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F.(. Kong
Moderator of
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MINI 36 - Imaging and Diagnostic Workup (ID 163)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Screening and Early Detection
- Presentations: 15
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MINI36.01 - Three-Dimensional Quantitative Computed Tomography Evaluation of Pulmonary Adenocarcinoma Using Image-Analysis Software (ID 772)
18:30 - 18:35 | Author(s): K. Aokage, K. Hata, H. Ohmatsu, J. Yoshida, G. Ishii, T. Hishida, M. Tsuboi
- Abstract
Background:
Several 2-dimensional computed tomography (CT)-based evaluation methods of small-sized lung adenocarcinomas have been reported as predictors of the disease invasiveness. They include the ratio of the maximum diameter of consolidation to the maximum entire tumor diameter (C/T ratio), tumor shadow disappearance rate on mediastinal window images (TDR), and visual estimation of the ratio of ground-glass opacity area (GGO-R). However, these measurements can be poorly reproducible due to possible inter-observer discrepancy, and can be unrepresentative because measuring is done only on one section of a lesion. We have developed a 3-dimensional quantitative entire-nodule evaluation method using novel image-analysis software. The aim of this study is to compare the new method to these 2-dimensional evaluation methods as a predictor of small-sized invasive lung adenocarcinomas.
Methods:
There were 101 consecutive patients with clinical stage IA adenocarcinoma of the lung who underwent complete resection between 2002 and 2005 at our institution, excluding patients undergoing preoperative treatment and those with multiple lung nodules or with a past history of other cancers. Of them, 75 had a nodule separated from the chest wall and mediastinum depicted on preoperative thin section CT scan without contrast enhancement, and they were the subject of this study. The reconstruction interval of the CT scans was 0.2mm and the reconstructed slice thickness was 0.5mm. The image analysis software recognizes a nodule as a collection of cubic voxels. Ground glass opacity (GGO) was defined as the area of increased attenuation in the lung with preservation of the bronchial and vascular margins. As the average CT value of pulmonary arteries on non-contrast-enhanced CT was 50 Hounsfield Unit (HU), we measured the percentage of the voxels over 50 HU in a nodule to identify voxels representing solid component, and the percentage was defined as R-50. Invasive cancer was defined as a nodule with pathological lymphatic permeation, vascular invasion or node involvement. The correlation between invasive lung cancer and clinicopathological factors, including the image findings (C/T ratio, TDR, GGO-R and R-50) was evaluated using multivariate analysis. The areas under the curve (AUC) of receiver operating characteristics curves were compared among the image evaluation methods.
Results:
There were 17 invasive cancers. C/T Ratio, TDR, GGO-R and R-50 were independent predictors of invasive lung cancers (p<0.01). R-50 was equivalent in AUC to the other evaluation methods (AUC: R-50, 0.807; C/T Ratio, 0.800; TDR, 0.809; GGO-R, 0.792, respectively).
Conclusion:
Our new 3-dimensional quantitative evaluation method using image-analysis software had invasive cancer predictability similar to the other 2-dimensional evaluation methods. As this method enables entire-tumor evaluation quantitatively and objectively, it should be more reproducible and reliable than the conventional methods.
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MINI36.02 - Newly Detected Solid Nodules at Incidence CT Lung Cancer Screening Rounds: Occurrence and Lung Cancer Probability (ID 1352)
18:35 - 18:40 | Author(s): J.E. Walter, M.A. Heuvelmans, G.H. De Bock, P.A. De Jong, R. Vliegenthart, M. Oudkerk
- Abstract
Background:
Lung cancer screening by low-dose computed tomography (LDCT) is now recommended for high-risk individuals by US guidelines. New nodules detected after initial baseline screening may complicate management. So far, reported results of new nodules have been inconsistent as different definitions were used. The purpose of this study was to determine the occurrence of new solid nodules and their respective lung cancer rate at incidence screening rounds of the Dutch-Belgian Randomized Lung Cancer Screening Trial (NELSON).
Methods:
The NELSON trial was approved by the Dutch Ministry of Health. All participants gave written informed consent. In total, 7,557 individuals underwent baseline LDCT screening. Incidence-screening rounds took place after 1, 3 and 5.5 years. This study included participants with solid non-calcified nodules, newly detected after baseline and also in retrospect not present on any previous screen. Lung cancer diagnosis was based on histology, and benignity was based on either histology or a stable size for at least two years. Nodule volume was generated semi-automatically by Lungcare software (Siemens, Erlangen, Germany), and the nodule detection limit was 15mm[3].
Results:
During the incidence screening rounds, 1,484 new solid nodules were detected in 949 participants (77% male), with a median age of 59 years (interquartile-range 55-63 years). At the second screening round (1 year after baseline), at least one new solid nodule was present in 4.7% (344/7,295) of participants, and at the third screening round (2 years after the second screening round) additional new nodules were found in 7.1% (491/6,922) of participants. Eventually, a new solid nodule was proven to be lung cancer in 7.9% (75/949) of participants with new solid nodules (77 cancers). A higher number of pack-years smoked increased the risk of a new nodule being cancer significantly (P=0.004). Age and gender distribution were comparable between participants with and without lung cancer detected in a new solid nodule (P=0.236 and P=0.157 respectively). The majority of cancers was diagnosed at stage I (48/77 [62.3%]). Most of the lung cancers were adenocarcinoma (30/77 [39.0%]), squamous cell carcinoma (20/77 [26.0%]) or small cell lung cancer (9/77 [11.7%]).
Conclusion:
New solid nodules are common findings in LDCT lung cancer screening and possess a comparably high risk of malignancy. Guidelines may need to consider a more stringent follow-up for new nodules. More research concerning new nodules is necessary to determine a sufficient follow-up strategy and evaluate distinguishing nodule features of benign and malignant new nodules.
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MINI36.03 - Multi-Nodularity in Baseline CT Lung Cancer Screening and Relationship with Lung Cancer Probability (ID 1392)
18:40 - 18:45 | Author(s): R. Peters, M.A. Heuvelmans, P. De Jong, P. Van Ooijen, M. Oudkerk, G. De Bock, R. Vliegenthart
- Abstract
Background:
Currently, there is little known about prevalence of multi-nodularity in a high risk screening population. Radiologists often find more than one nodule per screenee. Whether the number of lung nodules plays a role in the probability of lung cancer, remains still largely unknown.
Methods:
In the Dutch-Belgian randomized lung cancer screening trial (NELSON), launched in 2003, participants were selected with at least one non-calcified nodule at baseline. The NELSON trial was approved by the Ministry of Health and the ethics board of each participating center. All participants gave written informed consent. The per-participant number of baseline nodules was determined. The probability of lung cancer was compared for categories based on the number of baseline nodules, using chi-square testing. Lung cancer diagnosis was confirmed by histology. Nodules were classified as benign if they did not show growth for up to six years after baseline.
Results:
3,392 participants (84,4% male, median age 58 years, median pack years 37,9) with 7,258 nodules at baseline CT screening were included. Of these 3,392 screenees, 1,746 (51,5%) had one nodule, 800 (23,6%) had two nodules, 354 (10,4%) had three nodules, 191 (5,6%) had four nodules, and 301 (8,9%) had five or more nodules. The probability of lung cancer was 61/354 (3.5%) in subjects with one nodule, 37/800 (4.6%) in those with two nodules, 17/354 (4.8%) for three nodules, 12/191 (6.3%) for four nodules and 10/301 (3.3%) when a participant had over four nodules (p=NS). In the baseline screening round, 62 subjects had a malignant nodule. Lung cancer diagnosis was made in the nodule with the largest volume in 60/62 (96.8%) cases. Overall, lung cancer was diagnosed in 137/3,392 subjects (4.0%) in whom nodules were found at baseline. Mean nodule count in screened subjects with only benign nodules was 2.1±1.8, compared to 2.3±2.2 in those with a malignant nodule.
Conclusion:
At baseline CT lung cancer screening, nearly half of screened participants with lung nodules have more than one lung nodule. Nodule count did not have predictive value in the determination of lung cancer probability in lung cancer screening participants. In the first screening round, of all detected nodules per screenee, lung cancer was detected most frequently in the nodule with the largest volume.
