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W..D. Wallace
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MINI 25 - Trials, Radiation and Other (ID 142)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Thymoma, Mesothelioma and Other Thoracic Malignancies
- Presentations: 1
- Moderators:J.M. Clavero, R. Hassan
- Coordinates: 9/08/2015, 16:45 - 18:15, 702+704+706
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MINI25.12 - Hospital Resource Utilization and Outcomes of Pleurectomy Compared to Extrapleural Pneumonectomy for Mesothelioma (ID 2539)
17:50 - 17:55 | Author(s): W..D. Wallace
- Abstract
Background:
Although extrapleural pneumonectomy (EPP) and pleurectomy/decortication (P/D) provide similar survival in malignant pleural mesothelioma (MPM), we sought to compare the two procedures in terms of another important outcome" hospital resource utilization (RU).
Methods:
With IRB approval, we retrospectively reviewed our prospective database to determine RU (ICU and hospital stay, mechanical ventilation, and central line use, etc) and Kaplan-Meier median survival (MS) for patient undergoing P/D. Our results are compared with similar findings for EPP reported in the literature.
Results:
We identified 121 pts on an "intent to treat" basis from 1997-2011. 94 (77.7%) were male. Mean age was 65.9 yrs (range 27-84). Comorbidities included hypertension 45.5%, coronary artery disease 11.6%, diabetes 10.7%, and vascular disease 6.2%. Mean surgical time was 7 hrs 57 mins (range 3 hrs 15 min–14 hrs 21 min). R1 resection was achieved in 116 (95.9%). Microscopic "margins" were assessed in 63 with 40 (63.5%) positive. Pathologic T- and N-staging is shown in Table 1. Morbidity was mostly limited to air leaks >10 days 41 (33.9%) and atrial arrhythmias 38 (31.4%). Three patients (2.5%) died. Relevant RU data included: intraoperative CVP lines 3 (2.5%), OR extubation 113 (93.4%), no ICU stay 99 (81.7%), and mean hospital stay 10 (range 5-103) days. RU data with P/D + RTx is compared to EPP as reported by others (figure 1). MS was 13.8 mos for all patients and 17.8 mos for epithelioid histology, which was better than biphasic (10.3 mos) and sarcomatoid (2.1 mos) subtypes (p<0.01). MS for 85/121 patients (70.2%) who completed P/D + RTx was 19.7 mos. MS for similar groups of EPP patients is reportedly 16.8-19 mos (eg, Thorac Cardiovasc Surg 1999;117(1):54-65 and J Clin Oncol 2009;27(18):3007-13).Conclusions: P/D +RTx provide essentially the same outcomes as EPP with less use of hospital resources
Figure 1T Stage N Stage 0 0 57(47.1%) 1 0 3(2.5%) 2 24(19.8%) 58(47.9%) 3 70(57.9%) 0 4 27(22.3%) -
Conclusion:
P/D provides essentially the same outcomes as EPP with less use of hospital resources.
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ORAL 05 - Surgery (ID 97)
- Event: WCLC 2015
- Type: Oral Session
- Track: Treatment of Locoregional Disease – NSCLC
- Presentations: 1
- Moderators:P. Van Schil, F.(. Kong
- Coordinates: 9/07/2015, 10:45 - 12:15, 201+203
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ORAL05.03 - Transcervical Mediastinal and Hilar Lymphadenectomy (TCML) Provides Accurate Pre-Treatment Cancer Staging and Facilitates Resection (ID 561)
11:27 - 11:38 | Author(s): W..D. Wallace
- Abstract
Background:
We sought to show that TransCervical Mediastinal and hilar Lymphadenectomy (TCML), using standard mediastinoscopy equipment, reliably accesses both mediastinal and hilar lymph node stations, provides accurate pre-treatment cancer staging, and facilitates Minimally-Invasive Cancer Resection (MICR) via removal of nodes traditionally dissected during definitive cancer resection.
Methods:
We reviewed our prospective databases for patients who had TCML - complete removal of lymph node tissue (not sampling) using a standard mediastinoscope +/- video-assistance. Pathological findings from TCML and definitive cancer resections were correlated. TCML's impact on cancer resection was assessed.
