Risk score to preoperatively predict tnm in gastric cancer


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Risk score to preoperatively predict tnm in gastric cancer

  1. 1. ORIGINAL ARTICLE A Risk Score System to Preoperatively Predict TNM Stages in Gastric Cancer Yixin Chen, MD,* and Linjun Mou, MD† the likelihood of R0 resection.4,5 Thus accurate preoperative staging Background: To improve the estimation of tumor status and facilitate the is essential to treatment decision-making. stage-dependent treatment planning, we developed a reliable and easy-to-use Currently, endoscopic ultrasonography (EUS) and helical risk score for prediction of tumor-node-metastasis stages in gastric cancer. computerized tomography (CT) are the mainstays in estimating Methods: Clinicopathological data were collected prospectively from 108 tumor-node-metastasis (TNM) stages of gastric cancer. The diag- curatively resected patients with gastric cancer. The risk score was nostic accuracy of EUS ranged between 67% and 92% for T staging, established on the basis of independent predictive factors for tumor and between 50% and 87% for N staging.7 Helical CT achieved stages, and its performance was evaluated by receiver operating charac- similar results, with accuracy of 55% to 87% for T staging and 52% teristic (ROC) analysis. to 71% for N staging.8 –11 Because the reported accuracy from both Results: The following 4 independent factors were included in our score: imaging procedures was quite variable, there is a need for a better serum albumin levels, tumor size, T and N categories determined by helical and more reliable method to evaluate the extent of tumor. Besides computed tomography. Using ROC analysis, we chose a score at 7 as the imaging findings, some other clinicopathological information is also optimal cut point for differentiating the more advanced disease (stage III/IV) necessary to be taken into account when assessing the stage of from the less advanced one (stage I/II). With the defined cut point, our score disease.12 To improve the estimation of tumor status and facilitate allowed predicting stage III/IV with sensitivity of 79.6%, specificity of the stage-dependent treatment planning, we established a reliable 85.2%, and accuracy of 82.4%. The discriminative ability of this score was and easy-to-use risk score for prediction of TNM stages in gastric good (the area under the ROC curve, 0.861– 0.965). cancer. The risk score, which incorporated imaging findings as well Conclusions: The risk score may be helpful to preoperative gastric cancer as clinicopathological features, was developed from a prospective staging. It probably assists surgeons in deciding the extent of surgery and in cohort of 108 patients with gastric cancer. choosing the appropriate perioperative adjuvant therapies. Key Words: gastric cancer, TNM stages, risk score, helical computerized MATERIALS AND METHODS tomography (Am J Clin Oncol 2010;XX: 000 – 000) Patients A series of 125 consecutive patients underwent curative gastrectomy (R0 resection according to the International Union Against Cancer UICC 13) for primary gastric cancer at the Depart- G astric cancer is the second leading cause of cancer-related death worldwide.1 Despite the advances in surgical techniques, the prognosis of advanced gastric cancer (stage III/IV) remains unsat- ment of Surgery, First Affiliated Hospital of Zhejiang University from March 2006 to July 2007. To be eligible for participation, patients had to have histologically confirmed adenocarcinoma of the isfactory.2,3 A recent survey on 11,491 patients with gastric cancer stomach without previous or coexisting cancer. None had received showed that stage-specific 5-year survival rates were 92.9% for preoperative radiation therapy or chemotherapy. Patients with con- stage Ia, 84.2% for stage Ib, 69.3% for stage II, 45.8% for stage IIIa, comitant disease suspected of affecting hemoglobin concentration, 29.6% for stage IIIb, and 9.2% for stage IV. The recurrence rate platelet count, and serum albumin levels (ie, severe inflammatory after curative gastrectomy (UICC R0 resection) was reported to be conditions, diabetes mellitus or metabolic syndrome) were excluded approaching 60%.3 These poor outcomes obtained by surgery alone from the study. Overall 