Size Measurement and T-staging of Lung Adenocarcinomas Manifesting as Solid Nodules ≤30 mm on CT: Radiology-Pathology Correlation

doi:10.1016/j.acra.2017.01.009

Academic Radiology

Volume 24, Issue 7, July 2017, Pages 851-859

https://doi.org/10.1016/j.acra.2017.01.009 Get rights and content

Rationale and Objectives

This study aimed to compare long-axis diameter to average computed tomography (CT) diameter measurements of lung adenocarcinomas manifesting as solid lung nodules ≤30 mm on CT, as referenced to pathologic measurements, and to determine the impact of the two CT measurement approaches on tumor (T)-staging of nodules.

Materials and Methods

This institutional review board-approved study included all 274 radiologic solid adenocarcinomas resected at our institution over 10 years. Two observers measured long- and short-axis diameters on pre-resection chest CT in lung and mediastinal windows. T-stages were determined. CT measurements and T-stages were compared to pathology measurements and T-stages using Wilcoxon signed rank test and McNemar test. Inter- and intraobserver variability was determined with intraclass correlation coefficients (ICC) and Bland-Altman plots.

Results

For lung and mediastinal windows, nodule size was significantly larger using long-axis diameter rather than average diameter (16.93 vs. 14.92 mm, P <.001; and 14.02 vs. 12.17 mm, P <.001, respectively). The correlation of CT with pathologic measurements was stronger with long-axis than with average diameter (ICC 0.808 vs. 0.730; and 0.731 vs. 0.621, respectively). Lung window measurements correlated stronger with pathology than mediastinal window measurements. CT T-stages differed from pathology T-stages in more than 20% of nodules (P <.001). Inter- and intraobserver variability was small with long-axis and average diameter (ICC range 0.96–0.991, and 0.970–0.993, respectively), but long-axis diameter showed wider scatter on Bland-Altman plots.

Conclusions

Long-axis CT diameter is preferable for T-staging because it better reflects the pathology T-stage. Average CT diameter might be used for longitudinal nodule follow-up because it shows less measurement variability and is more conservative in size assessment.

Introduction

The size of solid lung nodules detected on computed tomography (CT) has a substantial impact on their management. Indeed, current management guidelines consider nodule size a key parameter for both incidentally detected nodules 1, 2, 3 and those seen in the framework of CT lung cancer screening 2, 3, 4. The approaches to how nodule size is measured and expressed, however, differ. Whereas some authors recommend that the long-axis diameter of a nodule should be used (3), others suggest that the average of long-axis and short-axis diameters should be calculated 1, 4. To date, no general consensus has been reached over which of these two approaches is more accurate.

This may, in part, be caused by the paucity of studies comparing CT measurements of solid nodules to measurements obtained by pathology, which is commonly considered the reference standard for determining nodule size 5, 6. Such comparisons could help quantify potential differences between the two measurement approaches and gauge the consequences that these differences have for the management of solid nodules, notably with respect to tumor (T)-staging.

Higher T-stages reflect more advanced disease and are associated with decreased 5-year survival, that is, 77% (stage T1a), 71% (stage T1b), and 58% (stage T2a), respectively 5, 7. Consequently, management may differ between patients with different T-stages. For example, patients with stage T2b may undergo magnetic resonance imaging of the brain, whereas this is not recommended for patients with stage T1b. Furthermore, high-risk patients with stage T2a receive neoadjuvant chemotherapy, whereas high-risk patients with stage T1b will only be observed (8). Therefore, the purpose of our study was to compare long-axis diameter to average diameter measurements of lung adenocarcinomas (ACs) manifesting as solid lung nodules ≤30 mm on CT, as referenced by pathology measurements, and to determine the impact of the two measurement approaches on the T-staging of the nodules.

Section snippets

Study Material

The study protocol was approved by our institutional review board, and informed consent was waived (protocol-number 15–020). Using our hospital electronic medical record system, we retrieved the files of all patients with a pathologic diagnosis of primary lung AC surgically resected at our institution between January 2005 and March 2015.

The search resulted in 607 resected ACs, which were matched to our hospital's radiology database, to identify those carcinomas with pre-resection CT

Results

The 274 ACs included in the study were present in 259 patients. Fifteen of 259 (5.79%) patients had more than one resected nodule, but no patient had more than two resected nodules. The mean age of the patients was 67 ± 9 years (range, 42–89 years). Of 259 patients, 151 (58.30%) were women (mean age, 67 ± 9 years; range, 42–89 years) and 108 (41.70%) were men (mean age, 67 ± 9 years; range, 47–85 years). No statistically significant difference in age was found between women and men (P = .696).

Discussion

Our study compared long-axis CT diameter to average CT diameter measurements of solid lung nodules, pathologically confirmed to be lung ACs, performed on both lung and mediastinal windows, and referenced to gross pathologic measurements. Our study also aimed to determine the impact of the two measurement approaches on the T-staging of solid lung nodules. Overall, our results showed that CT diameters are systematically smaller than pathology diameters. Our results also showed that T-staging by

Acknowledgment

We thank Donna Wolfe for revision and editing of our manuscript. Benedikt H. Heidinger is the 2016 Sven Paulin Research Fellow in Cardiothoracic Imaging at the Department of Radiology, Beth Israel Deaconess Medical Center, Boston, Massachusetts.