Results:
From 2004-2011, 372 patients, mean age 68.4 (28-93) years, 239 (64%) males and 133 (36%) females, had TCML. Cancer diagnoses included lung 306 (82.3%) and other 37 (17.8%). Median surgical time was 93 mins (supervised residents). There were no intra-operative complications or deaths and only 9 (2.4%) postoperative complications. The mean number of individual lymph nodes removed was 31.2/patient (range 7-78). The total and mean numbers of nodal stations removed/patient are shown the Figure (mean = 7), and specific lymph node stations removed are shown in the Table. Although hilar nodes were removed in <43%, in specific circumstances, such as RUL tumors with neg. mediastinal nodes, hilar nodes were removed in 20/29 (69%) of cases. MICR immediately after TCML usually was technically easier and faster because of the hilar dissection When resections were delayed 3-7 days, TCML was less technically beneficial because of inflammation and scarring, and delays >1 week resulted in significant detrimental effects on resection. Complete removal of all nodal tissue was confirmed during definitive cancer resection in >98% thereby providing accurate pre-resection cancer staging. Figure 1Data represents the percentage of the 372 TCML cases with the specified lymph node stations surgically addressed
Right (%) Left (%) Midline (%) Level 1 4.3 0.54 Level 2 78.23 38.17 Level 4 97.58 94.62 Level 10 43.01 24.19 Level 11 28.49 9.41 Level 12 (upper lobe) 10.75 3.23 Level 12 (lower lobe) 0.27 0.54 Level 12 (middle lobe) 1.35 N/A Level 8 2.69 3.49 Level 9 0.00 0.27 Level 5 2.51 Level 6 4.03 Level 3 (anterior) 5.38 Level 3 (posterior) 1.62 Level 7 95.43
Conclusion:
TCML is safe, accurate and feasible without elaborate instrumentation. TCML is capable of reliably accessing not only mediastinal but also hilar nodal stations and facilitates MICR if performed within 7 days of TCML.
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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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P3.04-063 - The Mutational Landscape of Pulmonary Premalignancy in the Context of Lung Adenocarcinoma (ID 1614)
09:30 - 09:30 | Author(s): W..D. Wallace
- Abstract
Background:
While genomic alterations in lung cancer are being actively investigated, the early mutational events that occur within the pulmonary field of cancerization that subsequently drive early carcinogenesis are poorly understood. As a result, the clinical importance of premalignant lesions remains enigmatic. Epithelial cells in the field of lung injury can give rise to distinct premalignant lesions that may bear unique genetic aberrations. A subset of these lesions may progress to invasive cancer, however the mutational landscape that may predict progression has not been determined. In the present study we performed whole exome DNA sequencing to measure the incidence of somatic DNA alterations in matched sets of primary tumor, premalignant lesions and adjacent normal lung tissues.
Methods:
FFPE tissue blocks from 41 patients were obtained from the UCLA Lung Cancer SPORE Tissue Repository. The following regions were dissected from distal airways utilizing Laser Capture Microdissection: a) normal airway epithelial cells (1-3 regions), b) premalignant atypical adenomatous hyperplasia (AAH, 2-4 regions), c) adenocarcinoma in situ (AIS, 1-3 regions) and, d) adenocarcinoma (ADC, 1-3 regions). DNA was extracted and sequencing libraries were constructed followed by exome capture. Sequencing was performed on an Illumina HiSeq2000 with a mean coverage of ~50x per base.
Results:
Data analysis included analyses for germline and somatic variants, loss of heterozygosity and copy number alternations. Within each case, position-specific missense and nonsense mutations were compared. Different cases were compared for the mutations at a gene-specific level. Mutations found only in AAH lesions were defined as premalignant, in ADC as malignant, and in both AAH and ADC as progression-associated mutations. The analysis demonstrated that AAH lesions from the same patient often have different mutational profiles. We identified novel recurring progression-associated mutations in 33 genes, most of which have not been previously described as key drivers for lung cancer. Interestingly, recurring mutations were found in genes involved in calcium signaling and extracellular matrix/receptor interaction. The data was compared to the TCGA and COSMIC databases. Among affected proteins, only 3% overlapped with the COSMIC and approximately 6% with the TCGA database. Interestingly, all of the mutations overlapping with the COSMIC, were found to be common mutations in AAH. Furthermore, pathways affected by the mutated genes were identified utilizing Gene Ontology and pathways from the KEGG, Biocarta or Reactome databases. The observation that few genes mutated in both AAH and ADC are known as key drivers, indicates that: a) progression-associated mutations might facilitate malignant transformation by mutated key driver(s), or b) a combination of two or more progression-associated mutations that are not oncogenic alone, might drive malignant transformation. These hypotheses will be further tested by mapping progression- and malignant-associated genes in the context of pathways.
Conclusion:
Our data indicate that premalignant lesions from the same patient may have different mutational profiles. This inter-lesion heterogeneity suggests that a progression-associated mutational landscape could be defined in longitudinal studies of pulmonary premalignancy. These results could help identify targets for the development of targeted chemopreventive strategies for lung cancer. Supported by EDRN (U01CA152751-AS).