Rationale and Objectives
The study aimed to assess the relationship between tumor marker index (TMI) and high-resolution computed tomography features in early-stage lung adenocarcinoma.
Materials and Methods
Seventy-four stage IA lung adenocarcinomas confirmed pathologically were retrospectively evaluated. Lung nodules were divided into two types: solid nodule (SN) and subsolid nodule (SSN). The maximum diameters on mediastinal window in axial imaging (D m ) and tumor shadow disappearance rate (TDR) were measured. Meanwhile, other computed tomography features of lung nodules were also recorded. TMI represents the geometric mean of normalized CEA and CYFRA 21-1 values, and the discriminatory value of TMI in this study was set at 1.0. The evaluation of discriminatory values for D m and the TMI between SNs and SSNs was done with Mann-Whitney U -test. The relationship between TDR and TMI in SSNs was evaluated by Pearson correlation analysis.
Results
Of 74 cases, 40 cases (54.05%) showed SNs and 34 cases (45.95%) showed SSNs. D m and TMI were higher in SNs than in SSNs (z = −4.782, P < 0.001; z = −2.647, P = 0.008). TDR demonstrated negative relationship with TMI in SSNs (r = −0.448, P = 0.008). Spiculation (odds ratio [OR] = 14.685; 95% confidence interval [CI]: 2.739–78.729; P = 0.002), nodule type (OR = 6.215; 95% CI: 1.531–25.228; P = 0.011), and gender (OR = 0.227; 95% CI: 0.062–0.833; P = 0.025) were independent factors associated with TMI.
Conclusions
Early-stage lung adenocarcinoma with lower TDR coexisting with spiculation was associated with higher TMI, especially in patients with solid nodule, which tended to have poor prognosis.
Introduction
Non-small cell lung cancer (NSCLC) approximately accounts for 85% of lung cancer cases , which is one of the most prevalent and cancer-related death worldwide. For highly treatment refractory rate, considerable effort is currently devoted to NSCLC-related research area. However, early detection and surgical resection remain a primary way of improving the survival of NSCLC patients . Although pathologic stage IA (T1N0M0) NSCLC is able to be completely resected theoretically, postoperation survival rate is significantly variable (60–85%) in current clinical practice . In the quest to improve prognosis, reliable prognostic markers are required in order to select the best possible treatment for individual lung cancer patients who could benefit from neoadjuvant chemoradiotherapy for high-risk groups after operation. Thus, in addition to the tumor, node, and metastasis(TNM) stage, other factors with predictive value for prognosis, such as pathologic characteristics, imaging features, serum tumor markers, and molecular markers, are widely evaluated in clinical practice.
Pretreatment serum carcinoembryonic antigen (CEA) and cytokeratin 19 fragments (CYFRA21-1) are well-established serum tumor markers used for NSCLC, used as indicators of treatment response to improve the clinical outcomes of lung cancer patients. However, their evaluation when used in combination is often difficult. A prognostic score that is based on both tumor marker values—the tumor marker index (TMI)—was then introduced by Muley et al. . TMI is useful for predicting the prognosis of early-stage NSCLC patients and might help identify patients who are likely to benefit from adjuvant therapy .
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Materials and Methods
Study Group
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Table 1
Summary of Computer Tomography Features and Patients’ Clinical Characteristics ( n = 74)
Factors Numbers/Values Factors Numbers/Values Patient age (year) 61.61 ± 9.21 Coexistence with bullae/honeycomb (no.) Gender (no.) Yes 13 (13/74; 17.57%) Male 35 (35/74; 47.30%) No 61 (61/74; 82.43%) Female 39 (39/74; 52.70%) Air bronchogram (no.) Smoking status (no.) Yes 23 (23/74; 31.08%) Smokers 22 (22/74; 29.73%) No 51 (51/74; 68.92%) Non-smokers 52 (52/74; 70.27%) TDR SSN (%) 35.16 ± 23.73 Nodule type (no.) Max D media (cm) 2.61 ± 1.16 SN 40 (40/74; 54.05%) Preoperative serum CEA (no.) SSN 34 (34/74; 45.95%) ≥5.0 ng/mL 17 (17/74; 22.97%) Lobulation (no.) <5.0 ng/mL 57 (57/74; 77.03%) Yes 70 (70/74; 94.59%) Preoperative serum CYFRA21-1 (no.) No 4 (4/74; 5.41%) >3.3 ng/mL 27 (27/74; 36.49%) Spiculation (no.) ≤3.3 ng/mL 47 (47/74; 63.51%) Yes 42 (42/74; 56.76%) TMI (no.) No 32 (32/74; 43.24%) >1.0 23 (23/74; 31.08%) Pleural based (no.) ≤1.0 51 (51/74; 68.92%) Yes 13 (13/74; 17.57%) Surgical procedure (no.) No 61 (61/74; 82.43%) Single-side pneumonectomy 1 (1/74; 1.35%) Pleural indentation (no.) Lobectomy 67 (67/74; 90.54%) Yes 40 (40/74; 54.05%) Segment resection 2 (2/74; 2.70%) No 34 (34/74; 45.95%) Wedge resection 4 (4/74; 5.41%)
CEA, carcinoembryonic antigen; CYFRA 21-1, cytokeratin 19 fragments; SN, solid nodule; SSN, subsolid nodules; TDR, tumor shadow disappearance rate; TMI, tumor marker index.
