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D. Jablons
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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: 15
- Moderators:D. Jablons, B. Stiles
- Coordinates: 9/08/2015, 16:45 - 18:15, 605+607
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MINI19.01 - Benefits of Surgical Treatment and Complementary Utility of Metabolic Tumor Volume in Selecting Therapy for Stage III NSCLC (ID 3143)
16:45 - 18:15 | Author(s): L. Xiong, K. Wroblewski, Y. Jiang, R. Salgia, H. Macmahon, M. Ferguson, Y. Pu
- Abstract
- Presentation
Background:
Stage III NSCLC has large variations in primary and nodal metastatic tumor burden and its treatment is controversial.We determined the benefit to overall survival (OS) of these patients from surgery, and potentially complementary role of FDG-PET/CT-based metabolic tumor volume of primary tumor (MTV~T~), nodal metastasis (MTV~N~), and whole-body (MTV~WB~) in selecting patients for surgery.
Methods:
With IRB approval, we retrospectively reviewed 239 stage III NSCLC cases with pre-therapy FDG-PET/CT scans treated 2004 – 2013 (141 IIIA and 98 IIIB, 115 men and 124 women, median age 67.2 years), and measured MTV~T~,MTV~N~, and MTV~WB~. Kaplan-Meier curves and log-rank test were used for determining survival differences between surgically and non-surgically treated patients. Multivariate Cox regression analyses were conducted. Logistic regression analysis was used to evaluate whether each covariate was associated with receiving surgery(including surgery alone and surgery in combination with chemo or radiation). Wilcoxon rank-sum tests were performed for determining differences of primary, nodal, and whole-body MTV between the groups.
Results:
30% (42/141) of IIIA patients and 10% (10/98) of IIIB patients had surgical treatment (p<0.001, Chi-square test). OS was different between surgically and non-surgically treated patients (p<0.001) at 1 year(86% vs. 54%), 2 years(64% vs. 32%), 3 years(52% vs. 21%), and 5 years(39% vs. 14%), with median survival of 37.3 months vs.13.6 months, respectively. Covariates associated with OS were: surgery (0.43 ≤ HR ≤ 0.46, p≤0.001), log~10~MTV~T~ (HR=1.54, p<0.001), log~10~MTV~N~ (HR=1.63, p<0.001), and log~10~MTV~WB~ (HR=2.06, p<0.001) (Figure 1). Log~10~MTV~T~, Log~10~MTV~N~, and Log~10~MTV~WB ~were inversely associated with receiving surgery, with odds ratio of 0.53(p=0.01), 0.55(p=0.036), and 0.38 (p=0.002), respectively. MTV~T~, MTV~N~, and MTV~WB~ were smaller in surgically treated patients, with median of surgically vs. non-surgically treated patients of 17.8 vs. 55.0, 5.3 vs. 15.1, and 27.8 vs. 92.0 cc, respectively (p≤0.004). Additionally, those with stage IIIB disease were significantly less likely to receive surgery after controlling for age, gender, and MTV. No statistically significant interactions were found between surgery and stage or between surgery and log~10~MTV~T~, log~10~ MTV~N~, or log~10~MTV~WB~.Figure 1
Conclusion:
Surgery and smaller MTV are associated with better OS of stage-III NSCLC patients. Smaller MTV and stage IIIA (vs. IIIB) are associated with receiving surgery. FDG PET/CT-based metabolic tumor volume can potentially inform surgical treatment decisions to further improve survival outcome.
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MINI19.02 - Mediastinal Nodal Involvement in Patients with Clinical Stage I Non-Small-Cell Lung Cancer - Possibility of Rational Lymph Node Dissection - (ID 2320)
16:45 - 18:15 | Author(s): T. Haruki, K. Aokage, T. Miyoshi, T. Hishida, G. Ishii, J. Yoshida, M. Tsuboi, H. Nakamura, K. Nagai
- Abstract
- Presentation
Background:
Recent developments of radiological examinations have been able to bring more accurate information about the biological malignancy of primary tumors in non-small cell lung cancer (NSCLC). The aim of this study is to elucidate the optimal candidate of lobe-specific selective lymph node dissection (LND) that reduces the extent of mediastinal LND according to clinical information including radiological evaluation of primary tumor on thin-section computed tomography (TSCT) and tumor location in clinical(c)-stage I NSCLC patients.
Methods:
Eight hundred and seventy-six patients with c-stage I NSCLC (adenocarcinoma and squamous cell carcinoma), who underwent complete surgical resection between January 2003 and December 2009 were included in this study. For all tumors, we obtained the maximum dimension of the tumor (tumor) and solid component (consolidation) using a lung window level setting from the TSCT scan images, and estimated the consolidation-to-tumor ratio (C/T ratio) for each tumor. We elucidated the lymph node metastatic incidence and distribution according to the primary tumor lobe location and extracted the associated clinicopathological factors with mediastinal lymph node involvement.
Results:
The patients included 490 men and 386 women, with a median age of 66 years old. The radiological findings were ground glass opacity (GGO)-predominant (C/T ratio ≤ 0.5) in 134 patients and solid-predominant (C/T ratio > 0.5) in 742 patients. There were 744 adenocarcinoma cases and 132 squamous cell carcinoma cases, and the incidences of mediastinal lymph node metastasis were 9.9% in adenocarcinoma cases and 4.5% in squamous cell carcinoma cases, respectively. There were no cases with hilar and mediastinal lymph node metastasis in GGO-predominant tumors. There was no significant association of clinical factors with subcarinal lymph node metastasis in right upper-lobe and left upper-division lung adenocarcinoma. In 257 bilateral lower-lobe lung adenocarcinomas, a total of 32 cases (12.5%) were positive for mediastinal lymph node metastasis, and seven cases (2.7%) were negative for subcarinal lymph node metastasis but positive for upper mediastinal lymph node metastasis (mediastinal skip metastasis). An elevated preoperative serum carcinoembryonic antigen (CEA) level (p < 0.001) showed only a significant association with upper mediastinal lymph node metastasis in the patients with bilateral lower-lobe primary lung adenocarcinoma.
