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H. Ohmatsu
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MINI 36 - Imaging and Diagnostic Workup (ID 163)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Screening and Early Detection
- Presentations: 1
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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): H. Ohmatsu
- 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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ORAL 24 - CT Detected Nodules - Predicting Biological Outcome (ID 122)
- Event: WCLC 2015
- Type: Oral Session
- Track: Screening and Early Detection
- Presentations: 1
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ORAL24.01 - Natural History of Pulmonary Subsolid Nodules: A Prospective Multicenter Study (ID 1245)
10:45 - 10:56 | Author(s): H. Ohmatsu
- Abstract
- Presentation
Background:
The purpose of this prospective multicenter study was to evaluate the natural course of progression of pulmonary subsolid nodules.
Methods:
Eight facilities participated in this prospective study. This study was conducted with the approval of the institutional review board of each of the participating institutions. Written informed consent was obtained from all the patients. A total of 845 patients with 1325 pulmonary subsolid nodules were registered, of whom 795 patients (341 men, 454 women; mean age, 62 years [range, 31-88]) with 1238 subsolid nodules were selected as being eligible for this study. In this study, the pulmonary subsolid nodules were classified into three categories: pure ground-glass nodules (hereafter abbreviated as PGGNs), heterogeneous GGNs (solid component detected only in the lung window setting; hereafter abbreviated as HGGN), and part-solid nodules (solid component also detected in the mediastinal window setting). The CT images of the nodules that showed progression were reviewed by an expert radiologists’ panel. Pathological specimens of the resected nodules were reviewed by an expert pathologists’ panel.
Results:
The mean prospective follow-up period was 4.3 ± 2.5 years (range, 0.2–12.1; median, 3.5 [IQR, 2.4–6.0]). After exclusion of 9 resected nodules (2 no-lung-cancer nodules and 7 lung cancers not reviewed by the expert pathologists’ panel), the pulmonary subsolid nodules were classified as follows at the baseline: 1046 PGGNs, 81 HGGNs, and 102 part-solid nodules. Among the 1047 PGGNs, 13 (13/1046; 1.2%) developed into HGGNs, and 56 (56/1046; 5.4%) developed into part-solid nodules. Among the 81 HGGNs, 16 (16/81; 19.8%) developed into part-solid nodules. Thus, the subsolid nodules were classified as follows at the time of the final follow-up: 977 PGGNs, 78 HGGNs and 174 part-solid nodules. Of the 977 PGGNs, 35 (3.6%) were resected; from the histopathologic standpoint, the 35 resected PGGNs consisted of 9 minimally invasive adenocarcinomas (MIAs), 21 adenocarcinomas in situ (AISs), and 5 atypical adenomatous hyperplasias (AAHs). Of the 78 HGGNs, 7 (9%) were resected; from the histopathologic standpoint, the 7 HGGNs consisted of 5 MIAs and 2 AISs. Of the 174 part-solid nodules, 49 (28.2%) were resected; from the histopathologic standpoint, the 49 part-solid nodules consisted of 12 invasive adenocarcinomas, 26 MIAs, 10 AISs, and 1 AAHs. In total, 12 (12/1229, 1%) invasive adenocarcinomas, 40 (40/1229; 3.3%) MIAs, 33 (33/1229; 2.7%) AISs, and 6 (6/1229; 0.5%) AAHs were resected as of December 31, 2013; For the PGGNs, the mean period to development into part-solid nodules was 3.8 ± 2.0 years (range, 0.5-8.7; median, 3.4 [IQR, 2.0–5.2]); for the HGGNs, the mean period to development into part-solid nodules was 2.1 ± 2.3 years (range, 0.2–8.8; median, 1.0 [IQR, 0.7–3.4]) (P=0.0004).
Conclusion:
Our prospective multicenter study revealed the frequency and period of development from PGGNs and HGGNs into part-solid nodules. Invasive adenocarcinomas were only diagnosed in the part-solid nodules. The findings of the study may contribute to the development of guidelines for follow-up of pulmonary subsolid nodules.
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P1.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 206)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P1.01-022 - Radiologic Features of Advanced ALK-Rearranged Lung Cancer (ID 995)
09:30 - 09:30 | Author(s): H. Ohmatsu
- Abstract
Background:
Reportedly, the radiologic features of most primary resectable lung cancers harboring an anaplastic lymphoma kinase (ALK)-fusion do not exhibit a ground-glass opacity (GGO) component when viewed using CT. However, little is known about the features of advanced ALK-rearranged lung cancer.