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Discrepancies between radiological whole tumor size (RTS) and pathological whole tumor size (PTS) are sometimes observed. Unexpected pathological upsize may lead to insufficient margins during procedures like sub lobar resections. Therefore, this study aimed to investigate the current status of these discrepancies and identify factors resulting in pathological upsize in patients with early-stage non-small cell lung cancer (NSCLC). Data from a multicenter database of 3092 patients with clinical stage 0-IA NSCLC who underwent pulmonary resection were retrospectively analyzed. Differences between the RTS and PTS were evaluated using Pearson's correlation analysis and Bland-Altman plots. Unexpected pathological upsize was defined as an upsize of ≥1 cm when compared to the RTS, and the predictive factors of this upsize were identified based on multivariable analyses. The RTS and PTS showed a positive linear relationship (r = 0.659), and the RTS slightly overestimated the PTS. The Bland-Altman plot showed 131 of 3092 (5.2%) cases were over the upper 95% limits of agreement. In multivariable analyses, a maximum standardized uptake value (SUV_max) of the primary tumor on 18-fluoro-2-deoxyglucose positron emission tomography/computed tomography (odds ratio [OR], 1.070; 95% confidence interval [CI], 1.035−1.107; P < 0.001) and the adenocarcinoma histology (OR, 1.899; 95% CI, 1.071−3.369; P =0.049) were independent predictors of unexpected pathological upsize. More of the adenocarcinomas with pathological upsize were moderately or poorly differentiated, when compared to those without. The RTS tends to overestimate the PTS; however, care needs to be taken regarding unexpected pathological upsize, especially in adenocarcinomas with a high SUV_max.
Prognostic performance in lung cancer according to tumor size: Comparison of axial, multiplanar, and 3-dimensional CT measurement to pathological size
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This study aimed to compare the prognostic performance of clinical T staging based on axial, multiplanar, and 3-dimensional measurement on CT with that of pathological T staging in patients with non-small cell lung cancer.
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A total of 544 patients (64.7 ± 9.7 years, 352 men) were included; 160 patients (29.4%) experienced events including 29 (5.3%) who expired. The median DFS was 44.1 months. The mean tumor size on axial, multiplanar images, 3-dimensional tumor mask, and pathology was 30.8 ± 17.3, 33.9 ± 19.4, 39.2 ± 21.4, and 33.4 ± 18.0 mm, respectively. Clinical staging based on multiplanar measurement showed a higher agreement (67.5% [367/544]) with pathological staging than axial (60.5% [329/544]) and 3-dimensional measurement (50.9% [277/544]) based staging did (p = .0005 and <.0001, respectively). The adjusted C-indices of axial, multiplanar, 3-dimensional, and pathological tumor stages were 0.66 (95% confidence interval [CI]: 0.66–0.67), 0.66 (95% CI: 0.66–0.66), 0.67 (95% CI: 0.67–0.67), and 0.67 (95% CI: 0.66–0.67), respectively (p > .05).
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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AJCC-UICC guidelines could address additional issues that alters tumor measurements such as those listed in Table 3 to standardize tumor length measurements; for example, window setting for soft tissues, use of intravenous contrast agent, or tumor delineation algorithms (4). The TNM8 manual states contrast CT tends to increase the apparent size of a tumor, but only ∼50% of the patients have historically been administered a contrast agent, so that it is not clear if contrast CT will become the norm (4). Yet other more-modest issues, the radiation dose, and smooth versus sharp CT image reconstruction algorithms also affect the apparent in-plane measured size of a tumor (47).
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.
By including preliminary non–small cell lung cancer clinical stage values in their evaluation, diagnostic radiologists can improve the accuracy of staging and standardize tumor-size measurements, which improves patient care.
Growth Assessment of Pulmonary Adenocarcinomas Manifesting as Subsolid Nodules on CT: Comparison of Diameter-Based and Volume Measurements
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To analyze the performances of diameter-based measurements, either using diameters, or by calculating diameter-based volumes, as compared to volume measurements in assessing growth of pulmonary adenocarcinomas manifesting as subsolid nodules on CT.
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There were fewer growing nodules during CT1-CT2 interval (n = 22, 30%) than during CT2-CT3 interval (n = 33, 45%, p =.060). Specificity and negative predictive value of diameter-based measurements for growth assessment ranged respectively from 52 to 77% and 81 to 83% between CT1 and CT2, and from 66 to 76% and 79 to 90% between CT2 and CT3. Nongrowing nodules tended to be larger, regardless how size was measured, and some of these differences in size were statistically significant (p =.002 to .046).
For pulmonary adenocarcinomas presenting as subsolid nodules on CT, diameter-based assessment of nodule volume is reasonably accurate at confirming a lack of nodule growth but may overestimate actual growth, as compared to growth assessment based on measured volume.
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Among cancers, lung cancer is the leading cause of cancer deaths. For non-small cell lung cancer (NSCLC), pathological staging and tumor size measurements have historically been considered more accurate and are the reference standard by which the clinical values are compared [1-6]. However, 80% of NSCLC are not treated surgically and do not have pathological staging so that accurate clinical assessment, alone, is critical.
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.
The concordance for clinical versus pathological lymph node N-stage is very good, 83.4 ± 1.0%, but the tumor length-location T-stage is only 58.1 ± 0.9%. There are intuitive insights to the causes of discordance. Approximately 29% of the cases are pathological T-stage greater than clinical T-stage, and 12% lower than the clinical T-stage, which is due partly to the fact that surgically-treated NSCLC are typically lower-stage cancer cases, which results in a bounded higher probability for pathological upstaging. Individual T-stage categories Tis, T1a, T1b, T2a, T2b, T3, T4 invariant percent-concordances are 85.2 ± 9.7 + 10.3%; 72.7 ± 1.6 + 11.3%; 46.6 ± 1.8 + 10.9%; 54.6 ± 1.6 – 20.5%; 41.6 ± 3.3 – 0.1%; 54.7 ± 2.8 – 24.1%; 55.2 ± 4.7 + 2.6%, respectively. Each percent-concordance is referenced to an averaged number of pathological and clinical cases. The first error number quantifies statistical fluctuations; the second quantifies clinical and pathological staging biases. Lastly, comparison of over and under staging versus clinical characteristics provides further insights.
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2017, Academic Radiology
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The 503 pulmonary nodules on which the current study was based were part of our hospital's data repository of pathologically confirmed resected pulmonary adenocarcinomas. This data repository served for other studies on different topics, with a partial overlap of lesions and patients (4–7). Inclusion and exclusion criteria of nodules had been previously published (4).
The objective of this study was to quantify the impact of different rounding methods on size measurements of pulmonary nodules and to determine the number of nodules that change management categories as a result of rounding.
For this retrospective institutional review board-approved study, we included 503 incidental pulmonary nodules (308 solid and 195 subsolid) from a data repository. Long and short axes were measured. Average diameters were calculated using four different rounding methods (method 1: no rounding; method 2: rounding only the average diameter to the closest millimeter; method 3: rounding only short and long axes; and method 4: rounding short and long axes and the average diameter to the closest millimeter). Nodules were classified for each rounding method according to the 2017 Fleischner Society guideline management categories. Measurements were compared among the four rounding methods using analysis of variance.
Without rounding, the average nodule diameter was 15.67 ± 5.97 mm. This increased between 0.03 and 0.29 mm using rounding methods 2–4 (range: P < 0.001–0.017). The nodule size was more frequently rounded up (range: 52.1%–77.5%) than rounded down (range: 17.7%–42.5%) using rounding methods 2–4, as compared to no rounding. In the 308 solid nodules, up to 2.9% of the nodules changed management category, whereas none of the 195 subsolid nodules changed category.
Rounding methods have a small absolute but statically significant effect on nodule size, impacting management category in less than 3% of the nodules. This suggests that, in clinical practice, any rounding method can be used for determining nodule size without substantially biasing individual nodules toward given management categories.