Conclusion:
It would be acceptable to perform selective LND in patients with c-stage I NSCLC with GGO-predominant tumor. Elevated serum CEA was associated with upper mediastinal lymph node involvement in lower-lobe primary lung adenocarcinoma with radiologically solid-predominant tumor. We should be careful when applying selective LND to patients with solid-predominant tumor, especially located in the lower lobe.
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MINI19.03 - Subcarinal Lymph Node Dissection Is Also Necessary in Upper Lobectomies for Lung Cancer (ID 596)
16:45 - 18:15 | Author(s): J. Eckardt, E. Jakobsen, P.B. Licht
- Abstract
- Presentation
Background:
Mediastinal lymph node evaluation in Non Small-Cell Lung Cancers (NSCLC) is of paramount importance for optimum planning of treatment. Recently, it was claimed that subcarinal lymph node dissection could be spared in upper lobe NSCLC resections because of the low incidence of metastatic disease. These data, however, were single institution reports. We used complete national data to investigate patterns of unsuspected mediastinal lymph node involvement in patients operated for NSCLC.
Methods:
A national registry was used to identify every single patient operated for NSCLC during an 11-year period (2003-2013). Unsuspected mediastinal lymph node involvement was investigated by comparison of clinical and final pathological nodal stage, and patients with clinical mediastinal lymph node metastases were excluded. For every patient we extracted information about tumor location, histopathology, clinical and pathological TNM-stage. All preoperative imaging and staging investigations were recorded.
Results:
An unsuspected mediastinal lymph node metastasis was found in 426 patients (9.8%) of 3953 patients and 167 (4.4%) had unsuspected subcarinal metastases, which were significantly more frequent in patients with lower lobe or middle lobe cancers compared with upper lobe cancers 7 % (101/1440) versus 1.8% (42/2258), (p<0.01). Preoperative invasive mediastinal staging was used in 57% (n=2253) of all patients and significantly more frequent in upper lobe cancers (62% (n=1400), p<0.01), in patients who had unsuspected mediastinal lymph node metastasis (75% (n=320), p< 0.01) and in patients with subcarinal metastases (74% (n=124), p< 0.01).Location of the tumor All patients Patients with N2 disease Metastasis in station 7 RUL 1254 121 28 (2.2 %) LUL 1004 116 14 (1.4 %) RLL 672 78 52 (7.7 %) LLL 585 62 36 (6.2 %) Middle lobe 183 16 13 (7.1 %) Bilobectomy 255 33 24 (9.4 %) Total 3953 426 167
Conclusion:
A substantial number of patients undergoing surgery for NSCLC have unsuspected subcarinal mediastinal lymph node involvement despite 74% had preoperative invasive mediastinal staging. Unsuspected subcarinal metastases were most common in lower and middle lobe cancers but were also frequent in upper lobe NSCLC. Subcarinal lymph node dissection should therefore be a routine part of surgery for NSCLC - regardless of tumor location to avoid undiagnosed subcarinal lymph node metastasis.
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MINI19.04 - Relationship Between Adequacy of Intra-Operative Lymph Node Sampling During Surgical Resection of NSCLC and Survival (ID 1239)
16:45 - 18:15 | Author(s): M. Evison, S. Britton, H. Al-Najjar, R. Shah, P. Crosbie, R. Booton
- Abstract
- Presentation
Background:
Intra-operative lymph node sampling during lung cancer resection is a key surgical performance measure. It informs prognosis, treatment selection for adjuvant chemotherapy and surveillance programs following treatment. This study aimed to analyse the relationship between adequacy of intra-operative lymph node sampling and survival at a large thoracic oncology centre in the United Kingdom.
Methods:
A retrospective review of pathological reports for all patients undergoing lung cancer resections at the University Hospital South Manchester from 01/01/2011 to 31/12/2013 was undertaken. Intra-operative lymph node sampling was assessed for adequacy against standards set out by the IASLC Staging Manual in Thoracic Oncology. Survival data was obtained through national death registry data and provided a minimum of twelve months follow-up for all patients at the time of analysis in January 2015.
Results:
A total of 987 patients underwent surgical resection for NSCLC in the study period. Overall, there was no significant difference in survival between patients with adequate intra-operative lymph nodal sampling and those with inadequate sampling (log rank p=0.66). Median survival times were not estimable for pN0 and pN1 patients as only a small proportion died. However there was a significant difference in the median survival time of pN2 patients according to whether the intra-operative lymph node sampling was adequate or inadequate (Figure 1). Figure 1Figure 2
Conclusion:
Few patients have died in the pN0 and pN1 categories limiting interpretation. As the data matures we expect to see a survival difference according to adequacy of intra-operative nodal sampling that is supported by the differential median survival data of pN2 patients according to nodal adequacy. The data supports that the survival difference is due to inaccurate staging, inadequate resection (R1) and inappropriate omission of adjuvant.
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MINI19.05 - Discussant for MINI19.01, MINI19.02, MINI19.03, MINI19.04 (ID 3548)
16:45 - 18:15 | Author(s): M. Weyant
- Abstract
- Presentation
Abstract not provided
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MINI19.06 - External Validation of a Chinese Developed Survival Score in a Western Cohort Undergoing Surgery for Non-Small Cell Lung Cancer (ID 2226)
16:45 - 18:15 | Author(s): U. Kumbasar, H. Raubenheimer, M. Al Sahaf, N. Asadi, M.E. Cufari, C. Proli, P. Perikleous, L. Azcarate, Z. Niwaz, E. Beddow, V. Anikin, N. McGonigle, S. Jordan, G. Ladas, M. Dusmet, E. Lim
- Abstract
- Presentation
Background:
Currently adjuvant chemotherapy is not recommended for patients with completely resected stage I lung cancer. The ability to sub-stratify survival within stage I is an important consideration as it is assumed that survival is heterogeneous within this sub-group. Liang et al recently published a Chinese multi-institutional logistic regression derived model to predict post-operative survival in over 5000 patients undergoing lung cancer surgery for all stages. The aim of our study is external validation of their published nomogram in a British cohort focusing on stages IA and IB to determine applicability in selection of adjuvant chemotherapy within stage I.