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MINI36.04 - Automated Measurement of Malignancy Risk of Lung Nodule Detected by Screening Computed Tomography (ID 1737)
18:45 - 18:50 | Author(s): A.J. Ritchie, M. Tammemägi, C. Jacobs, J. Mayo, W. Zhang, H. Roberts, M. Gingras, S. Pasian, L. Stewart, S. Tsai, D. Manos, J.M. Seely, P. Burrowes, R. Bhatia, S. Atkar-Khattra, B. Van Ginneken, M.S. Tsao, S. Lam
- Abstract
- Presentation
Background:
We have previously reported a practical predictive tool that accurately estimates the probability of malignancy for lung nodules detected at baseline screening LDCT (New Engl J Med. 2013;369:908-17). Manual measurement of nodule dimensions and generation of malignancy risk scores is time consuming and subjected to intra- and inter-observer variability. The goal of this study is to prepare a nodule malignancy risk prediction model based on automated computer generated nodule data and compare it to an established model based on radiologists’ generated data.
Methods:
Using the same published PanCan dataset (New Engl J Med. 2013;369:908-17) with the number of lung cancers updated, we prepared a logistic regression model predicting lung cancer using computer-generated imaging data from the CIRRUS Lung Screening software (Diagnostic Imaging Analysis Group, Nijmegen, The Netherlands). Ninety-one of the 2,537 baseline (first) scans were not available or could not be processed by CIRRUS. The remaining 2,446 scans were first annotated by the CIRRUS software. A human non-radiologist reader then accepted/rejected the annotated marks and manually searched the LDCT for nodules missed by CIRRUS or the study radiologist. New nodules found that were not recorded by the study radiologist were reviewed by a subspecialty trained chest radiologist with 14 years experience in lung cancer screening (JM). Nodule morphometric measurements (maximum and mean diameter, volume, mass, density) and total nodule count per scan irrespective of size were automatically generated by the CIRRUS software. The nodule type (nonsolid, part-solid, or solid), nodule description (lobulated, spiculated or well defined) and nodule location (upper versus middle or lower lobe) were manually entered. The variables were evaluated in models as untransformed and natural log transformed variables. Nonlinear relationships with lung cancer were also evaluated. Socio-demographic and clinical history predictors were not included in the model.
Results:
Radiologists evaluation identified 8,570 pulmonary nodules of any size in 2063 individuals - 124 nodules in 119 individuals were diagnosed as cancer in follow-up. Based on CIRRUS software annotated marks that were accepted by a human reader, computer analysis identified 11,520 pulmonary nodules in 2174 individuals - 121 nodules in 115 individuals were diagnosed as cancer in follow-up. Thirty-six percent of new nodules found by CIRRUS and/or second human reader were ≥4 mm (mean±SD, 5.9± 3.5 mm). Both the computer generated imaging data model (Model-CIRRUS) and the radiologist generated data model (Model-RAD) demonstrated excellent discrimination and calibration. Their predictive performances were also similar. Comparing Model-CAD to Model-RAD, the AUCs were 0.9537 versus 0.9541, the 90[th] percentile absolute errors were 0.0008 versus 0.0007, and the Brier scores were 0.0093 versus 0.0137. Mean nodule diameter is a better risk predictor than maximum nodule diameter, nodule density or mass.
Conclusion:
The predictive performances of computer and radiologist generated data models were similar. The model can be integrated to the CIRRUS Lung Screening software to automatically generate a nodule malignancy risk score to facilitate nodule management recommendation. Supported by the Terry Fox Research Institute, The Canadian Partnership Against Cancer and the BC Cancer Foundation on behalf of the Pan-Canadian Early Detection of Lung Cancer Study Group.
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MINI36.05 - Computer Vision Tool and Technician as First Reader of Lung Cancer Screening CT (ID 1702)
18:50 - 18:55 | Author(s): A.J. Ritchie, C. Sanghera, C. Jacobs, W. Zhang, J. Mayo, H. Roberts, M. Gingras, S. Pasian, L. Stewart, S. Tsai, D. Manos, J.M. Seely, P. Burrowes, R. Bhatia, S. Atkar-Khattra, B. Van Ginneken, M. Tammemägi, S. Lam
- Abstract
- Presentation
Background:
The recommendation by the US Preventive Services Task Force to screen high-risk smokers with low-dose computed tomography (LDCT) and the recent decision by the Centers for Medicare and Medicaid Services to fund LDCT screening under the Medicare program mean that LDCT screening will be implemented at the population level in the US and likely in other countries. With the large volume of scans that will be generated, accurate and efficient interpretation of LDCT images is key to providing a cost-effective implementation of LDCT screening to the large at risk population. Objective To evaluate an alternative workflow to identify and triage abnormal LDCT scans in which a technician assisted by Computer Vision (CV) software acts as first reader with the aim to reduce workload, improve speed, consistency and quality of interpretation of screening LDCT scans.
Methods:
A test dataset of baseline Pan-Canadian Early Detection of Lung Cancer Study LDCT scans (New Engl J Med. 2013;369:908-17) was used. This included: 136 scans with lung cancers, 556 scans with benign nodules and 136 scans without nodules. The scans were randomly assigned for analysis by the CV software (CIRRUS Lung Screening, Diagnostic Imaging Analysis Group, Nijmegen, The Netherlands). The annotated scans were then reviewed by a technician without knowledge of the diagnosis. The scans were classified by the technician as either normal (no nodules or benign nodules only, potentially not requiring radiologist review) or abnormal (suspicious of malignancy or other abnormality requiring radiologist review). The results were compared with the Pan-Can Study radiologists. Nodules found by CIRRUS but not by the radiologist were reviewed by a subspecialty trained chest radiologist with 14 years experience in lung cancer screening (JM).
Results:
The overall sensitivity and specificity of the technician to identify an abnormal scan were: 97.7% (95% CI: 96.3 - 98.7) and 98.0% (95% CI: 89.5 - 99.7) respectively. The technician correctly identified all the scans with malignant nodules. The time taken by the technician to read a scan was 208±120 sec.
Conclusion:
A technician assisted by CV software can categorize accurately abnormal scans for review by a radiologist. Pre-screening by a technician and CV software is a promising strategy for reducing workload, improving the speed, consistency and quality of scan interpretation of screening chest CTs. Supported by the Terry Fox Research Institute, The Canadian Partnership Against Cancer and the BC Cancer Foundation on behalf of the Pan-Canadian Early Detection of Lung Cancer Study Group.
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MINI36.06 - Discussant for MINI36.01, MINI36.02, MINI36.03, MINI36.04, MINI36.05 (ID 3443)
18:55 - 19:05 | Author(s): M. Steliga
- Abstract
- Presentation
Abstract not provided
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MINI36.07 - Diagnostic Value of Electromagnetic Navigation Bronchoscopy for Peripheral Pulmonary Lesions : A Randomized Controlled Trial (ID 1152)
19:05 - 19:10 | Author(s): S. Jiayuan, Y. Xin, Z. Xin, B. Han
- Abstract
- Presentation
Background:
Navigational bronchoscope including conventional electromagnetic navigation bronchoscope(ENB) and endobronchial ultrasound(EBUS) with a guide sheath(GS) for transbronchial lung biopsy (TBLB) has improved the diagnostic outcome for peripheral pulmonary lesions (PPLs). However, ENB required the bronchoscope for large diameter of the working channel(>2.6mm) which could limit the deep of the insertion and EBUS-GS could be regarded as the confirmation tool other than navigation system. A new, realtime electromagnetic guidance system for bronchoscopy using a thin bronchoscope(4.0mm) with a GS(1.95mm) for TBLB is a novel method to increase diagnostic yield of PPLs.
Methods:
A prospective, open label, two centers, randomized controlled pilot study involves two diagnostic arms: ENB-GS-TBLB and traditional GS-TBLB which was conducted to determine the ability and safety.ENB-GS-TBLB is performed using an electromagnetic navigation system with a GS and an internal locatable guide with diameter of 1.45 mm. Primary outcome was diagnostic yield. Secondary outcomes were yields by total procedure time, the time for finding lesions and the X-ray time using during operation. Complications were also documented.
Results:
Of the 86 patients recruited, 81 had a definitive histological diagnosis and were included in the final analysis. The diagnostic yield of the ENB-GS-TBLB (87%) was greater than GS-TBLB (64%; p<0.05). The time for finding lesions of the ENB-GS-TBLB(3min 43s) was significantly less than GS-TBLB(4min 44s; p<0.05). ENB-GS-TBLB was independent of lesion size or lobar distribution. No complications were found in both two groups.