View all citing articles on Scopus

: The study protocol was approved by our institutional review board and informed consent was waived (protocol number 15–020).

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Original InvestigationSize Measurement and T-staging of Lung Adenocarcinomas Manifesting as Solid Nodules ≤30 mm on CT: Radiology-Pathology Correlation

Rationale and Objectives

Materials and Methods

Results

Conclusions

Introduction

Section snippets

Study Material

Results

Discussion

Acknowledgment

J Thorac Oncol

Lancet

Lung Cancer

Lung Cancer

Eur J Radiol

Ann Thorac Surg

Guidelines for management of small pulmonary nodules detected on CT scans: a statement from the Fleischner Society

Radiology

Evaluation of individuals with pulmonary nodules: when is it lung cancer? Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines

Chest

British Thoracic Society guidelines for the investigation and management of pulmonary nodules

Thorax

ACR-STR practice parameter for the performance and reporting of lung cancer screening thoracic computed tomography (CT): 2014 (Resolution 4)

J Thorac Imaging

AJCC cancer staging manual

The stage classification of lung cancer: diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines

Chest

Clinical Practice Guidelines in Oncology: Non-Small Cell Lung Cancer

Measurement bias of gross pathologic as compared to radiologic tumor size of resected lung adenocarcinomas; implications for the T-Stage revisions in the 8th edition of the AJCC Cancer Staging Manual

Am J Clin Pathol

Fleischner society: glossary of terms for thoracic imaging

Radiology

Original Investigation
Size Measurement and T-staging of Lung Adenocarcinomas Manifesting as Solid Nodules ≤30 mm on CT: Radiology-Pathology Correlation