Methods:
We retrospectively analysed data from a prospectively collected database from our institutions. Patient variables were extracted and the score individually calculated. Receiver operative characteristics curve (ROC) was calculated and compared with the original derivation cohort and the discriminatory ability was further quantified using survival plots by splitting our (external) validation cohort into three tertiles and Kaplan Meier plots were constructed and individual curves tested using Cox regression analysis on Stata 13 and R 3.1.2 respectively.
Results:
From April 2007 to February 2015 a total of 1442 patients underwent surgery for primary lung cancer at our institution. We excluded 118 patients with carcinoid tumours (not in the original Chinese development set) and 86 patients without complete lymph node assessment leaving 1238 patients for validation. For all patients from stage IA to IIB the mean (SD) score was 9.95 (4.2). The ROC score comparing patients who died versus those that remained alive was 0.62 (95% CI 0.58 to 0.67). This was lower than the 0.71 reported by the Chinese group when split into 1,3 and 5 year survival. When divided into prognostic score tertiles, survival discrimination remained evident for the entire cohort, as well as those for stage IA and IB alone. The P value comparing survival between the middle and highest score with baseline (low score) was P=0.031 and P=0.034 respectively. Figure 1. Survival discrimination within Stage I Figure 1
Conclusion:
Our results of external validation suggested lower survival discrimination than reported by the original group, however discrimination between survival remained evident for stage I.
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MINI19.07 - ICG Fluorescence Localization of Small Sized Pulmonary Nodules for VATS (ID 70)
16:45 - 18:15 | Author(s): T. Anayama, K. Hirohashi, R. Miyazaki, H. Okada, M. Kume, N. Kawamoto, T. Sato, K. Orihashi
- Abstract
- Presentation
Background:
Video-assisted thoracoscopic wedge resection of multiple small, non-visible, and nonpalpable pulmonary nodules is a clinical challenge. We propose an indocyanine green (ICG) injection and intraoperative fluorescence detection with a near-infrared (NIR) fluorescence for localization of small sized pulmonary nodules.
Methods:
Fluorescence properties of ICG topically injected into the lung parenchyma were determined using a resected porcine lung and previously reported by the authors. In clinical study, 15 cases of VATS pulmonary resection for small sized pulmonary nodules were enrolled in the study. The ICG mixed with iopamidol was injected into the pulmonary nodules by CT-guided percutaneous injection. ICG fluorescence was visualized by a near-infrared (NIR) thoracoscope, then the target nodule was excised by VATS procedure.
Results:
Topically injected ICG / iopamidol mixture spot remained at the injected point of the lung parenchyma for more than 6 hours in each case, and each ICG fluorescence was identified at the pulmonary nodule with the NIR thoracoscope. Each target nodule was successfully removed with negative surgical margin.
Conclusion:
CT guided ICG injection and intraoperative NIR thoracoscopic detection is a feasible method to localize small sized pulmonary nodules.
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MINI19.08 - Validation of a Surgical Predictive Score for 90 Day Mortality in Lung Cancer and Comparison with Thoracoscore (ID 2754)
16:45 - 18:15 | Author(s): E.L. O'Dowd, T. McKeever, D.R. Baldwin, H.A. Powell, R.B. Hubbard
- Abstract
- Presentation
Background:
Current British Thoracic Society (BTS) guidelines advocate the use of a global risk prediction score such as Thoracoscore to estimate the risk of death prior to radical surgical management in those with non-small cell lung cancer (NSCLC). A recent publication by Powell et al(1) used the National Lung Cancer Audit (NLCA) linked to Hospital Episode Statistics (HES) to produce a score to predict 90 day mortality. The aim of this study is to validate this score, henceforth called the NLCA score, and compare its performance with Thoracoscore.
Methods:
We identified data on all patients in the NLCA who received curative surgery for NSCLC between 2010 and 2012. We calculated the proportion that died in hospital and within 90 days of surgery. Each person was given a score based on the coefficients and constants in the NLCA score and Thoracoscore. The discriminatory power of both scores was assessed by a receiver operating characteristic (ROC) and an area under the curve (AUC) calculation.
Results:
We identified 2858 patients for whom we had complete data to form our validation cohort. The 90 day mortality was 5%. We generated ROC curves to assess the discrimination of the NLCA score in predicting 90 day mortality and to test the ability of Thoracoscore to predict in-hospital mortality. Area under the ROC curve was 0.68 and 0.60 respectively. We performed a post hoc analysis using data from the NLCA on all 15554 patients who underwent curative surgery for NSCLC between 2004 and 2012 to derive summary tables for 90 day mortality, stratified by procedure type, age and performance status (table 1).
