzer and Qbit testing. A sequencing library was prepared using the Agilent Sure Select XT5 (v5) library kit. DNA was sequenced using an Illumina Hiseq 2500 ultrahigh throughput sequencing system. We used two flow cells for each of 4 samples to obtain a high level of coverage and to determine the effect of reducing coverage on mutation detection by computational methods. We used the DNA from non-tumoral regions to identify genomic polymorphisms and to then compile lists of mutations that were suspected of have a deleterious effect on the host. As a control, we tested DNA from each tumor by a clinically validated multiplexed panel (Illumina True Site panel). We compared our sequencing results with the TCGA database for the respective tumors.
Results:
DNA yield was 13 and 17 micrograms for the SCC and adenocarcinoma respectively. After shearing to 200 base pairs and library preparation, excellent quality DNA was obtained for sequencing. All of the mutations detected by Miseq analysis were detected by WES. Several mutations identified by WES have not been documented in TCGA. The mutations of the two tumors are sumarized below, including mutation load.WES Mutations SCC Adenocarcinoma Nonsynonomous SNV 247 51 Stopgain SNV 16 1 Fs deletion 10 1 Non-fs substitution 9 7 Fs insertion 2 2 Non-fs deletion 1 3 Non-fs insertion 1 0 Stoploss SNV 1 0 Splice region abnormality 9 0 Not present in TCGA 37 7 Present in TCGA 265 59 Mutations detected by Miseq TP53 (p.G245R) EGFR exon19 del CTNNB1 (p.S45C) Total (Mutation Load) 302 66
Conclusion:
This study confirms that WES is feasible on FFPE tissue and that the two tumors sequenced fall into the two categories, high and low mutation loads. The mutations identified include several that have not previously been reported. All mutations identified by high coverage clinical platforms were also detected by WES. WES may be suitbable for clinical application.