108 eligible patients were enrolled for have prompted investigation of novel therapeutic strategies. construction of the score. There were 74 men and 34 women with a R0 resection combined with perioperative adjuvant therapy median age of 59 years (ranging from 32 to 85 years). All clinico- has become a promising treatment modality for gastric cancer.4,5 On pathological features were prospectively documented, including the one hand, patients with gastric cancer with R0 resection had a far demographic data, tumor (T) and node (N) categories determined by better 5-year survival rate than those with noncurative operation helical CT, preoperative hemoglobin concentration, platelet count, (55.5% vs. 18.4%).6 R0 resection is assumed to be the primary goal serum albumin values, tumor size and location estimated by gastro- of patient management. An ideal way of achieving R0 resection is to intestinal endoscopy, histologic differentiation and pathologic TNM perform stage-dependent surgery for each patient, in whom the (pTNM) stages. As for the histologic classification, well and mod- extent of surgical resection was determined by the tumor stage. On erately differentiated tubular adenocarcinoma and papillary adeno- the other hand, perioperative adjuvant therapy was found to have a carcinoma were grouped as differentiated type; poorly differentiated beneficial effect on locally advanced gastric cancer (stage III/IV). It adenocarcinoma, signet ring cell carcinoma and mucinous adeno- could induce tumor downstaging and thereby potentially increase carcinoma were grouped as undifferentiated type.14 Postoperative pTNM classification followed the 1997 UICC criteria.13 From the *Department of Surgery, Hangzhou Traditional Chinese Medicine The institutional review board approved this protocol and all Hospital, China; and †Department of Surgery, First Affiliated Hospital, participants gave written informed consent. Zhejiang University School of Medicine, China. Reprints: Linjun Mou, MD, Department of Surgery, First Affiliated Hospital, CT Imaging Zhejiang University School of Medicine, #79 Qingchun Rd, Hangzhou, Helical CT scanning with 5 mm section thickness was per- People s Republic of China 310003. E-mail: chenyx1999@126.com. Copyright © 2010 by Lippincott Williams & Wilkins formed on all patients by a Somatom Plus 4 scanner (Siemens, ISSN: 0277-3732/10/0000-0001 Erlangen, Germany). The patients had to fast for at least 8 hours DOI: 10.1097/COC.0b013e3181d31eeb before the examination. After receiving an intravenous infusion of American Journal of Clinical Oncology • Volume XX, Number X, XXX 2010 www.amjclinicaloncology.com | 1
  2. 2. Chen and Mou American Journal of Clinical Oncology • Volume XX, Number X, XXX 2010 20 mg scopolamine butylbromide, each patient drank 800 mL or predictors accompanied by their regression coefficients. The more water. An unenhanced scan was done to evaluate gastric calibration of the model, that described agreement between expected distention. The enhanced scan was obtained following intravenous and actually observed outcomes, was measured by the Hosmer- injection of 100 mL nonionic iodinated contrast at a rate of 3 mL/s. Lemeshow goodness-of-fit test.21 A P value of less than 0.05 was On CT images, the gastric wall was considered thickened considered statistically significant. when it exceeded 3 mm in the antrum, 5 mm in the body, and 7 mm Based on the multiple logistic model, an easy-to-use risk in the fundus.9 The depth of tumor invasion visualized by CT was score was created. A partial score was computed for each indepen- classified as follows: (1) T0, no evidence of alteration of the gastric dent variable according to the relative weight of significance in the wall with a normal fat plane; (2) T1, focal thickening of the inner multivariate analysis. The regression coefficients pertinent to the layer with a visible outer layer of the gastric wall and a clear fat variables retained in the final model were divided by the smallest plane surrounding the tumor; (3) T2, focal or diffuse thickening of regression coefficient, and the results were rounded to the nearest the gastric wall with transmural involvement and a smooth outer integer.22 The sum of partial scores produced the overall risk score border of the wall or