High CFP score indicates poor prognosis and chemoradiotherapy response in LARC patients

Cancer Cell International - Tập 21 - Trang 1-11 - 2021
Siyi Lu1, Zhenzhen Liu1, Bingyan Wang1, Fei Li1, Yan Meng1, Junwei Wang1, Yuxia Wang2, Hao Wang2, Xin Zhou1, Wei Fu1
1Department of General Surgery, Peking University Third Hospital, Beijing, China
2Department of Radiotherapy, Peking University Third Hospital, Beijing, China

Tóm tắt

Preoperative tumor markers, inflammation, and nutritional status are considered important predictors of prognosis and tumor response in locally advanced rectal cancer (LARC) patients. This study aims to explore the prognostic and predictive role of carcinoembryonic antigen (CEA), the Fibrinogen-Albumin Ratio Index (FARI), the Prognostic Nutritional Index (PNI) in LARC patients and compared them with a novel combined CEA-FARI-PNI (CFP) scoring system. A total of 138 LARC patients undergoing radical surgery following neoadjuvant chemoradiotherapy (NCRT) between January 2012 and March 2019 were enrolled. The X-tile program was used to determine the optimal cut-off values of CEA, FARI, and PNI, and CFP scoring system was constructed accordingly. The prognostic ability of these factors was assessed by the time-dependent receiver operating characteristic (ROC) curve, Kaplan–Meier, Cox regression, and logistic regression. Nomogram was established to evaluate the predictive role of these factors in tumor response. The optimal cut-off values of CEA, FARI, and PNI were 5.15 ng/l, 10.56%, and 42.25 g/L, respectively. The time-dependent ROC curve showed that compared to CEA, FARI, and PNI, CFP showed stable predictive efficacy for overall survival (OS) and disease-free survival (DFS). In multivariate analysis, CFP was the only factor that could independently predict OS (HR = 8.117, p = 0.001) and DFS (HR = 4.994, p < 0.001). Moreover, high CFP (OR = 3.693, p = 0.002) was also an independent risk factor of poor response. The area under the ROC curve (AUC) of the nomograms for predicting tumor response was better including CFP (0.717) than without CFP (0.656) (p < 0.05). The CFP score was a more reliable marker for predicting OS, DFS, and NCRT efficacy in LARC patients, and the score could apparently improve predicted efficacy of the nomogram.