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Serum Tumor Markers
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CT Scan and Image Analysis
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![Figure 1-2, Illustration on how to measure the tumor shadow disappearance rate (TDR). The maximum tumor diameter (D) and the largest diameter perpendicular to D (perD) on lung window (left) is 27.5 mm and 25.0 mm, and that on mediastinal window (right) is 19.6 mm and 15.8 mm. TDR is calculated by the following formula: [1 − (19.6 × 15.8)/(27.5 × 25)] × 100% ≈ 45%.](https://storage.googleapis.com/dl.dentistrykey.com/clinical/AssessmentofRelationshipBetweenCTFeaturesandSerumTumorMarkerIndexinEarlystageLungAdenocarcinoma/0_1s20S1076633216301295.jpg)
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Pathology Evaluation
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Statistical Analysis
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Results
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Table 2
Computed Tomography Features and Clinical Characters of Different TMI Subgroups
Factors TMI_P_ Value χ 2 >1.0 ≤1.0 Max D media 0.069 3.309 ≥1.5 cm 20 (27.03%) 34 (45.95%) <1.5 cm 3 (4.05%) 17 (22.97%) Air bronchogram 0.037 0.368 Yes 11 (14.86%) 12 (16.22%) No 12 (16.22%) 39 (52.70%) Pleural indentation 0.001 10.956 Yes 19 (25.68%) 21 (28.38%) No 4 (5.41%) 30 (40.54%) Spiculation 0.007 7.235 Yes 22 (29.73%) 20 (27.03%) No 1 (1.35%) 31 (41.89%) Lobulation 0.409 0.682 Yes 23 (31.08%) 47 (63.51%) No 0 (0%) 4 (5.41%) Pleural-based 0.196 1.673 Yes 6 (8.11%) 7 (9.46%) No 17 (22.97%) 44 (59.46%) Coexistence with bulla/honeycomb 0.762 0.092 Yes 5 (6.76%) 8 (10.81%) No 18 (24.32%) 43 (58.11%) Nodule type <0.001 14.547 SN 20 (27.03%) 20 (27.03%) SSN 3 (4.05%) 31 (41.89%) Age (years) 0.228 1.455 >70 6 (8.11%) 6 (8.11%) ≤70 17 (22.97%) 45 (60.81%) Gender 0.038 4.299 Female 15 (20.27%) 20 (27.03%) Male 8 (10.81%) 31 (41.89%) Smoking status 0.022 5.231 Smokers 11 (14.86%) 11 (14.86%) Non-smokers 12 (16.22%) 40 (54.05%)
Max D media, axial maximum diameters on mediastinal window; SN, solid nodule; SSN, subsolid nodule; TMI, tumor marker index.
Table 3
Independent Factors Associated with High TMI (>1.0)
Factors OR (95% CI)P Spiculation 14.685 (2.739–78.729) 0.002 Nodule type 6.215 (1.531–25.228) 0.011 Gender 0.227 (0.062–0.833) 0.025 Max D media NA 0.359 Pleural indentation NA 0.507 Air bronchogram NA 0.521 Smoking status NA 0.794
CI, confidence interval; OR, odds ratio; TMI, tumor marker index.
Binary logistic regression analysis with forward conditional method.
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Discussion
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Acknowledgment
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