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R.B. Cameron
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MINI 20 - Surgery (ID 137)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Treatment of Locoregional Disease – NSCLC
- Presentations: 1
- Moderators:G. Veronesi, R. Flores
- Coordinates: 9/08/2015, 16:45 - 18:15, 201+203
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MINI20.07 - Extended Cervical Mediastinoscopy (ECM) for Biopsy of AortoPulmonary Window (APW) Lymph Nodes and an APW Index (APWI) Useful in Patient Selection (ID 565)
17:20 - 17:25 | Author(s): R.B. Cameron
- Abstract
Background:
Biopsy of APW (levels 5/6) lymph nodes can be important for lung cancer staging, but the APW is not accessible by routine mediastinoscopy or EBUS. Although some consider ECM potentially dangerous, we reviewed our ECM experience to determine safety and accuracy and to define/validate parameters for patient selection.
Methods:
With IRB approval we reviewed two institutions' databases for patients undergoing ECM between 3/1/97 and 12/31/11. Physical parameters (PP) that were thought to impact on the difficulty and safety of ECM, ie., clavicular head (CH), thoracic inlet (TI), and anterior mediastinal (AM) dimensions, were measured using 55 CT scans available from the first 100 pts.
Results:
Of 190 patients, 128 (67.3%) were male and ages ranged 28-91 yrs. Indication for surgery was either cancer (>95% with lung cancer >80%) or adenopathy (<5%). All procedures were performed by a single surgeon during routine mediastinoscopy. There were no intraoperative complications and blood loss was <25 cc in all cases. Morbidity occurred in 15 (7.9%) with 1 (0.55%) major complication and no mortality. A pathologic diagnosis was obtained in 189 (99.5%). Postop pain was easily controlled with bupivicaine. PP were compared to those in an additional 12 control patients with failed procedures (Table). Although each PP alone was not useful, the APWI (TI X AM product) did predict degree of difficulty (p=0.015) and divided patients into 3 groups predictive of the degree of difficulty: Straightforward (APWI>17), Intermediate (APWI=6-17), and Prohibitive (APWI<6) (Figure). The APWI was then prospectively validated with excellent accuracy in the next 90 patients. The APWI can be helpful in the selection of patients for thoracic surgeons, particularly those learning ECM. A short video demonstrating the technique of ECM will be presented.Table: Physical Parameter Measurements (values were obtained from CT scans available on 55/100 initial patients comparing with a separate group of 12 patients with unsuccessful ECM
Figure 1Parameter Successful ECM (cms) UnSuccessful ECM (cms) Clavicular Head (CH) 2.3+0.36 2.28+0.36 Thoracic Inlet (TI) 6.32+1.07 5.99+0.62 Anterior Mediastinum (AM) 2.53+0.82 1.89+0.82 APWI (TI X AM) 16.2+6.77 11.1+4.4* *p=0.015
Conclusion:
ECM is straightforward, safe, and accurate in mediastinal staging. Our novel APWI helps to safely select patients for any thoracic surgeon's skill and comfort level.
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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: 2
- Moderators:J.M. Clavero, R. Hassan
- Coordinates: 9/08/2015, 16:45 - 18:15, 702+704+706
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MINI25.09 - Percutaneous Cryoablation for Recurrent Mesothelioma following Lung Sparing Pleurectomy and Decortication: Safety and Efficacy (ID 3206)
17:30 - 17:35 | Author(s): R.B. Cameron
- Abstract
- Presentation
Background:
Percutaneous cryoablation (PC) is an ablative technique, being used for local treatment of recurrent mesothelioma in patients following surgical lung sparing decortication and pleurectomy, and occasionally for palliative control of tumor extension to vital structures or pain control. The purpose of this study was to evaluate the safety and efficacy of PC in local control of recurrent mesothelioma.
Methods:
With IRB approval, patients with recurrent mesothelioma following lung sparing pleurectomy and decortication with at least one PC were identified from a database containing ablation information. Intra procedural and immediate post procedural hospital information was assessed for complications and follow up imaging was used to asses for late complications and recurrence. Patients were followed with CT and and PET/CT scans for 6 and some up to 12 months. Local recurrence determined by increased regional metabolic activity or increased size of post ablation zone at 6 months. A stepwise multiple logistic regression model was used to assess predictors of local recurrence after ablation, considering clinical variables including: stage at diagnosis, chemotherapy, radiation, recurrence time lag following surgery, and number of lesions at time of recurrence presentation, And PC variables including: size of the lesion, edge of ice ball beyond the tumor, number of probes, size of probes, number of cryo cycles, maximum and total freeze and thaw time.