Conclusion:
ENB-GS-TBLB seems to be an accurate and safe procedure. It allowed us to improve the diagnostic yield of flexible bronchoscopy in PPLs.
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MINI36.08 - 18F-FDG PET Imaging Utilization in the National Lung Screening Trial (ID 539)
19:10 - 19:15 | Author(s): V.S. Nair, V. Sundaram, M.K. Gould, S.S. Gambhir, M. Desai
- Abstract
Background:
The National Lung Screening Trial (NLST) showed that chest CT screening for patients at risk for lung cancer reduces lung cancer mortality compared to Chest X-Ray (CXR) screening, but with considerable costs due to a high rate of false positive findings. The use of FDG PET has been advocated as a diagnostic tool to aid clinicians in evaluating nodules that may or may not be cancer, but no investigations to date have ascertained current practice patterns in a large group of patients across the U.S.
Methods:
Using data from the NLST, we determined the appropriateness and characteristics of diagnostic FDG PET use in patients with an abnormal finding (defined as a ≥ 4 mm nodule) during lung cancer screening via CT or CXR. Diagnostic FDG PET consisted of either a PET alone or combined PET/CT, which was done prior to a lung cancer diagnosis but after an abnormal finding. Appropriateness was defined as diagnostic FDG PET use for nodules ≥ 8 mm. We used multivariable logistic regression techniques to assess factors associated with diagnostic FDG PET use.
Results:
Of 9,964 patients with an abnormal finding during any of the three rounds of screening, 1,206 (12%) had a diagnostic FDG PET scan at 33 different medical centers across the U.S. (Table 1). Forty percent (n = 484) of these scans were recommended by a radiologist as a follow-up for an abnormal finding. Twenty-seven percent (n = 331) were performed for nodules less than 8 mm, and of these 24% (n = 81) were recommended by radiologists. There were no regional differences in PET use across U.S. areas with endemic fungal disease but patients from the Northeast and Southeast were twice as likely as the West to have a PET scan after a positive screen. Older age, nodule size ≥ 0.8 –2.0 cm, upper lobe location and a spiculated nodule border were associated with increased diagnostic FDG PET use.
Conclusion:
This is the first study to describe differential FDG PET use across the U.S and by medical specialty. Importantly, PET imaging was used inappropriately for small nodule evaluation in one out of four cases. Future studies should characterize associated costs and whether better adherence to current national guidelines can reduce such costs. Figure 1
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- Abstract
- Presentation
Background:
CT-guided cutting needle lung biopsy is important for the diagnosis of lung cancer. The co-axial method is now widely used. However, co-axial method failed to decrease the incidence of pneumothorax. This study is to investigate whether our new-developed “Liquid withdraw” technique (to inject small amount of lidocaine during withdraw of the needle) can reduce incidence of pneumothorax when combined with co-axial technique. Figure 1 Fig.1.What is liquid withdraw
Methods:
From Jan 2013 to Dec 2014, We retrospectively studied 38 CT-guided percutaneous lung biopsy using co-axial and liquid withdraw techniques. The pathologies and complications secondary to biopsy procedure (pneumothorax, bleeding and hemoptysis) were noted. Pneumothorax was graded as mild, moderate, and severe.
Results:
37 cases was diagnosed out of 38 biopsies, of which 23 cases were adenocarcinoma (21 patients consented EGFR mutation test, and 15 cases had EGFR mutaions)，2 squamous cell carcinoma, 1 non-small cell lung cancer (cannot be further classified after IHC), 1 small-cell lung cancer, 2 primary lung cancer of other types, 5 metastatic lung cancer and 3 benign diseases. 4 cases (10.5%) happened pneumothorax (all were mild pneumothorax)，bleeding during biopsy happened in 1 (2.6%) case, 6 cases with a small amount of hemoptysis（15.8%）. No infection, tumor implantation or aeroembolism happened. Figure 1 Fig.2. A case of CT-guided cutting needle lung biopsy using “Liquid Withdarw” technique A: The co-axial inducer needle is located at the margin of the lesion B&C:after biopsy, the lidocaine can be seen in the needle passage and no pnemothorax is found.
Conclusion:
CT-guided percutaneous lung biopsy using co-axial and liquid withdraw is an accurate, safe，reliable technique. Compared to co-axial technique without liquid withdraw, the incidence of pneumothorax was reduced from approximately 35% to 10.5%. More studies according to liquid withdraw technique will be conducted in our future work.
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MINI36.10 - Discussant for MINI36.07, MINI36.08, MINI36.09 (ID 3556)
19:20 - 19:30 | Author(s): D. Grunenwald
- Abstract
- Presentation
Abstract not provided
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MINI36.11 - Pre-Operative Fine Needle Aspiration (FNA) for Diagnosis of Suspected Early Stage Lung Cancer Reduces Non-Malignant Resection Rate (ID 2124)
19:30 - 19:35 | Author(s): J.A. Barta, C.I. Henschke, R. Flores, D.F. Yankelevitz, C.A. Powell
- Abstract
- Presentation
Background:
Rates of resection of non-malignant lung nodules suspected pre-operatively to be lung cancer vary widely and are reported to be as high as 40%. Commonly used modalities in the pre-operative workup of new lung nodules suspicious for lung cancer include positron emission tomography (PET), bronchoscopy, and computed tomography (CT)-guided fine needle aspiration (FNA). We evaluated the non-malignant resection rate (NMRR) and the frequency of benign resections among patients with pre-operative FNA in our lung cancer center.
Methods:
The study population was identified using databases of the Mount Sinai Departments of Thoracic Surgery and Radiology. Eligible patients included those with a CT-guided FNA and/or surgical resection performed during the 12-month period between July 2013 – July 2014 for known or suspected first primary early stage lung cancer presenting with a lung nodule or mass. Cases were included if patients were >18 years of age with no history of cancer treated within 5 years. Patient data were abstracted from the electronic medical records.
Results:
A total of 283 nodules from 264 patients met inclusion criteria. Of these, FNA was performed in 217 (77%) of the 264 patients, with 131 results (60%) categorized as malignant. Similarly, 228 nodules (81%) were PET imaged, and 141 (62%) of these were positive (Standard Uptake Value >2). Sensitivity and specificity of FNA and PET for diagnosis are reported in Table 1. Post-FNA pneumothorax requiring a chest tube occurred in 11/193 FNAs performed at Mount Sinai (6%). Of 208 surgically resected nodules, 27 cases (13.0%) had a non-malignant diagnosis on pathologic examination. The non-malignant resection rate (NMRR) ranged from 0% to 39% by different surgeons and did not correlate with surgical case volume. Among the 142 resections preceded by FNA, 11 (7.7%) were found to have non-malignant pathology. In contrast, among the remaining 66 resections without a pre-operative FNA, 16 (24.2%) were benign (OR 3.81, 95%CI 1.52-9.69; p = 0.001). Figure 1
Conclusion:
In this single center retrospective analysis, the overall NMRR was lower than in previously published reports. Furthermore, the NMRR was significantly lower in thoracic operations preceded by a CT-guided FNA compared with those without a pre-operative FNA. Diagnostic accuracy of FNA in this cohort of patients at moderate to high risk for lung cancer is higher than that of PET, with an acceptably low complication rate. These findings suggest that pre-operative diagnostic confirmation by FNA results in a low rate of non-malignant resection.
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MINI36.12 - Diagnosis of Peripheral Lung Nodules: Cost Analysis of EMB/EBUS Compared to TTNB (ID 254)
19:35 - 19:40 | Author(s): K..A. Lee
- Abstract
- Presentation
Background:
This analysis compares the cost–effectiveness of radial endobronchial ultrasound (EBUS) and electromagnetic navigation (ENB) to transthoracic needle biopsy (TTNB) to achieve diagnosis of suspicious lung lesions. As more centers develop lung screening and lung nodule clinics, there will be a need for diagnosis of small pulmonary nodules. The National Lung Screening Trial (NLST) showed a probable positive Low Dose Computer Tomography (LDCT) incidence of 25%, indicating the number of patients requiring a diagnostic evaluation will increase. The expectation of increased lung cancer screening due to the Centers of Medicare and Medicaid Services approving coverage for LDCT for eligeable patients, and the American College of Chest Physicians (ACCP) recommendation for improved techniques to diagnose peripheral lung lesions necessitate utilizing clinical and economic assessment tools that support clinical decisions. The study seeks to identify the most cost-effective biopsy protocol to reduce costs, and deliver improved diagnostic accuracy.
