Prognostic value of ground-glass opacity found in small lung adenocarcinoma on high-resolution CT scanning

doi:10.1016/S0169-5002(01)00185-4

Lung Cancer

Volume 33, Issue 1, July 2001, Pages 17-25

https://doi.org/10.1016/S0169-5002(01)00185-4 Get rights and content

Abstract

Objective: This study was undertaken to investigate the value of the ground-glass opacity (GGO) area found on high-resolution computed tomography (HRCT) scanning as a preoperative prognostic indicator. Patients and methods: We studied 104 patients with small-sized lung adenocarcinoma, 20 mm or less in diameter, between 1995 and 1999. Three independent radiologists semi-quantitatively scored the extent of GGO on HRCT as greater than or less than 50%. Three independent pathologists semi-quantitatively scored the extent of the bronchioloalveolar carcinoma (BAC) component of the tumor on histologic examination as greater than or less than 50%. As no relapse occurred in patients with GGO greater than 50%, multivariate analysis of this prognostic factor was not possible. Results: Fifty patients were scored as having both BAC and GGO greater than 50%, 36 as both BAC and GGO less than 50%, and 16 as BAC greater than 50% and GGO less than 50%. In only two patients (1.9%), BAC less than 50% was overestimated on HRCT as GGO greater than 50%. The sensitivity and specificity of GGO to BAC were 76 and 95%, respectively. The 3 year-relapse-free survival rates in each group of 52 patients with GGO greater than and less than 50% were 100 and 72%, respectively, after a median follow-up of 24 months. Univariate analysis indicated that both GGO and BAC areas were significantly correlated with cancer relapse (P=0.005 and P=0.002). The multivariate analysis revealed an independent prognostic influence of the BAC area on relapse-free survival (P=0.015, relative risk=0.07). Conclusions: To date there has been no relapse among the 52 patients with GGO greater than 50%. This novel classification based on the semiquantitative analysis of GGO area on HRCT should become an useful independent preoperative indicator when deciding on operative procedure, and to predict the potential of relapse in patients with small adenocarcinoma arising from the peripheral lung.

Introduction

Recently, low-dose X-ray spiral computed tomography (CT) scanning of the lung has improved the likelihood of detection of small non-calcified nodules, and thus of lung cancer at an earlier and potentially more curable stage [1], [2]. When the small nodules include a component of so-called ground-glass opacity (GGO) on high-resolution CT (HRCT) scanning, adenocarcinoma is suspected [3], [4].

In April 1999, the newly revised third edition of WHO concerning histological typing of lung tumors was published [5]. According to the new classification, lung adenocarcinoma was divided into five categories. Among them, bronchioloalveolar carcinoma (BAC) is classified as non-invasive carcinoma, and tumors with both non-invasive and invasive components are classified as adenocarcinoma with mixed subtype. Lymph node and hematogenous metastases are quite rare among such non-invasive or slightly-invasive carcinomas of the lung.

In our previous study [6], we concluded that the proportion of BAC components involving small peripheral lung adenocarcinoma may reflect clinicopathological and prognostic characteristics, and the semiquantitative assessment of the BAC area may prove valuable when planning therapeutic strategies, particularly surgical treatment. We hypothesized that the histological BAC area must be reflected as GGO on HRCT.

The purpose of this study was to elucidate the correlation between the histological BAC area and GGO area on HRCT in small peripheral adenocarcinoma, and to determine the value of semiquantitative assessment of the GGO area within a tumor, as a preoperative indicator for the planning of surgical procedure.

Section snippets

Patients and methods

From February 1995 to October 1999, 519 non-small-cell lung cancer (NSCLC) patients underwent operations in our institute. Of these, 104 patients with peripheral small-sized adenocarcinoma 20 mm or less in diameter on HRCT were retrospectively analyzed in the present study (Table 1). Of the 104 patients, 55 were male, and 49 were female. The mean age was 60 years (range, 34–78 years). The maximal tumor diameter measured on HRCT was 10 mm or less in 33 patients, 11–15 mm in 41 patients, and more

