Correlation between tumor measurement on Computed Tomography and resected specimen size in lung adenocarcinomas

doi:10.1016/j.lungcan.2011.08.001

Lung Cancer

Volume 75, Issue 3, March 2012, Pages 332-335

https://doi.org/10.1016/j.lungcan.2011.08.001 Get rights and content

Abstract

Objective

To compare preoperative size of stage I and stage II lung adenocarcinoma as measured by Computed Tomography (CT) and as assessed on gross pathology specimens.

Materials and methods

47 patients diagnosed with stage I or II lung adenocarcinoma were evaluated. Institutional Review Board permission was obtained. Tumor contours were delineated using a semi-automated segmentation algorithm and adjusted based on a radiologist's input. Based on the tumor perimeter, maximal in-plane tumor diameter was calculated automatically. The largest single diameter from the pathology gross report was utilized. A paired t-test was used to examine the measurement difference between CT and pathology.

Results

The mean largest diameter of the tumors at CT and pathology was 29.53 mm and 24.04 mm, respectively. There was a statistically significant difference between the mean CT measurement and mean pathology measurement of 5.49 mm (standard deviation 9.08 mm, p < 0.001). The percent relative difference between the two measurements was 18.3% (standard deviation 28.2%).

Conclusion

There is a statistically significant difference between the tumor diameter as measured by CT and on pathology gross specimen. These differences could have implications in the treatment and prognosis of patients with early stage lung adenocarcinoma.

Introduction

Lung cancer is the leading cause of cancer deaths in the United States. The 5 year survival rate for non-small cell lung cancer (NSCLC) remains poor: clinical stage I surgically resectable lung cancer carries a 5 year survival rate of 50%, and clinical stage II NSCLC carries a 5 year survival rate of 30% [1]. The staging of lung cancer is vital, as it guides a patient's therapy and determines prognosis; yet its accuracy is disputed [2]. For example, patients with stage I or II NSCLC benefit from surgical resection, whereas patients with stage IIIB cancer or greater are not candidates for surgery [1].

The American Joint Committee on Cancer (AJCC) revised the TNM classification of lung cancer in the new 7th edition cancer staging manual [3]. Modifications to the staging system were adapted because there have been multiple studies that confirm the importance of differentiating tumors that are ≤2 cm, 2–3 cm, 3–5 cm and ≥5 cm in maximum dimension [2], [4], [5], [6], [7]. Previously, tumors were not subclassified by size under or above 3 cm. These seemingly small differences in maximum dimension play important roles in prognosis [2], [4], [5], [6], as patients are clinically staged based on maximal diameter on CT.

To our knowledge, there are only a few studies that actually correlate radiologic size of a lung tumor with the size as determined by the pathology gross specimen. Surgically resected patients’ staging will ultimately be based on the pathologic measurements. Several studies have compared various aspects of clinical and pathologic stage, such as tumor size (T descriptor), nodal status (N), pathology specimen characteristics, and diagnostic accuracy with PET and integrated PET/CT [6], [8], [9], [10], [11]. However, few studies specifically examine the pathologic–radiologic concordance of size of tumors, which is particularly important given that the majority of modifications to the staging system focused on the T status.

The goal of our study is to compare the radiologic preoperative size of solitary stage I and II lung adenocarcinoma with their pathologic size following excision.

Section snippets

Patients

The Institutional Review Board granted approval for our retrospective study. Data was collected and handled in accordance with the Health Insurance Portability and Accountability Act regulations. Fifty patients with stage I or II lung adenocarcinoma were studied as part of a larger study correlating radiographic response to a chemotherapy regimen. Participating patients had tumors that were determined to be operable and resectable by the treating surgeons and had measurable indicator lesions on

Results

Of the 50 patients enrolled in the initial study, 47 were included in our study. One patient was excluded because the patient had resection at an outside institution with only microscopic portions of the lesion submitted for review, and the gross largest diameter was not provided. The two other patients were excluded because the CT thin section images for the calculation of volumetric size were not available.

The mean diameter of CT largest dimension was 29.53 mm (Table 1). The mean of the

Discussion

There is very little data on the degree of measurement error for CT measurements. In fact, there currently is no established “gold standard” for tumor dimensions. Our study demonstrates that there is indeed a significant difference between CT preoperative size of a tumor and its pathologic size. CT measurements tended to “overestimate” the true pathologic size, which may result in upstaging. The reason for CT “overestimation” of size may be multi-factorial. CT measurements were based upon

Sources of support

None.

Conflict of interest statement

None declared

No actual or potential conflicts of interest, including financial, personal, or other relationships with other people or organizations that could inappropriately influence the work.