Methods:
The study reviewed the NLST which enrolled over 50,000 people aged 55–74 years with at least a 30-pack/year smoking history, in fairly good health and non-symptomatic of lung disease. The study found low-dose computed tomography of the chest resulted in a 20% lower mortality from lung cancer compared with those who had chest x-rays. Approximately 25% of the LDCT-screened patients had a positive screen requiring confirmation of the lung lesion. Using an estimate of 5.2 million annual chests CT scans in the USA as a basis for the number of patients seeking a confirmative result before being recommended for surgery for possible benign lung lesions. The cost–effectiveness models employed estimate the direct costs to the hospital and to the patient. Direct costs were calculated using the Medicare Median cost files by Current Procedural Terminology (CPT) code for 2012. Additional costs were added to account for the fee of the procedure room, nursing and clinical support staff, and observation room time. Reimbursement reflects the 2013 Medicare allowable payment exclusive of the geographic adjustment factor. Reimbursement from commercial insurers is constructed upon a conservative multiple of the Medicare allowable. CPT codes subject to the multiple procedure discounts were properly reduced by 50% as they would be for reimbursement purposes for both Medicare and commercial insurance reimbursement.
Results:
Modeling 200 representative patients delegated to; TTNB, bronchoscopy, or R-EBUS-/ENB-enabled endobronchial percutaneous (Endo-Perc) when comparing procedure fees, insurance payment and clinical outcomes, the Endo-Perc technique lead to the most cost-effective option to biopsy the lung lesion. The lower adverse event profile of pneumothorax and reduced cost exhibited by the Endo-Perc procedure; resulted in a benefit of $130,464 compared with a loss of $562,863 for TTNB, or a loss of $103,487 for routine bronchoscopy.
Conclusion:
The results suggest combining R-EBUS with ENB provides a high-diagnostic yield at a lower cost due to the lower risk of a pneumothorax when compared with transthoracic lung biopsy.
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MINI36.13 - Quantitative Computed Tomography as Predictor of Cardiopulmonary Complication after Lobectomy for Lung Cancer in COPD Patients (ID 1227)
19:40 - 19:45 | Author(s): Y. Yasuura, T. Maniwa, N. Miyata, R. Shimizu, H. Kayata, H. Kojima, S. Takahashi, M. Isaka, Y. Ohde
- Abstract
- Presentation
Background:
In lung cancer resection, COPD is a risk factor for postoperative complications. There are few reports about postoperative complications that assume a pictorial emphysematous change an index. We examine a relationship of an emphysematous regional ratio in preoperative CT in patients with COPD who underwent lung cancer resection and cardiopulmonary complication.
Methods:
One hundred fifty-nine patients with COPD who underwent lobectomy for lung cancer in our hospital from 2002 to 2011 were retrospectively evaluated in this study. Preoperative factors, including proportion of emphysematous area measured by CT (percentage of low attenuation area: LAA%), and operative factors were analyzed. Cardiopulmonary complications include pyothorax, pneumonia, atelectasis, acute pulmonary injury, chest tube indwelling, O~2~ long supply and arrythmia.
Results:
Cardiopulmonary complications were observed among 61 patients (38%). Ages, FEV1.0%, LAA% and amounts of blood lost were significantly relevant to cardiopulmonary complications by univariate analysis. Multivariate analysis indicated that patient’s age and LAA% could be significant independent predictors. Table1.Complications incidence by LAA%
Table2. Operative factors in relation to cardiopulmonary complicationsLAA% N complications：n=61 no complications：n=98 p value ～1% 1～10% 10%～ 77 67 15 15(19.5%) 37(55.2%) 9(60.0%) 62(80.5%) 30(44.8%) 6(40.0%) <0.001 variables Odds ratio 95%Confidence Interval p value Age(>70 years) FEV1.0% GOLD PaO2 LAA%（1%～） blood lost（>150ml） 4.612 1.042 2.044 0.973 5.570 2.073 2.028-10.489 0.973-1.117 0.857-4.876 0.940-1.008 2.302-13.480 0.878-4.894 ＜0.001 0.242 0.107 0.128 ＜0.001 0.096
Conclusion:
LAA% is useful for predicting cardiopulmonary complications in patients with COPD undergoing lobectomy for lung cancer.In patients with COPD undergoing lobectomy for lung cancer, 70 years of age or older, the LAA% 1% or more of the cases, more careful intraoperative, and postoperative management are required.
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MINI36.14 - Improving Pathways to Early Lung Cancer Diagnosis: Process Mapping and Qualitative Analysis (ID 746)
19:45 - 19:50 | Author(s): N.M. Rankin, T. Shaw, S. York, D. McGregor, P. Butow, J. Young, K. White, D. Barnes, R. Zielinski, E. Stone
- Abstract
- Presentation
Background:
Lung cancer is one of the most difficult cancers to diagnose in primary care settings. Lung symptomatology alone is a poor indicator of likelihood of diagnosis and in Australia, most primary care practitioners (general practitioners, GPs) will see only one or two lung cancer cases annually. Early diagnosis leads to improved survival with 5-year lung cancer survival much higher in localised disease (30% versus 16% overall). Australia has a mixed public-private model of health services and referral pathways from primary to secondary and tertiary services are based on traditional or informal networks resulting in wide variations in practices. This presentation will report results from diagnostic pathway mapping in lung cancer across three multidisciplinary teams (MDTs) to inform future intervention strategies to reduce variation and improve patient outcomes.
Methods:
We conducted process-mapping workshops with each team to identify the barriers to delivering diagnostic and treatment services. We also developed qualitative interview schedules for GPs and patients. We recruited participants through multiple strategies (mail out, personal invitation from the clinical champion) with local ethics approval.
Results:
Forty-six lung cancer clinicians and four consumers participated in process mapping workshops across three sites. The resulting process maps highlight health system delays and complexities for patients navigating health services, particularly for those living in regional and rural areas. The provision of specialist services for lung cancer diagnosis varies significantly geographically with potential for patients to be lost to follow up. Twelve GPs completed in-depth qualitative interviews or participated in a focus group to identify barriers and enablers in diagnostic pathways. Qualitative analysis reveals that GPs need tailored information about appropriate referrals to specialist pulmonologists or oncologists at the time of a suspicious lung cancer. For GPs without established referral networks, there can be significant uncertainty about the most appropriate referral pathways. Analysis from qualitative interviews with 20 lung cancer patients and their carers indicates that they perceive their GP as having an advocacy role in coordinating their care across specialists’ appointments and diagnostic investigations. Patients reported that personal contact and networking across clinicians in primary, secondary and tertiary settings was a significant factor in the timeliness of investigations or being referred for treatment. In particular, the urgency or severity of symptoms significantly impacted timeliness in securing appointments for investigative diagnostic tests. Patients reported that GPs willing to coordinate their care played an enabling or facilitating role in their care pathway.
Conclusion:
This collaborative project between clinicians and researchers has identified significant barriers and enablers in diagnostic pathways in lung cancer. Primary care practitioners play a significant role in managing patient care and require timely and tailored information about how to refer to a specialist who actively participates in a MDT. We have subsequently developed a protocol to implement a referral decision prompt at the time of CT investigation for those people with a suspicious lung lesion. This prompt will be directed at primary care practitioners and we are currently undertaking a pilot study to examine its feasibility and acceptability.
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MINI36.15 - Discussant for MINI36.11, MINI36.12, MINI36.13, MINI36.14 (ID 3557)
19:50 - 20:00 | Author(s): K. Garg
- Abstract
- Presentation
Abstract not provided
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ORAL 05 - Surgery (ID 97)
- Event: WCLC 2015
- Type: Oral Session
- Track: Treatment of Locoregional Disease – NSCLC
- Presentations: 8
- Moderators:P. Van Schil, F.(. Kong
- Coordinates: 9/07/2015, 10:45 - 12:15, 201+203
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- Abstract
Background:
Identifying surgical non-small cell lung cancer (NSCLC) patients with poor prognosis remains a priority in clinical oncology given their high 5-year mortality. [18]F-FDG PET/CT can add important biological information of glucose metabolism to conventional imaging modality. Pretreatment maximal standard uptake value (SUV~max~), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) may predict prognosis in NSCLC patients. Thus, we performed this meta-analysis to explore the prognostic value of SUV~max~, MTV and TLG on disease-free survival (DFS) and overall survival (OS) in surgical NSCLC patients.