Methods:
The radiologic features of 21 advanced ALK-positive lung cancers treated at the National Cancer Center Hospital East between January 2012 and June 2014 were retrospectively investigated. ALK-fusion was confirmed using IHC and FISH or RT-PCR methods. The primary tumor’s diameter and characteristics (i.e., presence of a GGO component, notch, spiculation, and pleural indentation) as viewed using CT and the SUVmax observed using PET before treatment were evaluated. The radiologic features of 181 EGFR/ALK-negative non-sq NSCLCs treated during the same period were also evaluated as a control group. In addition, sites of distant metastases were evaluated.
Results:
The median age of patients with ALK-positive lung cancer was 58 years (range, 25-83 years). Of the 21 patients, 8 (39%) were female and 11 (52%) were never-smokers. The proportion of primary tumors smaller than 3 cm was significantly higher among the ALK-positive tumors than among the EGFR/ALK-negative tumors (48% vs. 21%, P = 0.01). Notches (71% vs. 41%, P = 0.01) and pleural indentations (81% vs. 55%, P = 0.03) were significantly more common among the ALK-positive tumors than among the EGFR/ALK-negative tumors. No significant differences in peripheral GGO (4.8% vs. 6.1%, P = 1.00) and spiculation (71.4% vs. 54.7%, P = 0.17) were observed. The median SUVmax values of the primary tumors were not significantly different (9.33 [range 4.56-28.81] vs. 10.54 [range 1.20-38.18], P = 0.91). Regarding the sites of distant metastases, liver (33% vs. 8%, P < 0.03) and pleural dissemination (48% vs. 24%, P = 0.03) were more frequent among patients with ALK-positive tumors than among patients with EGFR/ALK-negative tumors.
Conclusion:
We identified the radiologic features of advanced ALK-positive lung cancer, which include smaller-sized primary tumors and higher frequencies of notch and pleural indentation, compared with EGFR/ALK-negative tumors. These findings might be useful for the selection of patients with advanced ALK-positive lung cancer.
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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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P2.04-064 - Microenvironmental Factor of Primary Lung Adenocarcinoma Which Predicts the Effectiveness of Chemotherapy in Patients with Recurrences (ID 815)
09:30 - 09:30 | Author(s): H. Ohmatsu
- Abstract
Background:
The influence of microenvironmental factors on the effectiveness of chemotherapy is being increasingly recognized. Stromal cells in cancer tissue, such as tumor-associated macrophages (TAMs) and cancer-associated fibroblasts (CAFs), have been shown to influence tumor progression. The associations of CD204-positive cells, which represent an M2 phenotype of TAMs, and podoplanin-positive CAFs, which represent a subpopulation of CAFs with a tumor-promoting phenotype, with a poor prognosis have been identified in patients with lung adenocarcinoma, but whether these associations are involved in the response to chemotherapy remains unknown. The purpose of this study was to investigate the relationships between cancer cell and stromal cell phenotypes in primary tumors and the progression-free survival (PFS) of recurrent lung cancer patients who received platinum-based chemotherapy.
Methods:
We retrospectively analyzed 87 postoperative recurrent lung adenocarcinoma patients treated with platinum-based chemotherapy. The expressions of drug resistance-related proteins including BCRP, Ezrin and ALDH1 in cancer cells, the number of CD204-positive TAMs, and the presence of podoplanin-positive CAFs in the primary tumor were examined. The relationships between the immunohistochemical staining results of primary tumors and the PFS after receiving chemotherapy were also analyzed.
Results:
Among the clinicopathological factors of primary tumors, only an advanced pathological stage was significantly associated with a shorter PFS. As for immunohistochemical staining, no significant relationships were found between the PFS and the expression of BCRP, Ezrin, or ALDH1. The number of CD204-positive TAMs was not associated with the PFS. The presence of podoplanin-positive CAFs, identified in thirty (34%) of 87 samples, was significantly associated with a shorter PFS (median PFS: 5.1 vs. 7.8 months, P=0.028), but was not significantly associated with a shorter overall survival (median survival time: 18.1 vs. 23.7 months, P=0.156). A multivariate analysis revealed a tendency of podoplanin-positive CAFs to be correlated with a shorter PFS (P=0.087).
Conclusion:
The presence of podoplanin-positive CAFs in the primary tumor could be a predictor of a shorter PFS in recurrent lung adenocarcinoma patients who received chemotherapy. These findings suggest that stromal-cell derived factors should be incorporated into predictions of the effectiveness of chemotherapy.