only a few small linear strands of soft tissue for individual patients. Receiver operating characteristic (ROC) extending into the fat plane involving less than one-third of the tumor extent; (4) T3, transmural tumors with obvious blurring of at least one-third of the tumor extent or wide reticular strands sur- rounding the outer border of the tumor; (5) T4, obliteration of fat TABLE 1. Relationship Between pTNM Stages and plane between the gastric tumor and an adjacent organ or invasion of Clinicopathological Features in 108 Patients With Gastric an adjacent organ.15 Cancer (Univariate Analysis) Lymph nodes were considered to be metastatic if they were Stage Stage larger than 10 mm in diameter.16 N1 was defined as enlarged Variables I/II III/IV P perigastric lymph nodes within 3 cm of the primary lesion. N2 was Age (yr) NS* defined as enlarged lymph nodes more than 3 cm from the primary lesion, including those located along the left gastric, common 60 28 (50.0) 27 (49.1) hepatic, splenic or celiac arteries.15 Two experienced abdominal 60 26 (49.1) 27 (50.9) radiologists, who were blinded to endoscopic findings, indepen- Gender NS dently read CT images. Disagreements between readers were re- Male 41 (55.4) 33 (44.6) solved through consensus. Female 13 (38.2) 21 (61.8) Tumor location NS Preoperative Laboratory Tests Low 28 (46.7) 32 (53.3) Hemoglobin concentration, platelet count, and serum albumin Middle 20 (58.8) 14 (41.2) values were examined in early morning samples taken before break- Upper 5 (50.0) 5 (50.0) fast on the second day after admission and immediately measured by Two-third or more 1 (25.0) 3 (75.0) an Auto-Analyzer method.17 Anemia, thrombocytosis, and hy- poalbuminaemia were defined as hemoglobin level less than 12.0 Tumor size P 0.05 g/dL, platelet count more than 40 ( 104/ L), and serum albumin 2.0 cm 26 (89.7) 3 (10.3) concentration less than 3.5 g/dL, respectively.18 –20 2.1–4.0 cm 16 (57.1) 12 (42.9) 4.1–6.0 cm 9 (26.5) 25 (73.5) Surgery 6.0 cm 3 (17.6) 14 (82.4) The following standardized operative procedures were per- T category (on CT scans) P 0.05 formed: (1) total or subtotal gastrectomy was performed, depending T0/1 87 (84.5) 1 (1.0) on the location and macroscopic type of gastric cancer; and (2) T2 56 (35.7) 27 (17.2) extended D2 lymphadenectomy was performed according to the T3 20 (9.8) 71 (34.6) rules established by the Japanese Research Society for Gastric Cancer.14 Perigastric lymph nodes (No. 1– 6) and nodes along the T4 1 (14.3) 3 (42.9) left gastric artery (No. 7), along the common hepatic artery (No. 8), N category (on CT scans) P 0.05 around the celiac axis (No. 9), and along the splenic artery (No. 11) N0 37 (75.5) 12 (24.5) were resected routinely. Lymph nodes in the hepatoduodenal liga- N1 13 (43.3) 17 (56.7) ment (No. 12a) and along the superior mesenteric vein (No. 14v) N2 4 (13.8) 25 (86.2) were resected when the primary lesion was located in the lower third Histological type P 0.05 of the stomach. Lymph nodes at the splenic hilum (No. 10) were Differentiated 23 (67.6) 11 (32.4) resected with the spleen when total or proximal gastrectomy was Undifferentiated 31 (41.9) 43 (58.1) performed. A median of 26 lymph nodes (range, 15– 60 nodes) were Anemia P 0.05 retrieved for histologic examination. No 38 (65.5) 20 (34.5) Statistical Analysis Yes 16 (32.0) 34 (68.0) All statistical calculations were carried out using Statistical Thrombocytosis NS Package for the Social Sciences 10.0 for Windows (Chicago, IL). No 41 (47.7) 45 (52.3) Univariate analysis was employed to investigate whether imaging Yes 13 (59.1) 9 (40.9) and clinicopathological parameters correlated with tumor stages. On Hypoalbuminaemia P 0.05 multivariate analysis, a stepwise logistic regression model was No 52 (55.9) 41 (44.1) adopted to identify independent predictive factors for tumor stages, Yes 2 (13.2) 13 (86.7) in which the pTNM stage was chosen as a dependent variable and significant risk factors selected by univariate analysis were chosen Values in the parenthesis are percentages. *NS indicates not significant. as covariates. The final model generated a set of independent 2 | www.amjclinicaloncology.com © 2010 Lippincott Williams & Wilkins