Methods:
A systematic search of MEDLINE, EMBASE and Cochrane Library was performed. Inclusion criteria were: pathologically confirmed NSCLC; [18]F-FDG PET used as an initial imaging tool before treatments; patients underwent curative surgery without neoadjuvant therapy; prospective or retrospective studies reported; complete survival data. Three investigators reviewed and scored each article independently on four dimensions: the scientific design, the generalizability of the results, the analysis of the study data and the PET reports. DFS and OS were considered as the outcome. The correlation of SUV~max~, MTV or TLG with survival was measured by hazard ratio (HR). Sub-group analyses were performed according to the histological subtype and pathological stage. The inter-study heterogeneity was evaluated with the Cochrane’s Q test as well as I[2]. The possibility of publication bias was assessed by visual inspection of a funnel plot and Begg’s test. “Trim and fill” procedure that considers the possibility of hypothetical “missing” studies that might exist was performed to further assess the possible effect of publication bias.
Results:
Thirty studies with 5011 patients were included for the meta-analysis. The mean quality score was 77.5%, ranging from 70.0% to 87.5%. Only one study was prospectively designed. SUV~max~ was measured in 28 studies, all of which were normalized by body weight. MTV was measured in 6 studies and TLG was measured in 5 studies. Adjusted HRs could be determined for 20 studies. For DFS, the combined HRs were 2.61 (95%CI 2.20-3.11, unadjusted) and 3.04 (95%CI 2.24-4.11, adjusted) for SUV~max~, 2.27 (95%CI 1.77-2.90, unadjusted) and 2.49 (95%CI 1.23-5.04, adjusted) for MTV, 2.46 (95%CI 1.91-3.17, unadjusted) and 2.97 (95%CI 1.68-5.28, adjusted) for TLG, respectively. For OS, the pooled HRs were 2.22 (95%CI 1.90–2.61, unadjusted) and 1.61 (95%CI 1.32-1.96, adjusted) for SUV~max~, 3.40 (95%CI 2.27-5.09, unadjusted) and 1.91 (95%CI 1.13-3.22, adjusted) for MTV, and 3.85 (95%CI 2.52-5.86, unadjusted) and 1.76 (95%CI 0.96-3.21, adjusted) for TLG, respectively. When the publication bias was detected by Begg’s test, “trim and fill” procedure was performed and similar HRs were obtained. The predictive role of SUV~max~, MTV and TLG remained similar in the sub-group analysis.
Conclusion:
High values of SUV~max~, MTV and TLG predicted a higher risk of disease recurrence or death in patients with surgical NSCLC. It is suggested that FDG PET/CT be used to select patients at high risk of disease recurrence or death and may benefit from more aggressive treatments. Further individual patient data should be analyzed to determine the optimal threshold value.
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ORAL05.02 - Quality of Resection in Pathological N2 NSCLC in the Phase 3 Lung Adjuvant Radiotherapy Trial (Lung ART): An Important Factor (ID 1001)
11:16 - 11:27 | Author(s): P. Thomas, J. Edwards, P. Van Schil, R. Rami-Porta, G. Goma, A. Dunant, C. Le Pechoux
- Abstract
- Presentation
Background:
The main objective of the ongoing phase III Lung Adjuvant Radiotherapy Trial (Lung ART) is to study the impact of post-operative conformal radiotherapy (PORT) on disease-free survival (DFS) in a population of patients with completely resected pathologically proven N2 non-small cell lung cancer (NSCLC), with or without induction or adjuvant chemotherapy. Quality of surgical resection and extent of lymph node dissection are critically important in the interpretation of results.
Methods:
A surgical advisory committee composed of 4 international expert thoracic surgeons meets regularly in order to establish the quality of resection, taking into consideration the International Association for the Study of Lung Cancer and European Society of Thoracic Surgeons published guidelines. The committee reviews anonymized surgical and pathological reports, and establishes whether tumor resection can be considered complete (no residual tumor and adequate lymph node assessment), uncertain (highest mediastinal nodal station involved, incomplete nodal exploration, involved N2 removed in fragments) or incomplete (presence of residual tumor). Nodal exploration is evaluated according to recommendations and classified as sampling, selective dissection or extensive dissection.
Results:
As of April 15th 2015, 298 patients have been included in the Lung ART trial and 116 patients’ reports have been analyzed by the surgical advisory committee. The basic characteristics are specified in the following table:
Nodal dissection was performed according to lobar location specific recommendations in most patients: for instance, station 7 was explored in 91% patients and right inferior paratracheal station 4R in 93% of right side tumours. Nodal dissection was performed according to recommendations in 71% pts; 16% patients had sampling, 22% a selective dissection and 62% a systematic dissection. Resection was considered complete (R0) in 43%, uncertain in 42%, microscopically incomplete (R1) in 14% and macroscopically incomplete (R2) in 1 patient. The most frequent reason for “uncertain resection” was involvement of the highest mediastinal lymph node.Total n=116 Frequency Percent Induction chemotherapy no 89 77% yes 27 23% Type of surgery for right-side tumors 70 60% lobectomy 49 70% bilobectomy 9 13% pneumonectomy 5 7% other 7 10% for left-side tumors 46 40% lobectomy 34 74% pneumonectomy 10 22% other 2 4% Tumor Size (mm) Median size (range) 35 [0*-105] Number of mediastinal lymph nodes examined Median number (range) 10 [1-37] Number of mediastinal lymph nodes involved Median number (range) 1[0*-15] Number of mediastinal nodal stations involved 0* 5 4% 1 79 68% 2 20 17% >2 12 11% * patients with downstaging after induction chemotherapy
Conclusion:
Most adjuvant trials have included completely resected patients, without monitoring of the quality of nodal exploration and resection. This analysis outlines the importance of an external committee evaluating the quality of resection in stage IIIA-N2 NSCLC, and the findings of this audit will be useful in the interpretation of the results of the trial.
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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, M. Fishbein, W..D. Wallace, G. Hoal, M. Doyle, L. Hua-Feng, J. Benfield
- 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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ORAL05.04 - Discussant for ORAL05.01, ORAL05.02, ORAL05.03 (ID 3294)
11:38 - 11:48 | Author(s): I. Opitz
- Abstract
- Presentation
Abstract not provided
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ORAL05.05 - Trimodality Therapy in the Treatment of Stage IIIA Non-Small Cell Lung Cancer (NSCLC): A National Cancer Database Analysis (ID 2962)
11:48 - 11:59 | Author(s): M. Behera, C. Steuer, F. Fernandez, Y. Liu, C. Fu, T.W. Gillespie, K.A. Higgins, N. Saba, R.N. Pillai, S. Force, S. Pakkala, D. Shin, T.K. Owonikoko, C.P. Belani, W.J. Curran, F. Khuri, S.S. Ramalingam
- Abstract
Background:
Significant controversy remains regarding the care of patients (pts) with clinical stage IIIA NSCLC. While multi-modality therapy is an acceptable strategy in selected pts, the optimal approach is not firmly established. We analyzed outcomes and predictors associated with trimodality therapy (TT) in the National Cancer Database (NCDB), an oncology outcomes database administered by the American College of Surgeons and the American Cancer Society.
Methods:
The NCDB was queried from 2003-2011 for NSCLC pts diagnosed with stage IIIA-N2 disease and treated with chemotherapy and radiation (CRT). Data was extracted on patient demographics, tumor pathology, treatments and outcomes. Three cohorts of pts were studied - CRT only/no surgery (NS), CRT + lobectomy (L) and CRT + pneumonectomy(P). The univariate and multivariable analyses (MV) were conducted using Cox proportional hazards model and log rank tests. All analyses were performed using SAS Version 9.3.
