Construction of prognostic risk model in patients with pancreatic malignancy_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

 CHENG Bin ¹ , JIANG Zhenhui ¹ , CHEN Xiaopeng ² , CHEN Zhenyuan ¹ , HU Xiaochuan ¹ , WU Wenming ¹

1. Department of Hepatobiliary Surgery, Huangshan People’s Hospital, Huangshan, Anhui 245000, P. R. China;
2. Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wannan Medical College, Wuhu, Anhui 241001, P. R. China;

Corresponding author：

CHENG Bin, Email: chengb1991@163.com

Keywords：

pancreatic malignancy; prediction model; Surveillance, Epidemiology, and End Results Database; prognosis

DOI：

10.7507/1007-9424.202003083

Video：

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Objective To construct a model for predicting prognosis risk in patients with pancreatic malignancy (PM).Methods The clinicopathological data of 8 763 patients with PM undergone resection between 2010 and 2015 were collected and analyzed by SEER*Stat (v8.3.5) and R software, respectively. The univariate and multivariate Cox proportional hazard regression analysis were used to analyze the factors for predicting prognosis outcome risk and constructed the nomograms of patients with PM, respectively. Kaplan-Meier method was used to evaluate the survival of patients according to relevant factors and the high risk group and low risk group of patients with PM. The discriminative ability and calibration of the nomograms to predict overall survival were tested by using C-index, area under ROC curve (AUC) and calibration plots.Results The multivariate Cox proportional hazard regression analysis showed that age, T staging, N staging, M staging, histological type, the differentiation, number of regional lymph node dissection, chemotherapy, and radiotherapy were independent factors for predicting the prognosis of patients with PM (P<0.05). Based on regression analysis of patients with PM, a nomograms model for predicting the risk of patients with PM was established, including age, T staging, N staging, M staging, histological type, the differentiation, tumor location, type of surgery, number of regional lymph node dissection, chemotherapy, and radiotherapy. The discriminative ability and calibration of the nomograms revealed good predictive ability as indicated by the C-index (0.747 for modeling group and 0.734 for verification group). The 3- and 5-year survival AUC values of the modeling group were 0.766 and 0.781, and the validation group were 0.758 and 0.783, respectively. The calibration plots showed that predictive value of the 3- and 5-year survival were close to the actual values in both modeling group and the verification group. Conclusions Independent predictors of survival risk after curative-intent surgery for PM were selected to create nomograms for predicting overall survival. The nomograms provide a basis for judging the prognosis of PM patients.

Citation： CHENG Bin, JIANG Zhenhui, CHEN Xiaopeng, CHEN Zhenyuan, HU Xiaochuan, WU Wenming. Construction of prognostic risk model in patients with pancreatic malignancy. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2020, 27(12): 1506-1514. doi: 10.7507/1007-9424.202003083 Copy