Conclusion:
These results suggest that although the NLCA score performs slightly better than Thoracoscore neither performs well enough to be advocated for routine use to risk stratify patients prior to lung cancer surgery. It may be that the addition of physiological parameters to demographic and procedural data or use of physiological measurements alone would better predict mortality; however this would form the basis of a further project. In the interim we advocate the use of our summary tables that serve to provide clinicians and patients the real-life range of mortality according to performance status and age for both lobectomy and pneumonectomy. 1. Powell HA, Tata LJ, Baldwin DR, Stanley RA, Khakwani A, Hubbard RB. Early mortality after surgical resection for lung cancer: an analysis of the English National Lung cancer audit. Thorax. 2013;68(9):826-34. Figure 1
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MINI19.09 - Adjunct Intraop Cone Bean CT (CBCT) with Real Time 3D Overlay Improves Diagnostic Accuracy of Electromagnetic Navigational Bronchoscopy (ENB) (ID 1078)
16:45 - 18:15 | Author(s): S. Sachidananda, J.E. Hasson, G. Avignon, C.G. Alvarado
- Abstract
- Presentation
Background:
ENB is limited by diagnostic accuracy of 60-80%[ [1]]. We hypothesize that using intraoperative CBCT with real time 3D overlay onto fluoroscopic images to confirm placement of biopsy tools in the lesion will increase the diagnostic accuracy of ENB biopsies. [1] Wang Memoli JS, Nietert PJ, Silvestri GA. Meta-Analysis of Guided Bronchoscopy for the Evaluation of the Pulmonary Nodule. Chest. 2012;142(2):385-393. doi:10.1378/chest.11-1764
Methods:
Patients with undiagnosed small pulmonary nodules (<20 mm) underwent biopsy where an initial CBCT of the chest under breath hold was performed, followed by a 3D model reconstruction of the lesions while the surgeon started the ENB. At the end of the bronchoscope navigation, the 3D model of the lesion was fused and automatically registered in real time over the 2D fluoroscopy, allowing an evaluation of the biopsy tool positioning in 3-dimensions. Multiple samples were collected after confirmation of the tool position using various oblique views. Figure 1
Results:
In our initial experience with 10 cases, CBCT acquisition, reconstruction and 3D-overlay was successful in all cases. This procedure enabled confirmation of biopsy tool position within the target lesion in all cases. In one case, the new information obtained successfully discriminated a diaphragm implant from what previously had been interpreted as a basilar parenchymal nodule. In a second case, CBCT reconstruction enabled biopsy of a 15mm lesion thought to be a solitary metastasis. The biopsy was interpreted as normal, albeit in clinical circumstances which were suspicious for malignancy. The patient elected non-surgical treatment of an esophageal primary, precluding definitive pathologic confirmation. A third case provided a biopsy interpreted as normal in a patient who ultimately proceeded to resection for growth of the nodule. While frozen section suggested a benign entity, final pathology demonstrated scattered elements of malignancy. In the remaining cases, CBCT and 3D overlay assisted in successful and accurate biopsy of nodules <20mm.
Conclusion:
Intraoperative CBCT and real time 3D overlay onto fluoroscopic images to confirm appropriate positioning of the biopsy tools in the lesion during ENB is technically feasible. It effectively combines the advantage of real time CT imaging with the advantages of ENB biopsy. This has the potential to increase the diagnostic accuracy of ENB aided tissue diagnosis of small pulmonary nodules. This novel technique will facilitate early accurate diagnosis of lung cancer in small nodules with a minimally invasive approach.
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MINI19.10 - Discussant for MINI19.06, MINI19.07, MINI19.08, MINI19.09 (ID 3544)
16:45 - 18:15 | Author(s): C. Manegold
- Abstract
- Presentation
Abstract not provided
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MINI19.11 - Use of Electromagnetic Navigational Bronchoscopy to Localize Pulmonary Nodules Prior to Minimally Invasive Sublobar Resection (ID 2303)
16:45 - 18:15 | Author(s): S. Sachidananda, J.E. Hasson, G. Avignon, C.G. Alvarado
- Abstract
- Presentation
Background:
Sublobar resection of small pulmonary nodules by minimally invasive techniques can be a challenge, as this approach reduces the haptic feedback often required to reliably localize small lesions. Use of Electromagnetic Navigational Bronchoscopy (ENB) is a relatively new technique that has potential to assist in real time operative localization of such lesions, as ENB can deliver visual cues for their location in the form of either a dye marking or a radio-opaque clip, or both. There is limited data available on the feasibility of this approach. We want to describe our experience with this technique.
Methods:
A retrospective review of cases in which ENB was used to localize small pulmonary nodules was done from August 1, 2013 to February 1, 2015. We start by using ENB to navigate to the target lesion. In our initial experience, methylene blue was injected into the parenchyma around the mass, and dye migration to the pleural edge was used as a visual cue for location. We then amended our protocol to include placement of both methylene blue dye and a radio-opaque clip in the parenchyma immediately adjacent to the target lesion. Fluoroscopy was then used to triangulate the location of the clip, and by extension the mass, via markings on the chest wall with the lung deflated prior to incision. The visual cue of the dye marking as well as the fluoroscopic localization of the clip served to confirm each other. This was followed by minimally invasive resection of the lesion using these cues to assist in port placement. Figure 1
Results:
A total of 28 cases were identified. ENB was successful in navigating to the lesion in all cases. ENB dye localization alone was successful in 5 of 6 cases. After the first unsuccessful dye localization, our amended protocol of dye marking and clip placement led to successful localization in 22 consecutive cases.
Conclusion:
Use of electromagnetic navigational bronchoscopy to localize small pulmonary nodules is a feasible approach and is technically straightforward. As we see broader implementation of lung cancer screening protocols, thoracic surgeons can expect to encounter many more small pulmonary nodules requiring resection. There is accumulating data that sublobar resection is equivalent to lobar resection for small, peripherally located lung cancer. Use of the algorithm – ‘Navigate, Triangulate and Resect’ will enable thoracic surgeons to more successfully perform sublobar resections of small pulmonary nodules by minimally invasive techniques.
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- Abstract
- Presentation
Background:
The rate of mediastinal lymph node metastasis is controversial for patients with clinical N0 non-small cell lung cancer. The primary advantage of video-assisted mediastinoscopic lymphadenectomy(VAMLA) over conventional mediastinoscopy or videomediastinoscopy is to reduce the false-negative rate. We aimed to analyze to evaluate the value of routine VAMLA for patients with clinical T1a-T2aN0 patients prospectively.