Results:
A total of 29,584 pts were included in this analysis: NS-91.7%, L-7%, and P-1.5%. Pt characteristics: median age 66 years (yrs); males 56%; whites 86%; academic centers 27%; metro locations 78%; government insured 63%; Charlson/Deyo comorbidity score 0 in 66%. Pts < 60 yrs were more likely to receive TT- L (47%), P (60%) vs. NS (29%); p<0.001. Pts in academic centers were more likely to get TT than NS (42% vs. 25%). On MV analysis, L and P had significantly better survival vs. NS: HR 0.43 (0.38-0.48) and HR 0.57 (0.46-0.71) respectively; p <0.001. The median survival of L, P and NS were 44.5 m vs. 25.6 m vs. 15.7 m (p<0.001) and 5- year survival rates (SR) were 44% vs. 33% vs. 14% respectively. 30-day mortality was higher in P vs. L [7% vs. 2.6%; OR 0.26(0.16-0.45); p<0.001]. Pts with <2 lymph nodes (LN) had better survival than pts with >2 LNs in L (50% vs. 37%; 60m vs. 38.8m) but worse in NS (13.8% vs.16.4%; 15.3m vs.18.5m). On MV analysis of LNs, L had better survival than NS: HR 0.4 (0.35-0.46) in <2 LN pts and HR 0.56 (0.46-0.69) in ≥2 LN pts; p<0.001. In pts with <2 LN, L had better survival than P (60m vs. 25.5m; p<0.0001). L and P had better SR than NS in all ages: 48% vs.37% vs. 19% in ≤60 yrs; 42% vs. 30% vs.14% in 61-70 yrs, 36% vs.19% vs. 10% in >70 yrs.
Conclusion:
TT was utilized in less than 10% of pts with stage IIIA-N2 disease, suggesting high degree of pt selection. In this selected group, TT was associated with favorable outcomes relative to CRT alone.
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- Abstract
- Presentation
Background:
Video-assisted thoracoscopic lobectomy(VATS) is preferred over thoracotomy for the treatment of early stage non-small cell lung cancer (NSCLC). However, little evidenceindicated its perioperative and oncologic outcomes for advanced-stage NSCLC and the result of VATS surgery may be overestimated since the majority of patients were stage I patients in previous studies. Therefore, we evaluate whether VATS lobectomy for locally advanced NSCLC could be performed safely and with acceptable short- and long-term outcomes when compared with standard thoracotomy on a well-balanced population from a multi-institutional database.
Methods:
Tumors that are greater than 5 cm in diameter, T3 or T4 tumors, tumors after neo-adjuvant treatment, and/or tumors with lymph node metastasis are defined to be locally advanced. By using a multi-institutional prospective database of high level comprehensive cancer hospitals, we analyzed locally advanced NSCLC patients who underwent lobectomy. VATS lobectomies were all performed by an improved technique, which had achieved proficiency that has been published previously. Using propensity-matched analysis based on preoperative variables, perioperative outcomes, oncologic efficacy and long-term survival were compared between VATS lobectomy and thoracotomy.
Results:
Matching based on propensity scores produced 125 patients in each group. Patient and tumor characteristics were similar. Conversion rate from VATS to thoracotomy is 9.6%. There were no intraoperative deaths and 1 perioperative death in each group. Postoperative outcomes like median operative time, blood loss and tube duration were similar between VATS and thoracotomy, Hospital length of stay was shorter after VATS than thoracotomy(10.4d vs 11.4d, p<0.01). VATS group had significant lower level of postoperative pain than thoracotomy group (p<0.01). The overall incidence of postoperative complications was 28.8% (36/125) and 36.0% (45/125)in the VATS group and in the thoracotomy group, respectively(p = 0.14).Similar number of lymph nodes (16.2vs 14.8, p= 0.148)and nodal stations (5.72 vs 5.66, p= 0.781) were removed by VATS and thoracotomy. Similar proportion of patients accepted postoperative chemotherapy (73.6% vs 72.0%, p= 0.776) , and completed similar cycles of postoperative chemotherapy (2.47 vs.2.35, p = 0.602) in the two groups. Median follow-up was 36.6 months. There were no significant differences in locoregional and distant recurrence patterns between the two groups. Disease-free survival(DFS) at 3-years were 50.1% and 47.3%, 5- years were 40.0% and 37.0% in the VATS and thoracotomy groups, respectively (p=0.878). Overall survival(OS) at 3-years were 75.0% and 68.9%, 5-years were 42.2% and 43.1% in the VATS and thoracotomy groups, respectively (p =0.551). Multivariate Cox regression analyses of DFS and OS confirmed the noninferiority of VATS, and showed that significant predictors of worse DFS and OS were advanced pathologic stage (HR,2.235; 95% CI,1.564 to 3.193; p<0.001), and without postoperative chemotherapy (HR,1.594; 95% CI,1.095 to 2.321; p=0.015).
Conclusion:
VATS lobectomy for locally advanced stage NSCLC can be performed safely, with shorter length of hospital stay, lower level of pain and showed similar long-term survivals compared to thoracotomy. With continued experience and optimized technique, VATS lobectomy can be performed in majority of cases without compromising the perioperative outcomes and oncologic efficacy. This work was supported by a funding named‘Beijing Municipal Science and Technology Project (D141100000214004)
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- Abstract
- Presentation
Background:
Individual academic societies have published different recommendations about definitions and requirement of nodal assessment. It's generally agreed that radical mediastinal lymphadenectomy will provide accurate information for pathological staging and guiding adjuvant therapy. However it is not clearly established whether mediastinal lymphadenectomy compliant with international criteria will improve the oncological outcomes of clinical early-stage lung cancer. This retrospective study was aimed to compare the long-term survival between the cases treated with lymphadenectomy fulfilling the NCCN criteria and other cases not met the criteria in clinical early-stage lung cancer patients.
Methods:
During the investigation period, 712 consecutive cases of clinical N0/1 entered the analysis, confirming as 152 cases of pN2 (pathological N2) and 560 of pN0-1 (pathological N0-1) disease after surgery. Group A was defined as the cases fulfilling the National Comprehensive Cancer Network (NCCN) lymphadenectomy criteria (≥three stations of N2 nodes dissection) and Group B was those who did not meet the criteria. Two groups were stratified by pN status and the outcomes were analyzed and multivariate Cox regression was performed to determine prognostic factors.
Results:
5-year Overall survival (OS) and 5-year disease-free survival (DFS) were significantly different between two groups at cN0/1-pN2 status (5-year OS rates, 50±5% vs. 25±9%, p=0.006; 5-year DFS rates, 31.0±4% vs. 13±7%, p=0.014), but not at pN0-1 status (Figure 1). T staging and lymphadenectomy fulfilling NCCN criteria were prognostic factors in cN0/1-pN2 group by multivariate regression analysis. Furthermore, the cases treated with ≥ 4 stations of mediastinal lymph nodes dissection could not achieve better survival benefit compared to those harvesting 3 stations of N2 node in cN0/1-pN2 group (the 5-year OS rates, 46±6% vs. 59±9%, p=0.152).The spreading pattern of mediastinal nodes among pN2 cases was featured by tumor location. The most frequent involved station for right upper lobe-located lung cancer was 4R (83.7%), followed by 7 (37%) and 2R (14.0%). The top 3 involved stations for other cancer locations were 7 (75%), 4R (25%) and 2R (6.3%) for right middle lobe; 7 (81.6%), 4R (34.2%) and 2R (10.5%) for right lower lobe; 5+6 (90.9%), 4L (22.7%) and 7 (4.5%) for left upper lobe; 7 (66.7%), 5+6 (42.4%) and 8 (9.1%) for left lower lobe. Figure 1
Conclusion:
Mediastinal lymphadenectomy fulfilling with NCCN criteria may only improve the survival of pathological upstaging subgroup (cN0/1-pN2) among patients with clinical early-stage lung cancer. More extended dissection of mediastinal lymph node (≥ 4 stations) may not further improve the outcome in this group.