  3. 3. American Journal of Clinical Oncology • Volume XX, Number X, XXX 2010 A Score to Predict TNM Stages analysis was used to define a cut point of the risk score for optimal sensitivity and specificity in the prediction of stage III/IV.23 The TABLE 3. A Risk Score System for Patients With Gastric optimal cut point was selected on the basis of Youden’s index (J), Cancer which was calculated using the equation: J sensitivity speci- Variables Partial Score ficity 1.24 The area under the ROC curve (AUC) reflected the T category (on CT scans) ability of our score to discriminate patients with stage III/IV disease T0/1 0 from those with stage I/II disease.25 T2 2 RESULTS T3 4 T4 5 Univariate Analysis of the Relationship Between N category (on CT scans) pTNM Stages and Clinicopathological Parameters N0 0 Table 1 lists the clinicopathological characteristics of 108 N1 2 patients with gastric cancer. Histopathologically, there were 28 N2 3 (25.9%) cases in stage I, 26 (24.1%) in stage II, 39 (36.1%) in stage III, Tumor size and 15 (13.9%) in stage IV. The helical CT detected 94.4% (102/108) 2.0 cm 0 of the primary tumors. All 6 cases missed by helical CT were pT1 2.1–4.0 cm 1 disease. Univariate analysis demonstrated that CT category, estimated tumor nodes (CN) category, tumor size, histologic differentiation, 4.1–6.0 cm 2 anemia and hypoalbuminaemia had a significant association with 6.0 cm 3 pTNM stages (Table 1). Hypoalbuminaemia No 0 Multivariate Analysis of Predictive Factors for Yes 2 Tumor Stages The 6 significant variables identified by univariate analysis were included in a stepwise logistic regression model. The final model revealed that CT category, CN category, tumor size and hypoalbuminaemia were independent predictors of stage III/IV; the corresponding regression coefficients, standard error (SE) of the coefficients and P values were presented in Table 2. The Hosmer- Lemeshow goodness-of-fit test was performed to assess the calibra- tion of the logistic regression model. The Hosmer-Lemeshow sta- tistic indicated a good fit of the final model (P 0.751). Computation of the Score The risk score was established on the basis of the 4 variables retained in the final model. As shown in Table 3, a numerical score was designated for each independent variable. The total score of a given patient was obtained by adding his appropriate partial scores. The mean SE value of the overall risk score was 5.7 (0.3) (range, TABLE 2. Multivariate Analysis of Factors Related to pTNM Stages Independent Factors SE ( ) P T category (on CT scans) P 0.05 T0/1 T2 2.175 1.556 T3 3.670 1.572 T4 5.132 2.060 N category (on CT scans) P 0.05 N0 FIGURE 1. The ROC curve for our risk score’s prediction of stage III/IV. N1 1.541 0.714 N2 2.626 0.818 Tumor size P 0.05 0 –13). When patients were stratified by pTNM stages, the mean SE 2.0 cm score values were 1.8 (0.4) in stage I, 5.3 (0.4) in stage II, 7.6 (0.3) 2.1–4.0 cm 0.969 0.907 in stage III, and 9.1 (0.6) in stage IV. 4.1–6.0 cm 1.775 0.921 Using ROC analysis, a cut point at 7 was found to be 6.0 cm 3.264 1.344 associated with optimal sensitivity and specificity of 79.6% and Hypoalbuminaemia P 0.05 85.2%, respectively, in the prediction of stage III/IV. The discrim- No inative ability of our score was good (stage III/IV vs. stage I/II, AUC Yes 2.344 1.113 0.861– 0.965; Fig. 1). If the total score was less than 7, the patient was classified as stage I/II; whether it was equal to or greater than 7, © 2010 Lippincott Williams & Wilkins www.amjclinicaloncology.com | 3
  4. 4. Chen and Mou American Journal of Clinical Oncology • Volume XX, Number X, XXX 2010 the patient was classified as stage III/IV. Accordingly, 57 cases REFERENCES (52.8%) were regarded in stage I/II and 51 (47.2%) in stage III/IV. 1. Boring CC, Squires TS, Tong T, et al. Cancer statistics, 1994. CA Cancer We compared predictions from the risk score with postoperative J Clin. 1994;44:7–26. pTNM stages. The overall accuracy was 82.4%. 2. Wanebo HJ, Kennedy BJ, Chmiel J, et al. Cancer of the stomach. A patient care study by the American College of Surgeons. Ann Surg. 1993;218:583– 592. 3. Kim JP. Surgical results in gastric cancer. Semin Surg Oncol. 1999;17:132– DISCUSSION 138. So far, scoring systems have been frequently used to predict 4. Crookes P, Leichman CG, Leichman L, et al. 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