Methods:
From March 2010-January 2015, 41 patients with non-small cell lung cancer with clinical stage T1-T2aN0 by postireon emission tomography/computed tomography underwent routine VAMLA before planned resectional surgery.Routinely, stations #2L, 2R, #4R, #4L, 7 were nearly completely resected. In some patients, #10R and #8 lymph nodes were biopsied. The prevalence of mediastinal lymph node metastases at VAMLA and lung resection was recorded.
Results:
There were 5 females (12.2%) and 36 (87.8%) males. The mean age was 62.5 . years. A total of 5 patients were had cT1a-bN0, whereas 36 patients had T2aN0. Eleven patients (26.8%) had occult mediastinal lymph node metastasis. A total of 26 patients underwent lung resectional surgery; only one patient (3.8%) were upstaged to pN2, whereas 3 patients (11.5%) were upstaged to pN1.
Conclusion:
VAMLA seems to disclose considerable number of mediastinal lymph node metastasis in these patients with T1 and T2 clinically staged N0 by positron emission tomography/computed tomography. Routine use of VAMLA is recommended with limited use of mediastinal lymph node evaluation in patients during resectional surgery.
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MINI19.13 - Nodal Staging via Robotic-Assisted Thoracic Surgery for Clinical Stage I Non-Small Cell Lung Cancer (ID 1018)
16:45 - 18:15 | Author(s): V.M. Dipasquale, R.T. Hughes, S.C. Grant, B.E. Lally, W.J. Petty, A. Proto, L.J. Wudel
- Abstract
- Presentation
Background:
One measure of the quality of thoracic surgery for non-small cell lung cancer (NSCLC) is the adequacy of nodal evaluation; the rate of pathological nodal upstaging can introduce bias in patient selection for surgical therapy. Robotic-assisted thoracic surgery (RATS) offers the ability to sample nodal stations not easily assessed with conventional open surgical methods. We sought to determine the rate of nodal upstaging as a function of the frequency of various lymph node stations sampled in clinical stage I NSCLC patients undergoing RATS.
Methods:
We retrospectively reviewed the charts of patients with right-sided clinical stage I NSCLC who underwent robotic-assisted pulmonary resection with mediastinal lymph node dissection at our institution from 2013 to 2015. CT or PET scan was used to determine clinical stage. The DiPasquale Quality Index (DQI) defines a complete lymph node dissection (LND) as sampling LN 4R, 7, and 9 for right-sided tumors. Our institutional policy for the initial two years of our RATS program was to limit such to right-sided tumors.
Results:
Robotic anatomic lung resection was performed in 70 patients with right-sided clinical stage I NSCLC. The majority were of the upper lobe (41; 58.6%). The most frequent lymph node stations sampled robotically were LN 4R, 7, 9, 10, and 11 (60.6%, 90.1%, 66.2%, 49.3%, and 64.8%, respectively). According to the DQI, 31 (44.3%) tumors underwent complete LND. Pathologic nodal upstaging occurred in 5 patients (7.1% [pN1 4, 5.7%; pN2 1, 1.4%]). Hilar (pN1) upstaging occurred in 2.8%, 0%, and 20.0%, respectively, for cT1a, cT1b, and cT2a tumors. Comparatively, historic hilar upstage rates of video-assisted thoracoscopic surgery (VATS) versus thoracotomy versus recent robotic data for cT1a, cT1b, and cT2a were 5.2%, 7.1%, and 5.7%, versus 7.4%, 8.8%, and 11.5%, versus 3.5%, 8.6%, and 10.8%, respectively. The 1-year overall survival was 97% and the disease-free survival was 98% at 1 year.
Conclusion:
When patients are appropriately selected and proper lymph node sampling is performed, the rate of upstaging with RATS is comparable to VATS and lower than thoracotomy. The rate of hilar upstaging with robotic resection, however, increases with increasing clinical T stage and appears superior to both VATS and thoracotomy for cT2a tumors. This also has implications for patients who may be considered for therapies like stereotactic radiation therapy. Larger studies comparing matched open, VATS, and robotic approaches are necessary to quantify long term survival and local failure rates.
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MINI19.14 - Survival After Sub-Lobar Resection for Early Stage Lung Cancer: Methodological Obstacles in Comparing the Efficacy to Lobectomy (ID 1583)
16:45 - 18:15 | Author(s): E. Taioli, R. Yip, I. Olkin, A. Wolf, D. Nicastri, C.I. Henschke, H.I. Pass, R. Flores
- Abstract
- Presentation
Background:
Surgery is the treatment of choice for early stage lung cancer (LC). While lobectomy (L) is the historic standard, whether long term outcomes of sub-lobar resection (SL) are comparable is still under debate. The only randomized trial was conducted 20 years ago; 5 subsequent meta-analyses showed inconclusive or conflicting results. We present a comprehensive review of the literature on 5 year-survival after SL compared to L for early stage LC.
Methods:
A priori inclusion criteria were: 1) observational studies, 2) L compared to SL for early stage LC, 3) at least CT staging, 4) 5-year survival reported. A Medline search through January 2015 resulted in 32 studies, representing 24 distinct datasets. The absolute difference in 5-year survival was calculated and plotted for each study.
Results:
There were 4,702 cases treated with L, 2,323 treated with SL. Of 20 studies reporting the reason for SL, 11 indicated that SL was performed because of comorbidities, or impaired cardiopulmonary function. Among all 24 studies, 4 showed no difference in 5-year survival, 13 favored L, and 7 favored SL (Figure 1). Of the two studies using propensity scores, one favored L and the other SL. No meta-estimate could be calculated due to high statistical heterogeneity. Of 21 studies reporting recurrence rate (Figure 2), 11 favored L and 10 favored SL. Figure 1
Conclusion:
Studies comparing 5-year survival rates of SL to L are heterogeneous, and traditional meta-analytic summary estimates of survival and recurrence could not be calculated. SL survival is often similar to L survival, despite the fact that SL is performed in patients with comorbidities or impaired cardiopulmonary function. New approaches to comparing L to SL survival are needed.