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ORAL05.08 - Discussant for ORAL05.05, ORAL05.06, ORAL05.07 (ID 3295)
12:21 - 12:31 | Author(s): E. Ruffini
- Abstract
- Presentation
Abstract not provided
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Author of
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MINI 04 - Clinical Care of Lung Cancer (ID 102)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:L. Gaspar, V. Westeel
- Coordinates: 9/07/2015, 16:45 - 18:15, Mile High Ballroom 2c-3c
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MINI04.06 - During-Treatment PET Metabolic Tumor Volume (MTV) Instead of FDG Activity Is Predictive of Survival in Patients with Non-Small Cell Lung Cancer (ID 3174)
17:15 - 17:20 | Author(s): F.(. Kong
- Abstract
- Presentation
Background:
We have previously reported that tumor reduces in activity and volume during the course of radiotherapy (RT), and such changes were correlated with post-treatment “tumor response”, known as a significant factor for overall survival in patients with non-small cell lung cancer (NSCLC). This study aimed to determine whether the metabolic activity or metabolic tumor volume (MTV) obtained from the during-treatment FDG-PET is predictive of overall survival in NSCLC.
Methods:
Patients with stage I-III NSCLC enrolled in prospective studies with during-treatment FDG-PET were eligible for this study. All patients were treated with a definitive course of RT + chemotherapy. FDG-PET/CT scans were acquired within 2 weeks before RT (pre-RT) and at about two thirds of the total dose delivered (during-RT). PET-MTVs were delineated by a tumor/aorta ratio of 1.5 autosegmentation combined with manual editing based on CT anatomy, as previously described (Mahasittiwat et al, 2013). FDG-activity was measured as maximum standard update value (SUVmax) and the average activity (SUVmean) of the defined MTV. Total lesion glycolysis (TLG) was computed as the product of MTV and SUVmean. CT gross tumor volume (CT-GTV) were also delineated in a consistent manner. Data are presented as mean (95% confident interval). P<0.05 is considered to be statistically significant.
Results:
A total of 129 patients with a minimum follow-up of 24 months (for surviving patients) were included in this study. The majority of subjects were male (73%), white (96%), current or former smokers (87%) with an average age of 67 years (range 45-92). Seventy-nine percent were treated with chemotherapy in combination with RT (dose range 45-90 Gy). Of the pre-RT PET parameters, neither SUVmax nor SUVmean was significant, while CT-GTV (P=0.03), PET-MTV (p=0.008), and PET-TLG (p=0.005) were all significant for overall survival. After 2/3 treatments were delivered, the mean SUVmax, SUVmean, CT-GTV, PET-MTV, and PET-TLG all decreased significantly (P<0.001) and remarkably (more than 30% reduction), with the PET-MTV showing the greatest extent of reduction. During-RT SUVmax or SUVmean were not significantly associated with overall survival, either as continuous variables or as binominal variables (split from median). While during-RT CT-GTV was a significant factor for survival (P=0.04), yet during-RT PET-MTV and PET-TLG as continuous variables were not. However, patients with during-RT PET-MTV values greater than the median had significantly shorter median survival (21 months, 95%CI: 12.1-32.0) than those of below the median (38 months, 95%CI: 29.0-89.9, p=0.01). The absolute reductions in SUVmax or SUVmean or CT-GTV were not, but changes of PET-MTV and PET-TLG during-RT were significantly associated with overall survival. Smaller reductions from Pre-RT to during-RT were associated with an increased risk of death for PET-MTV (HR=1.003, 95%CI: 1.001–1.006, P=0.01) and PET-TLG (HR=1.001, 95%CI: 1.000–1.001, P=0.02), respectively.
Conclusion:
MTV instead of SUV during the course of RT are significantly associated with overall survival in patients with NSCLC. Larger MTV during-RT may lead to worse survival. RTOG1106/ACRIN6697 is ongoing to adapt radiation therapy plan to give higher dose to residual PET-MTV during-RT to improve tumor control and overall survival.
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P1.02 - Poster Session/ Treatment of Localized Disease – NSCLC (ID 209)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Localized Disease - NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P1.02-037 - Thoracic Radiation-Induced Pleural Effusion and Risk Factors in Patients with Lung Cancer (ID 1397)
09:30 - 09:30 | Author(s): F.(. Kong
- Abstract
Background:
Pleural effusion is regarded as a frequent late toxicity after thoracic radiotherapy (TRT). However, recent literature is lacking on this toxicity. This study aimed to examine the patient and dosimetric risk factors associated with radiation induced pleural effusion (RIPE) in lung cancer patients treated with TRT.
Methods:
Lung cancer patients treated with TRT having follow-up imaging, CT or PET/CT, were eligible. Pleural effusion of increased volume after TRT without evidence of tumor progression was considered to be RIPE. Parameters of lung dose-volume histogram including percent volumes irradiated with 5 to 55 Gy (V5-V55) and mean lung dose (MLD) were analyzed. Optimal dosimetric thresholds for RIPE were calculated by receiver operating characteristic (ROC) analysis. Associating clinical and treatment-related risk factors for RIPE were detected by univariate and multivariate analyses with SPSS 18.0. Data were considered statistically significant at value of p < 0.05.
Results:
Of 806 consecutive patients who received TRT at two institutions, 205 had post-treatment imaging available and were included in this study. The median (range) age was 63 (34-85) years; Male, Caucasian race, current smokers, stage III and squamous cell cancer accounted for 73.2%, 81.0%, 50.7%, 66.8% and 27.8%, respectively. The median follow-up duration was 14.6 (range, 0.7-80.8) months. Of 51 patients (24.9%) who developed RIPE, 40 had symptomatic RIPE including chest pain (47.1%), cough (23.5%) and short of breath or dyspnea (35.3%). The median (range) RIPE interval from end of TRT was 3.7 (0.6-18.0) months. The RIPE rates of the two institutions were 20.2% and 32.1% with a borderline significance (p = 0.053). Caucasian race (HR = 2.930, 95% CI: 1.197-7.172, p = 0.019) and histology of squamous cell lung cancer (HR = 0.645, 95% CI: 0.425-0.980, p = 0.04) were significantly associated with the low risk of RIPE, while age (p = 0.378), gender (p = 0.071), stage (p = 0.148), radiation dose (p = 0.782) and concurrent chemotherapy (p = 0.173) were not. The whole lung V5, V10, V15, V20, V25, V30, V35, V40, V45, V50 and MLD were significantly higher in patients with RIPE than in those without RIPE (p = 0.007, 0.022, 0.044, 0.048, 0.034, 0.016, 0.010, 0.026, 0.040 and 0.014), and only V5 was the significant predictive factor for both RIPE and symptomatic RIPE (p = 0.007 and 0.021) with the largest areas under ROC curve (AUC = 0.779). Using a cutpoint of 41.5% for V5, the sensitivity and specificity were 100% and 61.5%, respectively.
Conclusion:
Radiation induced pleural effusion is notable. Caucasian race and squamous cell tumor histology may be associated with lower risk of RIPE. The whole lung V5 seems to be a significant risk factor for symptomatic RIPE.
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P2.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 234)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P2.04-090 - Changes in Circulating Epidermal Growth Factor Receptor (EGFR) during Radiotherapy in Non-Small Cell Lung Cancer (NSCLC) Patients (ID 2436)
09:30 - 09:30 | Author(s): F.(. Kong
- Abstract
Background:
Epidermal growth factor receptor (EGFR) is overexpressed in a variety of malignant tumors including lung cancer. A circulating isoform of EGFR has been detected in the blood of lung cancer patients. Previous reports suggest that low baseline plasma EGFR concentrations are associated with reduced survival in patients with stage IV non-small cell lung cancer (NSCLC) post-chemotherapy. The goal of the present study was to determine whether: 1) plasma EGFR concentrations change during- and/or after radiotherapy, 2) the changes are associated with overall survival (OS) in stage I-III NSCLC following radiation treatment.
Methods:
Patients enrolled in prospective studies in which platelet poor plasma samples had been collected were eligible. All patients received radiation-based treatment. Patient age, gender, ECOG score, clinical stage, pathology, smoking history, chemotherapy and radiotherapy were all included in this analysis. Blood samples were collected pre-radiotherapy (pre-), during radiotherapy (2 weeks) (2w), during radiotherapy (4 weeks) (4w) and post-radiotherapy (more than 4 weeks post-radiotherapy). Plasma EGFR concentrations were measured using a commercial enzyme-linked immunoassay kit (BosterBio Inc., Pleasanton, CA) that detects the extracellular domain of EGFR. The primary endpoint was OS.