1.	Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2018, 68(6): 394-424.
2.	Tempero MA, Malafa MP, Chiorean EG, et al. Pancreatic adenocarcinoma, version 1.2019. J Natl Compr Canc Netw, 2019, 17(3): 202-210.
3.	Sajjad M, Batra S, Hoffe S, et al. Use of radiation therapy in locally advanced pancreatic cancer improves survival: a SEER database analysis. Am J Clin Oncol, 2018, 41(3): 236-241.
4.	Nayar P, Chandak A, Gupta N, et al. Postoperative mortality following multi-modality therapy for pancreatic cancer: analysis of the SEER-medicare data. J Surg Oncol, 2017, 115(2): 158-163.
5.	Edge SB, Byrd DR, Compton CC, et al. AJCC Cancer Staging Manual. 7th Edition. Springer, 2010: 241-249.
6.	Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin, 2018, 68(1): 7-30.
7.	Brecht IB, Schneider DT, Klöppel G, et al. Malignant pancreatic tumors in children and young adults: evaluation of 228 patients identified through the Surveillance, Epidemiology, and End Result (SEER) database. Klin Padiatr, 2011, 223(6): 341-345.
8.	Li X, Liu Z, Ye Z, et al. Impact of age on survival of patients with pancreatic cancer after surgery: analysis of SEER data. Pancreatology, 2018, 18(1): 133-138.
9.	张灵敏, 路宁, 袁慧, 等. 影响胰腺癌特异性生存率的相关因素分析. 山西医科大学学报, 2019, 50(11): 1531-1537.
10.	张群华, 倪泉兴. 胰腺癌 2 340 例临床病例分析. 中华医学杂志, 2004, 84(3): 214-218.
11.	Sun H, Ma H, Hong G, et al. Survival improvement in patients with pancreatic cancer by decade: a period analysis of the SEER database, 1981-2010. Sci Rep, 2014, 4: 6747.
12.	Arnold LD, Patel AV, Yan Y, et al. Are racial disparities in pancreatic cancer explained by smoking and overweight/obesity? Cancer Epidemiol Biomarkers Prev, 2009, 18(9): 2397-2405.
13.	Cheung R. Racial and social economic factors impact on the cause specific survival of pancreatic cancer: a SEER survey. Asian Pac J Cancer Prev, 2013, 14(1): 159-163.
14.	沈璟, 高绥之, 王欢, 等. 四种驱动基因突变状态对根治性切除胰腺癌患者预后的评估价值. 中华外科杂志, 2019, 57(11): 840-847.
15.	Sy MS, Altekruse SF, Li C, et al. Association of prion protein expression with pancreatic adenocarcinoma survival in the SEER residual tissue repository. Cancer Biomark, 2011-2012, 10(6): 251-258.
16.	Mishra NK, Guda C. Genome-wide DNA methylation analysis reveals molecular subtypes of pancreatic cancer. Oncotarget, 2017, 8(17): 28990-29012.
17.	Vick AD, Hery DN, Markowiak SF, et al. Closing the disparity in pancreatic cancer outcomes: a closer look at nonmodifiable factors and their potential use in treatment. Pancreas, 2019, 48(2): 242-249.
18.	Yamamoto T, Yagi S, Kinoshita H, et al. Long-term survival after resection of pancreatic cancer: a single-center retrospective analysis. World J Gastroenterol, 2015, 21(1): 262-268.
19.	胡伟, 张桢, 沈丰. Cox 比例风险模型分析胰腺癌手术预后相关影响因素. 湖北医药学院学报, 2018, 37(2): 144-147.
20.	沈红, 汪秀云, 许辉琼, 等. 274 例胰腺癌临床病理特征及影响患者预后的危险因素. 昆明医科大学学报, 2019, 40(3): 97-101.
21.	Dima SO, Dumitrascu T, Pechianu C, et al. Prognostic factors in patients with surgical resection of pancreatic neuroendocrine tumours. Acta Endocrinol (Buchar), 2018, 14(3): 389-393.