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MINI19.15 - Discussant for MINI19.11, MINI19.12, MINI19.13, MINI19.14 (ID 3475)
16:45 - 18:15 | Author(s): J.H. Pedersen
- Abstract
- Presentation
Abstract not provided
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MS 11 - New Approaches to Combined Modality Therapy for Stage III Disease (ID 29)
- Event: WCLC 2015
- Type: Mini Symposium
- Track: Treatment of Locoregional Disease – NSCLC
- Presentations: 4
- Moderators:D. Jablons, J.P. Van Meerbeeck
- Coordinates: 9/08/2015, 14:15 - 15:45, 605+607
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MS11.01 - The Future of Radiation Therapy in Combined Modality Therapy (ID 1896)
14:15 - 15:45 | Author(s): R. Dziadziuszko
- Abstract
- Presentation
Abstract not provided
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MS11.02 - Future Role of Surgery (Timing, Patient Selection, and New Techniques) (ID 1897)
14:15 - 15:45 | Author(s): W. Weder
- Abstract
- Presentation
Abstract:
The optimal management of locally advanced NSCLC is discussed controversially and depends from various aspects including the extend of N2 disease and/or T-stage as well as the patients risk profile and preference and the institutional experience. Therefore existing guidelines need a balanced modification during the tumorboard taking into account the different aspects relevant for the patient’s outcome and hence to define the best individualized treatment. Due to the lack of fully convincing randomized trials and the diversity of phase II studies and especially the heterogeneity of the study population, it is not surprising that the available evidence is interpreted differently and discussed controversially. Survival data may differ widely between studies and an explanation is often elusive. Patient selection is among other factors the key for differences in outcome. Unfortunately N2 disease is often imprecisely described. Several authors have proposed that N2 disease should be divided into subgroups. The question, whether N2 disease is resectable, cannot be answered easily in borderline situations since several co-founding factors play a role. The question includes at least four different aspects. The first aspect is resectability. The surgeon has to answer if the affected lymph nodes are completely removable. This question is a prerequisite and is typically answered by analysing images especially the CT or PET/CT by an experienced surgeon. The second and even more critical aspect relates to the question if local resection is useful for the patient since N2 disease may be the tip of an iceberg and indicate more than just locally advanced disease and rather a disease with systemic spread of tumor cells to other organs. The third aspect is the response rate of the tumor and mediastinal lymph nodes to neoadjuvant chemo- or chemo-radiotherapy. Finally the fourth consideration has to take into account the risk benefit ratio for the patient regarding the treatment. It is relevant for the decision making to evaluate to what risk the patient is exposed when a lobectomy or pneumonectomy is performed after neoadjuvant therapy. There are subgroups in stage IIIA (N2) which can be defined in which treatment recommendations are agreed among most oncologists, surgeons and radiotherapists. Microscopic N2 found unexpectedly during surgery and a radical resection of the tumor as well of the lymph nodes is possible and tolerated by the patient, surgery should be completed and adjuvant therapy is recommended. On the other hand in cases of bulky multilevel N2 at initial diagnosis and especially persistent after neoadjuvant therapy, surgery is not generally indicated since the patient will not experience a profit. The main controversy occurs in cases with initially diagnosed N2 disease at either a single or in some adjacent stations but surgically resectable. These patients are recommended to undergo neoadjuvant chemo- or chemo-radiotherapy followed by surgery most cases but direct surgery followed by adjuvant treatment is justified in single station N2 without extranodal disease. Definitive chemo-radiotherapy is reserved for those who are not completely resectable or with a high perioperative mortality. In general, these patients require a lobectomy with a complete mediastinal lymphadenectomy. In locally advanced stages, many surgeons still prefer to do these operations though a thoracotomy and in only a smaller percentage of patients can be operated minimal invasively by VATS. The invasiveness of the approach (VATS or open) is in any case of less importance than the completeness of the resection. Pneumonectomy should be avoided whenever possible and reconstructive techniques with bronchial-and or vascular reconstructions (sleeve resections) should be considered. These techniques can be done safely, even after induction chemo-or chemoradiotherapy. However, there are clear situation, when a pneumonectomy is necessary to achieve a complete resection and this should be considered, when the patient tolerates it functionally. Treatment of patients with locally advanced lung cancer is a challenge and requires the expertise of specialists from each discipline who respect the benefit and limitations of each individual technique in order to define the best individual treatment.
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MS11.03 - New Systemic Approaches (Targeted Therapies and Immune Therapies) (ID 1898)
14:15 - 15:45 | Author(s): H. Borghaei
- Abstract
- Presentation
Abstract:
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MS11.04 - Overview of Current International Randomized Trials (ID 1899)
14:15 - 15:45 | Author(s): S. Ekman
- Abstract
Abstract:
Overview Stage III non-small cell lung cancer (NSCLC) is a heterogeneous disease with regard to tumor extent, prognosis and treatment options. Surgery is indicated in some patients, but the majority of patients receive radiotherapy and chemotherapy alone. The standard of care for unresectable stage III NSCLC patients with a good performance status consists of concurrent chemoradiation. The chemotherapy regimen usually consists of a platinum doublet and radiation doses of at least 60 Gy is standard. The prognosis for these patients remains dismal with a median survival time of 15-22 months and the need for improved treatment approaches is urgent. The optimal choice of chemotherapy and radiation dose and the schedules for these have been under investigation but is still not clearly defined. Radiation dose escalation studies have not resulted in better outcomes and with potentially harmful effects. Clinical studies of targeted agents in unselected patient groups, including therapies against epidermal growth factor receptor (EGFR) and angiogenic factors, have not been successful. The recent advances in molecularly targeted therapies together with technological advances in radiotherapy opens up for novel treatment strategies with potentially improved outcomes and less toxicity. This presentation will give an overview of randomized studies incorporating new approaches to combined modality therapy in stage III disease, including immune therapy with PD-1/PD-L1 inhibitors, inhibitors of EGFR and ALK as well as proton radiotherapy.