Results:
183 patients with median age of 66, 143 male and 40 female, were included in this study. The median OS was 15.5 months (95% confidence interval [CI]: 20.8-27.3). The mean plasma concentration of EGFR was 35.6 ng/ml for pre- (n=116, 95% CI: 33.9-37.4); 22.4 ng/ml for 2w (n=114, 95% CI: 20.8-24.0); 34.5 ng/ml for 4w (n=114, 95% CI: 31.4-37.7); and 45.0 ng/ml for post (n=114, 95% CI: 40.1-49.9). The plasma level at 2w was significantly lower than pre-levels (p < 0.01). The plasma EGFR level at 4w was significantly higher than at 2w (p < 0.01), though it was not significantly different from that of pre-RT levels. There is a significant increase in EGFR levels in post-RT treated patients (p < 0.01). Post-treatment levels are above all other points observed in cancer patients, including at baseline and during-RT. However, no significant correlation between the levels of EGFR and OS, or between the ratio 2w/pre or post/pre and OS were observed. Kaplan-Meier survival analysis showed pre- EGFR concentrations [22.2 months (95% CI: 6.8-37.7) versus 23.5 months (95% CI: 14.1-32.9) (p = 0.527)] and fold changes of 2w/pre- [24.5 months (95% CI: 11.2-35.9) versus 23.7 months (95% CI: 12.2-42.3) (p=0.928)] respectively.
Conclusion:
In parallel with previous reports for the treatment of NSCLC patients with gefitinib, RT results in a decrease in EGFR plasma concentrations shortly after therapy (2 weeks), but an increase relative to baseline levels by 4 weeks, followed by a further increase (to above baseline levels) by 3 months post-treatment. In patients treated with gefitinib, this increase correlated with worse response to therapy. Here there does not appear to be a correlation between increased plasma EGFR levels and OS following RT. The biologic mechanism(s) underlying these observations, and their clinical implications warrant further study.
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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: 2
- Moderators:
- Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P3.04-067 - Inflammatory Cytokines Are Associated with the Development of Fatigue in Patients with NSCLC Treated with Definitive Radiotherapy (ID 2821)
09:30 - 09:30 | Author(s): F.(. Kong
- Abstract
Background:
Fatigue is one of the most common symptoms in cancer patients at baseline and or treatment which affects cancer patients’ quality of life. This study is to evaluate the association of inflammatory cytokines with the development of fatigue in patients with NSCLC treated with definitive radiation therapy (RT).
Methods:
109 patients with stage I-IIINSCLC and ECOG 0-2 treated with definitive RT from prospective studies were included. The median age was 66 years (range 43-85), and 84 patients (77.1%) had stage IIIdisease. The median RT dose was 70 Gy (range 34-87.9) at 1.8~2.9 Gy/fx for 103 patients and 6 (5.5%) received stereotactic body RT (SBRT) to a total dose of 50-55Gy at 10-11 Gy/fx. Seventy-six (69.7%) received concurrent and 31 (28.4%) consolidated chemotherapy. Thirty inflammatory, pro-inflammatory, immunomodulation cytokines were measured in plasma samples before RT, using ELISA. Fatigue was evaluated and scored according to CTCAE 3.0 before, 2, 4, 6 weeks during- and 3, 6, 9, 12, 18, 24 months after RT. The fatigue scores from all time points are averaged for each person to create a composite score, which is the endpoint of this analysis. Spearman's rho test was used to check the association of cytokine levels and other clinical factors with fatigue. The p-value of the cytokines are adjusted using the Benjamini-Hochberg procedure.
Results:
109 patients had fatigue information available before, 2, 4 and 6 weeks during RT, and 106, 101, 98, 97, 92 and 88 had fatigue information available at 3, 6, 9, 12, 18, 24 months after RT, respectively. The incidence of grade 1-3 fatigue was 37.6% before RT, 52.3%, 60.6%, 65.1% at 2, 4, 6 weeks during RT, and 62.3%, 50.5%, 33.7%, 28.9%, 14.1%, 13.6% at 3, 6, 9, 12, 18, 24 months after RT, respectively. Grade 3 fatigue was rare, less than 1% and no grade 4-5 fatigue occurred. Among 30 cytokines, IL-10 (p=0.019) and IP-10 (p=0.054) were significantly associated with fatigue. Lower level of IL-10 and higher level of IP-10 were associated with less fatigue score. SBRT (p=0.002), and consolidated chemotherapy (p=0.049) were significantly associated with fatigue. Patients treated with SBRT had lower fatigue score, but those with consolidated chemotherapy had higher fatigue score. IL-10 was not related with the use of SBRT (p=0.26) or consolidated chemotherapy (p=0.11). IP-10 was not related with the use of consolidated chemotherapy (p=0.76), but it is significantly related with the use of SBRT (p=0.01) and SBRT individuals had higher IP-10 levels. By excluding the 6 SBRT patients, IP-10 was significantly associated with fatigue for non-SBRT patients (p=0.02). Age (p=0.09), gender (p=0.59), histology (p=0.56), ECOG (p=0.16), weight loss (p=0.85), COPD (p=0.16), smoking (p=0.99), stage (p=0.89), biological equivalent RT dose for non-SBRT patients (p=0.12), and concurrent chemotherapy (p=0.59), were not associated with fatigue.
Conclusion:
For patients with NSCLC treated with definitive RT, fatigue increases during RT and decreases over time after completion of RT, with peak severity at 6 weeks during RT. Plasma level of IL-10 and IP-10 before RT, SBRT and consolidated chemotherapy play important roles in the development of fatigue.
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P3.04-104 - Radiation Pneumonitis: Assessment by Inflammation Imaging with Tc-99m HMPAO - Clinical Trial in Progress (ID 2790)
09:30 - 09:30 | Author(s): F.(. Kong
- Abstract
Background:
Background: Over 60% of patients with non-small-cell lung carcinoma (NSCLC) require radiation treatment, with an overall cure rate < 10-15% and moderate toxicity in 10-30% of treated patients. While high-dose radiation improves survival, concern over radiation-induced toxicities including radiation pneumonitis (RP) have limited its use. Predicting probability of tumor control and lung toxicity offers a promising strategy for individualized radiation therapy (RT), such as giving higher dose radiation to resistant tumors when probability of toxicity is low, improving the therapeutic ratio. Technetium-99m (Tc-99m) hexamethylpropylene amine oxime (HMPAO) imaging is an established method for evaluation of brain perfusion, tissue inflammation, infection, and abscess localization. Tc-99m HMPAO, a lipophilic biogenic amine that easily crosses the cell membrane into the endothelial cytoplasm, is a sensitive indicator of endothelial cell damage and microvascular injury, penetrating into the alveolar macrophage reflecting impaired alveolar integrity proportional to inflammation and lung toxicity. Once intracellular, it is retained by conversion to hydrophilic nondiffusable form mediated by glutathione oxidation/reduction within the epithelial lining and bronchoalveolar cell, and has been used for non-invasive detection of lung injury proportional to severity. We used Tc-99m HMPAO scintigraphy to semiquantitatively document the presence and severity of lung toxicity in 4 patients undergoing RT for NSCLC.
Methods:
Methods: Four patients with NSCLC (3 Stage IIIB receiving concurrent RT and carboplatin/paclitaxel chemotherapy, 1 Stage IB RT alone) underwent lung computed tomography (CT), positron emission tomography (PET)/CT with 2-deoxy-2-[fluorine-18]fluoro-D-glucose (FDG), ventilation (V)/perfusion (Q) lung imaging with Tc-99m diethylene triamine pentaacetic acid/Tc-99m macroaggregated albumin, and inflammation imaging with Tc-99m HMPAO; at baseline prior to treatment, during RT after 36-50 Gray, and at 3 months following radiation completion.
Results:
Results: All patients had matching V/Q lung abnormalities in the areas of tumor and RT, and tumor-positive baseline FDG PET/CT imaging that showed response to therapy. Three patients without RP had HMPAO imaging that mimicked Q lung imaging on all 3 sequential imaging studies. No patient experienced RP during RT, while one patient experienced grade 1 RP at 3 months, showing progressive increase in HMPAO inflammatory uptake in adjacent lung from baseline to during-RT to 3 months post-RT imaging, not appreciated on FDG PET/CT imaging (Figure 1).
Conclusion:
Conclusion: Tc-99m HMPAO nuclear imaging may provide more sensitive evaluation of the presence and severity of RP. In this case, uptake on during-RT imaging predated, predicted, and confirmed development of grade 1 RP at 3 months. Figure 1