22.	Nipp RD, Zanconato A, Zheng H, et al. Predictors of early mortality after surgical resection of pancreatic adenocarcinoma in the era of neoadjuvant treatment. Pancreas, 2017, 46(2): 183-189.
23.	Furukawa K, Shiba H, Hamura R, et al. Prognostic factors in patients with recurrent pancreatic cancer: a multicenter database analysis. Anticancer Res, 2020, 40(1): 293-298.
24.	Ivanics T, Bergquist JR, Shubert CR, et al. Small cell carcinoma of the pancreas: a surgical disease. Pancreas, 2016, 45(10): 1461-1466.
25.	Lloyd RV, Osamura RY, Klöppel G, et al. WHO Classification of Tumours of Endocrine Organs. 4th Edition. IARC, 2017: 209-239.
26.	Mukhija D, Nagpal SJS, Sohal DPS. Epidemiology, tumor characteristics, and survival in patients with primary pancreatic lymphoma: a large population-based study using the SEER database. Am J Clin Oncol, 2019, 42(5): 454-458.
27.	冉东辉, 娄子彦, 耿诚, 等. 胰头区恶性肿瘤术后预后因素的研究进展. 中国普外基础与临床杂志, 2020, 27(5): 646-652.
28.	Amin MB, Edge S, Greene F, et al. AJCC cancer staging manual. Springer, 2017: 337-347.
29.	白燕南, 严茂林. 胰腺癌综合诊治指南 (2018 版) 外科相关部分解读. 中国普外基础与临床杂志, 2018, 25(6): 669-672.
30.	Artinyan A, Soriano PA, Prendergast C, et al. The anatomic location of pancreatic cancer is a prognostic factor for survival. HPB (Oxford), 2008, 10(5): 371-376.
31.	Lau MK, Davila JA, Shaib YH. Incidence and survival of pancreatic head and body and tail cancers: a population-based study in the United States. Pancreas, 2010, 39(4): 458-462.
32.	Winer LK, Dhar VK, Wima K, et al. The impact of tumor location on resection and survival for pancreatic ductal adenocarcinoma. J Surg Res, 2019, 239: 60-66.
33.	Yin L, Xiao L, Gao Y, et al. Comparative bioinformatical analysis of pancreatic head cancer and pancreatic body/tail cancer. Med Oncol, 2020, 37(5): 46.
34.	Mirkin KA, Hollenbeak CS, Wong J. Greater lymph node retrieval and lymph node ratio impacts survival in resected pancreatic cancer. J Surg Res, 2017, 220: 12-24.
35.	Oettle H, Post S, Neuhaus P, et al. Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial. JAMA, 2007, 297(3): 267-277.
36.	Rao AD, Sugar EA, Chang DT, et al. Patient-reported outcomes of a multicenter phase 2 study investigating gemcitabine and stereotactic body radiation therapy in locally advanced pancreatic cancer. Pract Radiat Oncol, 2016, 6(6): 417-424.
37.	虞先濬, 刘亮, 徐华祥, 等. 胰腺癌综合诊治指南 (2018 版). 临床肝胆病杂志, 2018, 34(10): 2109-2120.
38.	Tempero MA, Malafa MP, Al-Hawary M, et al. Pancreatic Adenocarcinoma, Version 2.2017, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw, 2017, 15(8): 1028-1061.
39.	Yamaguchi K, Okusaka T, Shimizu K, et al. Clinical practice guidelines for pancreatic cancer 2016 from the Japan pancreas society: a synopsis. Pancreas, 2017, 46(5): 595-604.
40.	Barnes CA, Chavez MI, Tsai S, et al. Survival of patients with borderline resectable pancreatic cancer who received neoadjuvant therapy and surgery. Surgery, 2019, 166(3): 277-285.
41.	Khorana AA, Mangu PB, Katz MHG. Potentially curable pancreatic cancer: American Society of Clinical Oncology Clinical Practice Guideline Update Summary. J Oncol Pract, 2017, 13(6): 388-391.

1. Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2018, 68(6): 394-424.
2. Tempero MA, Malafa MP, Chiorean EG, et al. Pancreatic adenocarcinoma, version 1.2019. J Natl Compr Canc Netw, 2019, 17(3): 202-210.
3. Sajjad M, Batra S, Hoffe S, et al. Use of radiation therapy in locally advanced pancreatic cancer improves survival: a SEER database analysis. Am J Clin Oncol, 2018, 41(3): 236-241.
4. Nayar P, Chandak A, Gupta N, et al. Postoperative mortality following multi-modality therapy for pancreatic cancer: analysis of the SEER-medicare data. J Surg Oncol, 2017, 115(2): 158-163.
5. Edge SB, Byrd DR, Compton CC, et al. AJCC Cancer Staging Manual. 7th Edition. Springer, 2010: 241-249.
6. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin, 2018, 68(1): 7-30.
7. Brecht IB, Schneider DT, Klöppel G, et al. Malignant pancreatic tumors in children and young adults: evaluation of 228 patients identified through the Surveillance, Epidemiology, and End Result (SEER) database. Klin Padiatr, 2011, 223(6): 341-345.
8. Li X, Liu Z, Ye Z, et al. Impact of age on survival of patients with pancreatic cancer after surgery: analysis of SEER data. Pancreatology, 2018, 18(1): 133-138.
9. 张灵敏, 路宁, 袁慧, 等. 影响胰腺癌特异性生存率的相关因素分析. 山西医科大学学报, 2019, 50(11): 1531-1537.
10. 张群华, 倪泉兴. 胰腺癌 2 340 例临床病例分析. 中华医学杂志, 2004, 84(3): 214-218.
11. Sun H, Ma H, Hong G, et al. Survival improvement in patients with pancreatic cancer by decade: a period analysis of the SEER database, 1981-2010. Sci Rep, 2014, 4: 6747.
12. Arnold LD, Patel AV, Yan Y, et al. Are racial disparities in pancreatic cancer explained by smoking and overweight/obesity? Cancer Epidemiol Biomarkers Prev, 2009, 18(9): 2397-2405.
13. Cheung R. Racial and social economic factors impact on the cause specific survival of pancreatic cancer: a SEER survey. Asian Pac J Cancer Prev, 2013, 14(1): 159-163.
14. 沈璟, 高绥之, 王欢, 等. 四种驱动基因突变状态对根治性切除胰腺癌患者预后的评估价值. 中华外科杂志, 2019, 57(11): 840-847.
15. Sy MS, Altekruse SF, Li C, et al. Association of prion protein expression with pancreatic adenocarcinoma survival in the SEER residual tissue repository. Cancer Biomark, 2011-2012, 10(6): 251-258.
16. Mishra NK, Guda C. Genome-wide DNA methylation analysis reveals molecular subtypes of pancreatic cancer. Oncotarget, 2017, 8(17): 28990-29012.
17. Vick AD, Hery DN, Markowiak SF, et al. Closing the disparity in pancreatic cancer outcomes: a closer look at nonmodifiable factors and their potential use in treatment. Pancreas, 2019, 48(2): 242-249.
18. Yamamoto T, Yagi S, Kinoshita H, et al. Long-term survival after resection of pancreatic cancer: a single-center retrospective analysis. World J Gastroenterol, 2015, 21(1): 262-268.
19. 胡伟, 张桢, 沈丰. Cox 比例风险模型分析胰腺癌手术预后相关影响因素. 湖北医药学院学报, 2018, 37(2): 144-147.
20. 沈红, 汪秀云, 许辉琼, 等. 274 例胰腺癌临床病理特征及影响患者预后的危险因素. 昆明医科大学学报, 2019, 40(3): 97-101.
21. Dima SO, Dumitrascu T, Pechianu C, et al. Prognostic factors in patients with surgical resection of pancreatic neuroendocrine tumours. Acta Endocrinol (Buchar), 2018, 14(3): 389-393.
22. Nipp RD, Zanconato A, Zheng H, et al. Predictors of early mortality after surgical resection of pancreatic adenocarcinoma in the era of neoadjuvant treatment. Pancreas, 2017, 46(2): 183-189.
23. Furukawa K, Shiba H, Hamura R, et al. Prognostic factors in patients with recurrent pancreatic cancer: a multicenter database analysis. Anticancer Res, 2020, 40(1): 293-298.
24. Ivanics T, Bergquist JR, Shubert CR, et al. Small cell carcinoma of the pancreas: a surgical disease. Pancreas, 2016, 45(10): 1461-1466.
25. Lloyd RV, Osamura RY, Klöppel G, et al. WHO Classification of Tumours of Endocrine Organs. 4th Edition. IARC, 2017: 209-239.
26. Mukhija D, Nagpal SJS, Sohal DPS. Epidemiology, tumor characteristics, and survival in patients with primary pancreatic lymphoma: a large population-based study using the SEER database. Am J Clin Oncol, 2019, 42(5): 454-458.
27. 冉东辉, 娄子彦, 耿诚, 等. 胰头区恶性肿瘤术后预后因素的研究进展. 中国普外基础与临床杂志, 2020, 27(5): 646-652.
28. Amin MB, Edge S, Greene F, et al. AJCC cancer staging manual. Springer, 2017: 337-347.
29. 白燕南, 严茂林. 胰腺癌综合诊治指南 (2018 版) 外科相关部分解读. 中国普外基础与临床杂志, 2018, 25(6): 669-672.
30. Artinyan A, Soriano PA, Prendergast C, et al. The anatomic location of pancreatic cancer is a prognostic factor for survival. HPB (Oxford), 2008, 10(5): 371-376.
31. Lau MK, Davila JA, Shaib YH. Incidence and survival of pancreatic head and body and tail cancers: a population-based study in the United States. Pancreas, 2010, 39(4): 458-462.
32. Winer LK, Dhar VK, Wima K, et al. The impact of tumor location on resection and survival for pancreatic ductal adenocarcinoma. J Surg Res, 2019, 239: 60-66.
33. Yin L, Xiao L, Gao Y, et al. Comparative bioinformatical analysis of pancreatic head cancer and pancreatic body/tail cancer. Med Oncol, 2020, 37(5): 46.
34. Mirkin KA, Hollenbeak CS, Wong J. Greater lymph node retrieval and lymph node ratio impacts survival in resected pancreatic cancer. J Surg Res, 2017, 220: 12-24.
35. Oettle H, Post S, Neuhaus P, et al. Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial. JAMA, 2007, 297(3): 267-277.
36. Rao AD, Sugar EA, Chang DT, et al. Patient-reported outcomes of a multicenter phase 2 study investigating gemcitabine and stereotactic body radiation therapy in locally advanced pancreatic cancer. Pract Radiat Oncol, 2016, 6(6): 417-424.
37. 虞先濬, 刘亮, 徐华祥, 等. 胰腺癌综合诊治指南 (2018 版). 临床肝胆病杂志, 2018, 34(10): 2109-2120.
38. Tempero MA, Malafa MP, Al-Hawary M, et al. Pancreatic Adenocarcinoma, Version 2.2017, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw, 2017, 15(8): 1028-1061.
39. Yamaguchi K, Okusaka T, Shimizu K, et al. Clinical practice guidelines for pancreatic cancer 2016 from the Japan pancreas society: a synopsis. Pancreas, 2017, 46(5): 595-604.
40. Barnes CA, Chavez MI, Tsai S, et al. Survival of patients with borderline resectable pancreatic cancer who received neoadjuvant therapy and surgery. Surgery, 2019, 166(3): 277-285.
41. Khorana AA, Mangu PB, Katz MHG. Potentially curable pancreatic cancer: American Society of Clinical Oncology Clinical Practice Guideline Update Summary. J Oncol Pract, 2017, 13(6): 388-391.

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Construction of prognostic risk model in patients with pancreatic malignancy

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