Author of
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MINI 14 - Pre-Clinical Therapy (ID 119)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:L. Fernandez-Cuesta, A.F. Gazdar
- Coordinates: 9/08/2015, 10:45 - 12:15, Mile High Ballroom 2c-3c
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MINI14.13 - Small Molecule Demonstrates Potent Tumor Suppression by Inhibiting the PI3K/AKT Pathway in Non-Small Cell Lung Cancer (ID 721)
10:45 - 12:15 | Author(s): D. Jablons
- Abstract
- Presentation
Background:
The phosphoinositide 3-kinase (PI3K) / protein kinase B (AKT) / mammalian target of rapamycin (mTOR) pathway is frequently activated in many malignancies including non-small cell lung cancer (NSCLC). Dysregulation of this pathway leads drives oncogenic genes and imparts resistance to conventional chemotherapy. We identified a small molecule AKT pathway inhibitor as a potential lead compound.
Methods:
The AKT pathway inhibitor was tested in vitro on a panel of NSCLC cell lines A427, A549, NCI-H1703, NCI-H2170, NCI-H1650, and NCI-H1975. Cell viability was determined by MTS assay after 72 hours of drug treatment. Activation kinases in the PI3K/AKT/mTOR pathway was determined by western blot analysis.
Results:
Treatment with the PI3K/AKT pathway inhibitor caused potent concentration-dependent inhibition of cell proliferation with a half maximal inhibitory concentration (IC~50~) in the nanomolar range. Kirsten rat sarcoma (KRAS) mutant cell lines were the most sensitivity to the PI3K/AKT pathway inhibitor while epidermal growth factor receptor (EGFR) mutant cell lines were more resistant. Western blot analysis showed inhibition of AKT and mTOR phosphorylation at nanomolar concentrations.
Conclusion:
A novel small molecule AKT inhibitor inhibits growth of NSCLC cells in vitro, is potent against KRAS mutants, and shows promise as a small molecule targeted chemotherapy drug for NSCLC.
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MINI 23 - Lung Cancer Risk: Genetic Susceptibility and Airway Biology (ID 135)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Screening and Early Detection
- Presentations: 1
- Moderators:P.E. Postmus, R. Young
- Coordinates: 9/08/2015, 16:45 - 18:15, 401-404
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MINI23.13 - Extracellular Sulfatase SULF2: A Potential Biomarker for the Early Detection of Lung Cancer (ID 3079)
16:45 - 18:15 | Author(s): D. Jablons
- Abstract
- Presentation
Background:
The extracellular sulfatases (SULF1 and SULF2) are overexpressed in a wide assortment of human cancers. SULF2, in particular, has been shown to drive carcinogenesis in non-small cell lung cancer (NSCLC), malignant astrocytoma, and hepatocellular carcinoma. As extracellular enzymes that are both tethered to the cell membrane and secreted, the SULFs and their heparan sulfate proteoglycan (HSPG) substrates are present in the extracellular environment. We hypothesize that the blood levels of SULF2 can serve as biomarkers for the early detection of NSCLC and malignant astrocytoma. The primary goal of this study is to evaluate the patient tumor and blood samples for the presence of the SULF2 in order to develop novel biomarkers for the early detection of NSCLC.
Methods:
We identified patients who underwent lung resection for adenocarcinoma (ADC) (41 patients) or squamous cell carcinoma (SCC) (51 patients) at our institution from 2000 to 2006. We excluded patients with recurrent lung cancer, or less than 3 mm of invasive tumor on H&E slide. A section from each paraffin-embedded tissue specimen was stained with a monoclonal antibody to SULF2. A pathologist determined the percentage (0-100%) and intensity (0-3) of tumor cells staining. Survival analysis was performed using a multivariate Cox proportional hazards model. We developed an ELISA to detect SULF2 in human blood. After testing a number of different strategies including using different combinations of our anti-SULF2 mAbs, we determined that a sandwich ELISA with capture mAb 5C12 followed by detection with biotinylated mAb 8G1 was best for the most sensitive detection of SULF2.
Results:
SULF2 staining (either tumor or stroma) was positive for 82% of the samples The SCC samples had a higher mean percentage of tumor staining compared to the ADC samples (100% vs. 60%; p<0.0005). However, after adjusting for age, sex, race, histologic type, stage, and neoadjuvant therapy, there was no significant association between percentage of SULF2 tumor staining and overall survival. Nonetheless, these initial findings are very encouraging, because the vast majority of ADC samples, including early stage disease, and all of the SCC tumor samples have some degree of staining for SULF2 protein. Using our SULF2 ELISA assay, we analyzed plasma samples from 54 healthy donors and 85 patients with newly diagnosed early stage NSCLC before surgical resection. The level of SULF2 protein is significantly higher in patients with NSCLC compared with healthy controls (738.4 ± 55.17, vs. 439.4 ± 40.88 pg/mL; p<0.0001).
Conclusion:
SULF2 protein was detected in the vast majority of tumor and blood samples of patients with lung cancer. Although additional studies are required, these data provide the first indication that SULF2 blood level may be a useful biomarker for the early detection of lung cancer.
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P1.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 233)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P1.04-058 - Inhibition of ERK1/2 Down-Regulates the Hippo/YAP Signaling Pathway in Human NSCLC Cells (ID 855)
09:30 - 17:00 | Author(s): D. Jablons
- Abstract
Background:
Alterations of the EGFR/ERK and Hippo/YAP pathway have been found in non-small cell lung cancer (NSCLC).