Tài liệu tham khảo

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. https://doi.org/10.3322/caac.21492. Siegel RL, Miller KD, Goding Sauer A, et al. Colorectal cancer statistics, 2020. CA Cancer J Clin. 2020;70(3):145–64. https://doi.org/10.3322/caac.21601. Collette L, Bosset JF, den Dulk M, et al. Patients with curative resection of cT3-4 rectal cancer after preoperative radiotherapy or radiochemotherapy: does anybody benefit from adjuvant fluorouracil-based chemotherapy? A trial of the European Organisation for Research and Treatment of Cancer Radiation Oncology Group. J Clin Oncol. 2007;25(28):4379–86. https://doi.org/10.1200/JCO.2007.11.9685. Fleshman J, Branda ME, Sargent DJ, et al. Disease-free survival and local recurrence for laparoscopic resection compared with open resection of stage ii to iii rectal cancer: follow-up results of the ACOSOG Z6051 randomized controlled trial. Ann Surg. 2019;269(4):589–95. https://doi.org/10.1097/SLA.0000000000003002. Voss RK, Lin JC, Roper MT, et al. Adjuvant chemotherapy does not improve recurrence-free survival in patients with stage 2 or stage 3 rectal cancer after neoadjuvant chemoradiotherapy and total mesorectal excision. Dis Colon Rectum. 2020;63(4):427–40. https://doi.org/10.1097/DCR.0000000000001558. Nakamura Y, Shida D, Tanabe T, et al. Prognostic impact of preoperatively elevated and postoperatively normalized carcinoembryonic antigen levels following curative resection of stage I-III rectal cancer. Cancer Med. 2020;9(2):653–62. https://doi.org/10.1002/cam4.2758. Perez RO, Sao Juliao GP, Habr-Gama A, et al. The role of carcinoembriogenic antigen in predicting response and survival to neoadjuvant chemoradiotherapy for distal rectal cancer. Dis Colon Rectum. 2009;52(6):1137–43. https://doi.org/10.1007/DCR.0b013e31819ef76b. Jang NY, Kang SB, Kim DW, et al. The role of carcinoembryonic antigen after neoadjuvant chemoradiotherapy in patients with rectal cancer. Dis Colon Rectum. 2011;54(2):245–52. https://doi.org/10.1007/DCR.0b013e3181fcee68. Candido J, Hagemann T. Cancer-related inflammation. J Clin Immunol. 2013;33(Suppl 1):S79-84. https://doi.org/10.1007/s10875-012-9847-0. Kuipers EJ, Grady WM, Lieberman D, et al. Colorectal cancer. Nat Rev Dis Primers. 2015;1:15065. https://doi.org/10.1038/nrdp.2015.65. Shawki S, Ashburn J, Signs SA, et al. Colon cancer: inflammation-associated cancer. Surg Oncol Clin N Am. 2018;27(2):269–87. https://doi.org/10.1016/j.soc.2017.11.003. Mantovani A, Allavena P, Sica A, et al. Cancer-related inflammation. Nature. 2008;454(7203):436–44. https://doi.org/10.1038/nature07205. Dreyer SB, Powell AG, McSorley ST, et al. The pretreatment systemic inflammatory response is an important determinant of poor pathologic response for patients undergoing neoadjuvant therapy for rectal cancer. Ann Surg Oncol. 2017;24(5):1295–303. https://doi.org/10.1245/s10434-016-5684-3. Chandra RK. Nutrition and the immune system: an introduction. Am J Clin Nutr. 1997;66(2):460S-S463. https://doi.org/10.1093/ajcn/66.2.460S. Jager-Wittenaar H, Dijkstra PU, Vissink A, et al. Malnutrition and quality of life in patients treated for oral or oropharyngeal cancer. Head Neck. 2011;33(4):490–6. https://doi.org/10.1002/hed.21473. Chen QG, Zhang L, Sun F, et al. Elevated FPR confers to radiochemoresistance and predicts clinical efficacy and outcome of metastatic colorectal cancer patients. Aging (Albany NY). 2019;11(6):1716–32. https://doi.org/10.18632/aging.101864. Wang YY, Liu ZZ, Xu D, et al. Fibrinogen-Albumin Ratio Index (FARI): a more promising inflammation-based prognostic marker for patients undergoing hepatectomy for colorectal liver metastases. Ann Surg Oncol. 2019;26(11):3682–92. https://doi.org/10.1245/s10434-019-07586-3. Tan Z, Zhang M, Han Q, et al. A novel blood tool of cancer prognosis in esophageal squamous cell carcinoma: the Fibrinogen/Albumin Ratio. J Cancer. 2017;8(6):1025–9. https://doi.org/10.7150/jca.16491. Zhang J, Ruan J, Wang W, et al. Prognostic value of the combination of CEA and fibrinogen/albumin ratio in resectable gastric cancer. Cancer Manag Res. 2020;12:2767–75. https://doi.org/10.2147/CMAR.S246566. Lu S, Liu Z, Zhou X, et al. Preoperative Fibrinogen-Albumin Ratio Index (FARI) is a reliable prognosis and chemoradiotherapy sensitivity predictor in locally advanced rectal cancer patients undergoing radical surgery following neoadjuvant chemoradiotherapy. Cancer Manag Res. 2020;12:8555–68. https://doi.org/10.2147/CMAR.S273065. Okugawa Y, Toiyama Y, Oki S, et al. Feasibility of assessing prognostic nutrition index in patients with rectal cancer who receive preoperative chemoradiotherapy. JPEN J Parenter Enteral Nutr. 2018;42(6):998–1007. https://doi.org/10.1002/jpen.1041. Goto W, Kashiwagi S, Asano Y, et al. Predictive value of lymphocyte-to-monocyte ratio in the preoperative setting for progression of patients with breast cancer. BMC Cancer. 