Results

Table 2 shows the correlation between the histological BAC component and GGO component on HRCT. Fifty patients were included in the category with both BAC and GGO greater than 50% (sensitivity=76%). Conversely, 36 patients were included into the category with both BAC and GGO less than 50% (specificity=95%). There were 16 patients with BAC greater than 50% and GGO less than 50%. Only two patients were included in the category with BAC less than 50% and GGO greater than 50%. Good agreement was

Discussion

Besides the TNM staging, a number of prognostic indicators have been proposed [8], [9], [10], [11], [12]. They included not only conventional clinico–pathological indicators such as tumor differentiation [8], pleural involvement [8], status of vascular and lymphatic invasion [10] and mitotic index [9], but also molecular indicators such as K-ras [10], p53 [11], factor Viii [11], erB-b2 [11], CD44 [11] and telomerase activity [12]. However, the details of these results are only available after

Conclusion

Although the follow-up period was relatively short, this novel classification based on semiquantitative analysis of the GGO area may reflect the tumor character and become an useful independent preoperative indicator in deciding the operative procedure in patients with small adenocarcinoma of the lung.

Acknowledgments

This study was partially funded by a Grant-in-Aid for Cancer Research (9–18) from the Ministry of Health and Welfare, Japan.

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Recent studies have suggested that including presence or absence of ground-glass opacity (GGO) may improve the tumor descriptor (T descriptor) classification in clinical stage I NSCLC. In this study, we analyzed prognostic implications of presence or absence of GGO, size of the solid component, and predominant histology to identify the true prognostic determinant for early-stage NSCLC.
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Citation Excerpt :
For PRE and MIA, patients would have near 100% disease-free survival if these lesions were completely resected.11,12 In previous studies, most GGO-dominant lung adenocarcinoma was reported to be PRE or MIA, both of which are suitable for sublobar resection13–16; however, lung adenocarcinoma with a GGO component occasionally exhibits pathological invasiveness. Therefore, accurate preoperative prediction of lung adenocarcinoma aggressiveness is crucial for the selection of the appropriate surgical procedure.
This study evaluated the relationship between three-dimensional (3D) mean computed tomography (CT) attenuation values of ground-glass nodules (GGN) and pathological invasiveness in early lung adenocarcinoma. The diagnostic accuracy of 3D CT attenuation values was compared with that of two-dimensional (2D) CT attenuation values and standardised uptake value on positron-emission tomography (PET).
Surgical and radiological data from 96 pure or part-solid GGNs of <20 mm were analysed retrospectively. Mean 2D and 3D CT attenuation values of the tumours were obtained with semi-automated volumetric software. Pathological invasiveness was diagnosed according to the International Association for the Study of Lung Cancer (IASLC))/American Thoracic Society (ATS)/European Respiratory Society (ERS) classification. Pre-invasive lesions and minimally invasive adenocarcinomas were classified as non-invasive adenocarcinoma. Univariate and multivariate analyses determined relationships between pathological invasiveness and clinical/radiological findings. Receiver operating characteristic (ROC) analysis was performed to determine the optimal cut-off value for detecting invasive adenocarcinoma.
A total of 66 non-invasive and 30 invasive adenocarcinoma cases between 2010 and 2016 were analysed. Univariate analysis revealed four tumour invasiveness-associated predictors: maximum diameter, SUVmax, mean 2D CT attenuation value, and mean 3D CT attenuation value (p<0.05). Multivariate analysis revealed that the maximum diameter, SUVmax, and mean 3D CT attenuation value were significant predictors of pathological invasiveness (p=0.023, 0.022, 0.004). The area under the ROC curve to predict invasive adenocarcinoma for mean 3D CT attenuation value was 0.838 and the cut-off value was –489 HU.
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Prognostic value of ground-glass opacity found in small lung adenocarcinoma on high-resolution CT scanning

Abstract

Introduction

Section snippets

Patients and methods

Results

Discussion

Conclusion

Acknowledgments

Lancet

Lancet

Ann. Thorac. Surg.

Ann. Thorac. Surg.

J. Thorac. Cardiovasc. Surg.

J. Thorac. Cardiovasc. Surg.

J. Thorac. Cardiovasc. Surg.

J. Thorac. Cardiovasc. Surg.