Methods:
Luciferase reporter and downstream gene expression assays were used to test hippo pathway activity.
Results:
Herein, we show that ERK1 and ERK2 have an effect on the Hippo/YAP pathway in human NSCLC cells. Firstly, inhibition of ERK1/2 by siRNA or small-molecular inhibitors decreased the YAP protein level, the reporter activity of the Hippo pathway, and the mRNA levels of the Hippo downstream genes, CTGF, Gli2, and BIRC5. Secondly, degradation of YAP protein was accelerated after ERK1/2 depletion in NSCLC cell lines, in which YAP mRNA level was not decreased. Thirdly, forced over-expression of the ERK2 gene rescued the YAP protein level and Hippo reporter activity after siRNA knockdown targeting 3'UTR of the ERK2 gene in NSCLC cells. Fourthly, depletion of ERK1/2 reduced the migration and invasion of NSCLC cells. Combined depletion of ERK1/2 had a greater effect on cell migration than depletion of either one separately. Finally, the MEK1/2 inhibitor Trametinib decreased YAP protein level and transcriptional activity of the Hippo pathway in NSCLC cell lines.
Conclusion:
Our results suggest that ERK1/2 inhibition participates in reducing YAP protein level, which in turn down-regulates expression of the downstream genes of the Hippo pathway to suppress migration and invasion of NSCLC cells.
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P1.08 - Poster Session/ Thymoma, Mesothelioma and Other Thoracic Malignancies (ID 224)
- Event: WCLC 2015
- Type: Poster
- Track: Thymoma, Mesothelioma and Other Thoracic Malignancies
- Presentations: 1
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P1.08-016 - Ponatinib Shows Promise in Malignant Pleural Mesothelioma Cells with Abl Pathway Dysregulation (ID 723)
09:30 - 17:00 | Author(s): D. Jablons
- Abstract
Background:
Malignant pleural mesothelioma (MPM) remains a lethal cancer with limited treatment options. Various tyrosine kinases including c-Abl/Arg, FGFR1, Src and PDGFRa/b have been implicated in driving the growth of MPM. Ponatinib is an FDA approved potent multi-target inhibitor of cAbl/Arg, PDGFRα, VEGFR2, FGFR1, and Src. The aim of this study was to investigate the effects of ponatinib on MPM cells.
Methods:
The in vitro effect of ponatinib on different MPM cell lines (H2052, MSTO211H, H2452, H28) were evaluated by MTS assay and the effect on cell migration was determined using a “scratch wound” assay. Levels of phosphorylated-Crkl (pCrkl) were evaluated by western blot and double-strand DNA breaks (DSDBs) measured via the surrogate marker γ-H2AX in an ELISA assay. A xenograft MPM model was used to examine the effects of ponatinib on tumor grown in vivo.
Results:
High levels of pCrkl were expressed in all MPM cell lines studied indicating c-Abl/Arg pathway activation. In vitro, ponatinib was effective against all MPM cell lines by cytotoxicity assay, led to dramatic cell migration inhibition, significantly reduced pCrkl expression, and increased DSDBs. In vivo, ponatinib blunted tumor growth in a xenograft model. Reduced pCrkl levels were observed in xenograft tumor specimens following ponatinib treatment.
Conclusion:
Inhibition of Abl kinase activity with ponatinib is a potential therapeutic approach in MPM patients with Abl pathway dysregulation. pCrkl shows promise as a biomarker of increased Abl kinase activity and may be useful in identifying MPM patients most likely to benefit from ponatinib.
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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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P3.04-089 - Prospective Use of Prognostic Molecular Assay Identifies Patients at Risk for Recurrence and Changes Clinical Management in Early-Stage NSCLC (ID 1497)
09:30 - 17:00 | Author(s): D. Jablons
- Abstract
Background:
Adjuvant chemotherapy recommendations depend on identification of early-stage non-small-cell lung cancer (NSCLC) patients at high-risk of recurrence. Current National Comprehensive Cancer Network (NCCN) guidelines use certain clinicopathologic features to make this recommendation for stage Ib-IIa patients. An internationally validated, 14-gene expression assay has been shown retrospectively to better stratify mortality risk in non-squamous NSCLC than conventional staging.
Methods:
Following up on a previously reported cohort of 52 patients, prospective molecular risk-stratification by the 14-gene test was performed in 66 patients with a mean follow up of 20.7 ±14.1 months. Disease-free survival and lung cancer mortality rates were compared between high- and low-risk patients by both molecular risk-stratification and NCCN “high-risk” characteristics.
Results:
Patients with low-, intermediate-, and high-risk based on molecular testing had recurrence rates of 4%, 8%, and 28% (p=.031, Fisher’s exact test) and lung cancer mortalities of 0%, 0%, and 16% (p=.039), respectively. Molecular high-risk was associated with shorter disease-free survival (p=.043, Kaplan-Meier log-rank). Molecular risk assessment was discordant from NCCN “high-risk” features in 15 of 25 stage Ib-IIa patients (60%). NCCN criteria failed to significantly predict either recurrence or mortality with recurrence rates of 8% and 23% (p=.077, Fisher’s exact test) and lung cancer related mortality of 3% and 12% (p=.165) among patients with NCCN low- and high-risk features respectively. Molecular high-risk scores changed adjuvant chemotherapy recommendations in 3 of 10 (30%) patients who otherwise did not meet NCCN criteria for adjuvant chemotherapy.
Conclusion:
This study demonstrates that prospective application of a 14-gene prognostic assay significantly predicts differences in disease-free survival. This prognostic information differs from NCCN high-risk clinicopathologic features and has clinical utility in better informing adjuvant chemotherapy recommendations.