References (18)

P. Groome et al.
The IASLC lung cancer staging project: validation of the proposals for revision of the T,N, M descriptors and consequent stage groupings in the forthcoming (seventh) edition of the TNM classification of malignant tumors
Journal of Thoracic Oncology
(2007)
P. Goldstraw et al.
The IASLC lung cancer staging project: proposals for the revision of the TNM stage groupings in the forthcoming (seventh) edition of the TNM classification of malignant tumors
Journal of Thoracic Oncology
(2007)
S.I. Ou et al.
Prognostic significance of the non size-based AJCC T2 descriptors: visceral pleura invasion, hilar atelectasis, or obstructive pneumonitis in stage IB non-small cell lung cancer is dependent on tumor size
Chest
(2008)
R. Milroy
Staging of lung cancer
Chest
(2008)
A. Gajra et al.
Impact of tumor size on survival in stage Ia non-small cell lung cancer: a case for subdividing stage Ia disease
Lung Cancer
(2003)
H.M. Yu et al.
Evaluation of gross tumor size using CT, 18-F-FDG PET, and integrated 18-F-FDG PET/CT and pathological analysis in non-small cell lung cancer
European Journal of Radiology
(2009)
G. Silvestri et al.
Noninvasive staging of non-small cell lung cancer: ACCP evidenced-based clinical practice guidelines (2nd edition)
Chest
(2007)
C. Casali et al.
The prognostic impact of tumor size in resected stage I non-small cell lung cancer: evidence for a two thresholds tumor diameters classification
Lung Cancer
(2006)
T.H. Kim et al.
Pleomorphic carcinoma of the lung: comparison of CT features and pathologic findings
Radiology
(2004)

There are more references available in the full text version of this article.

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The prognostic performances of tumor staging according to size measurement methods were not significantly different. Multiplanar measurement may be preferable for clinical staging considering its highest agreement with pathological staging.
Clinical Non–Small Cell Lung Cancer Staging and Tumor Length Measurement Results From U.S. Cancer Hospitals
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Table 3 lists some potential clinical sources of biases that affect the accuracy of clinical tumor length measurements, such as tumor delineation. Nevertheless, both clinical and pathological measurement biases exist (4,6,11,13,14,19–39). It is difficult to pinpoint which may cause the largest size disagreement.
Examine the accuracy of clinical non–small cell lung cancer staging and tumor length measurements, which are critical to prognosis and treatment planning.
Compare clinical and pathological staging and lengths using 10,320 2016 National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) and 559 2010–2018 non-SEER single-institute surgically-treated cases, and analyze modifiable causes of disagreement.
The SEER clinical and pathological group-stages agree only 62.3% ± 0.9% over all stage categories. The lymph node N-stage agrees much better at 83.0% ± 1.0%, but the tumor length-location T-stage agrees only 57.7% ± 0.8% with approximately 29% of the cases having a greater pathology than clinical T-stage. Individual T-stage category agreements with respect to the number of pathology cases are Tis, T1a, T1b, T2a, T2b, T3, T4: 89.9% ± 10.0%; 78.7% ± 1.7%; 51.8% ± 1.9%; 46.1% ± 1.3%; 40.5% ± 3.1%; 44.1% ± 2.2%; 56.4% ± 4.7%, respectively. Most of the single-institute results statistically agree with SEER's. Excluding Tis cases, the mean difference in SEER tumor length is ∼1.18 ± 9.26 mm (confidence interval: 0.97–1.39 mm) with pathological lengths being longer than clinical lengths except for small tumors; the two measurements correlate well (Pearson-r >0.87, confidence interval: 0.86–0.87). Reasons for disagreement include the use of family-category descriptors (e.g., T1) instead of their subcategories (e.g., T1a and T1b), which worsens the T-stage agreement by over 15%. Disagreement is also associated with higher tumor grade, larger resected specimens, higher N-stage, patient age, and periodic biases in clinical and pathological tumor size measurements.
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Hospitals lack intuitive methods to monitor their accuracy of clinical cancer staging, which is critical to treatment planning, prognosis, refinements, and registering quality data.
We introduce a tabulation framework to compare clinical staging with the reference-standard pathological staging, and quantify systematic errors. As an example, we analyzed 9,644 2016 U.S. National Cancer Institute SEER surgically-treated non-small cell lung cancer (NSCLC) cases, and computed concordance with different denominators to compare with incompatible past results.
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Correlation between tumor measurement on Computed Tomography and resected specimen size in lung adenocarcinomas

Abstract

Objective

Materials and methods

Results

Conclusion

Introduction

Section snippets

Patients

Results

Discussion

Sources of support

Conflict of interest statement

Journal of Thoracic Oncology

Journal of Thoracic Oncology

Chest

Chest

Lung Cancer

European Journal of Radiology

Noninvasive staging of non-small cell lung cancer: ACCP evidenced-based clinical practice guidelines (2nd edition)

Chest

The prognostic impact of tumor size in resected stage I non-small cell lung cancer: evidence for a two thresholds tumor diameters classification

Lung Cancer

Pleomorphic carcinoma of the lung: comparison of CT features and pathologic findings

Radiology