2018;18(1):1137. https://doi.org/10.1186/s12885-018-5051-9. Yang L, He W, Kong P, et al. Clinical baseline and prognostic difference of platelet lymphocyte ratio (PLR) in right-sided and let-sided colon cancers. BMC Cancer. 2017;17(1):873. https://doi.org/10.1186/s12885-017-3862-8. Chen JH, Zhai ET, Yuan YJ, et al. Systemic immune-inflammation index for predicting prognosis of colorectal cancer. World J Gastroenterol. 2017;23(34):6261–72. https://doi.org/10.3748/wjg.v23.i34.6261. El Sissy C, Kirilovsky A, Van den Eynde M, et al. A diagnostic biopsy-adapted immunoscore predicts response to neoadjuvant treatment and selects patients with rectal cancer eligible for a watch-and-wait strategy. Clin Cancer Res. 2020;26(19):5198–207. https://doi.org/10.1158/1078-0432.CCR-20-0337. Shu YJ, Weng H, Bao RF, et al. Clinical and prognostic significance of preoperative plasma hyperfibrinogenemia in gallbladder cancer patients following surgical resection: a retrospective and in vitro study. BMC Cancer. 2014;14:566. https://doi.org/10.1186/1471-2407-14-566. Gupta D, Lis CG. Pretreatment serum albumin as a predictor of cancer survival: a systematic review of the epidemiological literature. Nutr J. 2010;9:69. https://doi.org/10.1186/1475-2891-9-69. Lang-Schwarz C, Melcher B, Haumaier F, et al. Budding and tumor-infiltrating lymphocytes - combination of both parameters predicts survival in colorectal cancer and leads to new prognostic subgroups. Hum Pathol. 2018;79:160–7. https://doi.org/10.1016/j.humpath.2018.05.010. Zinczuk J, Maciejczyk M, Zareba K, et al. Antioxidant barrier, redox status, and oxidative damage to biomolecules in patients with colorectal cancer. Can malondialdehyde and catalase be markers of colorectal cancer advancement? Biomolecules. 2019. https://doi.org/10.3390/biom9100637. Zinczuk J, Maciejczyk M, Zareba K, et al. Pro-oxidant enzymes, redox balance and oxidative damage to proteins, lipids and DNA in colorectal cancer tissue. Is oxidative stress dependent on tumour budding and inflammatory infiltration? Cancers. 2020. https://doi.org/10.3390/cancers12061636. Agsalda-Garcia M, Shieh T, Souza R, et al. Raman-Enhanced Spectroscopy (RESpect) probe for childhood non-hodgkin lymphoma. Sci Med J. 2020;2(1):1–7. https://doi.org/10.28991/SciMedJ-2020-0201-1. Kosvyra A, Maramis C, Chouvarda I. Developing an integrated genomic profile for cancer patients with the use of NGS data. Emerg Sci J. 2019;3(3):157–67. https://doi.org/10.28991/esj-2019-01178. Mandard AM, Dalibard F, Mandard JC, et al. Pathologic assessment of tumor regression after preoperative chemoradiotherapy of esophageal carcinoma. Clinicopathol Correlat Cancer. 1994;73(11):2680–6. https://doi.org/10.1002/1097-0142(19940601)73:11%3c2680::aid-cncr2820731105%3e3.0.co;2-c. Quah HM, Chou JF, Gonen M, et al. Pathologic stage is most prognostic of disease-free survival in locally advanced rectal cancer patients after preoperative chemoradiation. Cancer. 2008;113(1):57–64. https://doi.org/10.1002/cncr.23516. Jager T, Neureiter D, Urbas R, et al. Applicability of American Joint Committee on cancer and college of american pathologists regression grading system in rectal cancer. Dis Colon Rectum. 2017;60(8):815–26. https://doi.org/10.1097/DCR.0000000000000806. Trakarnsanga A, Gonen M, Shia J, et al. Comparison of tumor regression grade systems for locally advanced rectal cancer after multimodality treatment. J Natl Cancer Inst. 2014. https://doi.org/10.1093/jnci/dju248. Huh JW, Kim HC, Kim SH, et al. Tumor regression grade as a clinically useful outcome predictor in patients with rectal cancer after preoperative chemoradiotherapy. Surgery. 2019;165(3):579–85. https://doi.org/10.1016/j.surg.2018.08.026. Habr-Gama A, Perez RO, Wynn G, et al. Complete clinical response after neoadjuvant chemoradiation therapy for distal rectal cancer: characterization of clinical and endoscopic findings for standardization. Dis Colon Rectum. 2010;53(12):1692–8. https://doi.org/10.1007/DCR.0b013e3181f42b89. Liu S, Zhong GX, Zhou WX, et al. Can endorectal ultrasound, mri, and mucosa integrity accurately predict the complete response for mid-low rectal cancer after preoperative chemoradiation? A prospective observational study from a single medical center. Dis Colon Rectum. 2018;61(8):903–10. https://doi.org/10.1097/DCR.0000000000001135. Murahashi S, Akiyoshi T, Sano T, et al. Serial circulating tumour DNA analysis for locally advanced rectal cancer treated with preoperative therapy: prediction of pathological response and postoperative recurrence. Br J Cancer. 2020;123(5):803–10. https://doi.org/10.1038/s41416-020-0941-4.