Results:
From the database, 25 patients were identified who underwent a total of 117 outpatient cryoablations (range of 1-25). 4 ablations in 3 patients were performed for palliative and pain control indications. Lesions measured a mean of 32.5 mm (range 9-113) by 18.0 mm (range 6-60) in diameter. At 6 months 110/117 (94.0%) of ablations showed no recurrence. No major, but minor complications including hematoma, small pneumothorax and hemoptysis in one patient each and erythema in 3 chest wall subcutaneous lesions (5/117 =4.2%). Late complications in 4/117 (3.4%) ablations. Considering the clinical and cryoablation variables no recurrence was seen in patients having the edge of iceball more than 7 mm beyond the tumor.
Conclusion:
PCT can be used for management of recurrent mesothelioma following surgery with low recurrence rate of 6%, and limited procedural complications 4.2% and late complications of 3.4%. When performing PCT, at least 7 mm of the of iceball is needed to extend beyond the edge of tumor to limit local recurrence.
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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): R.B. Cameron
- 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): R.B. Cameron
- 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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ORAL 13 - Immunotherapy Biomarkers (ID 104)
- Event: WCLC 2015
- Type: Oral Session
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:D. Kim, D. Grunenwald
- Coordinates: 9/07/2015, 16:45 - 18:15, Four Seasons Ballroom F3+F4
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ORAL13.02 - Characterization of PD-L1 Expression Related to Unique Genes in NSCLC Tissue Samples (ID 2173)
16:56 - 17:07 | Author(s): R.B. Cameron
- Abstract
- Presentation
Background:
Programmed cell death protein 1 (PD-1) receptors are members of the B7:CD28 family that interact with PD-1 ligands PD-L1 and PD-L2 to regulate cytotoxic T cell (CTL) tolerance (Freeman, J Exp Med. 2000; Latchman, Nat Immunol. 2001). Successful evasion of transformed cells from host defense is a feature of cancer (Hanahan, Cell 2011). Immune evasion can occur via the engagement of PD-1 with PD-L1 or PD-L2 (Dong, Nature Med 2002). In metastatic non-small cell lung cancer (NSCLC), PD-L1 expression has been associated with increased response to inhibitors of PD-1 (Garon, NEJM 2015). Current adjuvant cytotoxic approaches are associated with a real but small survival increases and significant toxicity. Characterization of PD-L1 expression in resected tumors could guide development of immune checkpoint based adjuvant trials.
Methods:
Microarray analyses were performed to assess gene expression for 320 NSCLC and 15 normal lung resection specimens profiled on the Agilent Whole Human Genome 4x44K 2-color platform. The reference sample used in the experiments was an equal mixture of 258 of the 320 NSCLC samples included in the study. Microarray data was imported into Rosetta Resolver for analysis. The Rosetta Similarity Tool (ROAST) was utilized to find genes correlated to PD-L1 expression. Both PD-L1 and the target gene had to be differentially expressed for sample to be included in computation of correlation. Cosine correlation was used as the similarity metric. Functional genomic analysis on the list of PD-L1 correlated genes was performed using tools available with the DAVID Bioinformatics resources (david.abcc.ncifcrf.gov) Survival analyses based on PD-L1 expression were performed using the Kaplan-Meier method and compared using the log-rank test. Samples with PD-L1 log(ratio) > 0 and p-value < 0.01 were classified as upregulated, samples with p-value>0.01 were classified as unchanged, and sample with log(ratio) < 0 and p-value <0.01 were classified as downregulated.
Results:
The reference level of PD-L1 expression among the subset of normal lung and NSCLC tissue samples was higher compared to levels seen in 503 breast cancer and 149 endometrial cancer tissue samples. Within the 320 NSCLC tissue samples, 174 unique genes are highly correlated with PD-L1 expression (r range= 0.692-0.904). 80 tissue samples (25%) had a PD-L1 log ratio > 0, and 63 tissue samples had large sets of highly correlated genes, a similar prevalence to membranous staining in half the cells in metastatic NSCLC (Garon, NEJM 2015). Functional analyses revealed that the genes significantly correlated with PD-L1 expression were involved in immune and inflammatory response. No significant difference in overall survival was noted (p=.661), but increased PD-L1 expression was clearly not associated with better outcomes.
Conclusion:
Within the NSCLC cohort, there is a group of patients with high expression for PD-L1 and related genes. This group does not have a better prognosis in comparison to those with typical or decreased PD-L1 expression. Due to the relationship between PD-L1 expression and response to anti-PD-1 therapy in metastatic NSCLC, this data and its correlation with other clinical characteristics of the patients can guide the design of adjuvant approaches based on immune checkpoint inhibitors.
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