Optimization of combined treatment for locally advanced distal rectal cancer with regard to prognosis factors | Ukrainian Medical Journal

Zvirych V.V.,Michailovich Y.I.

Main
Publications
Optimization of combined treatment for locally advanced distal rectal cancer with regard to prognosis factors

Optimization of combined treatment for locally advanced distal rectal cancer with regard to prognosis factors

April 16, 2020

1003

Keywords :

distal locally-advanced rectal cancer,

molecular and genetic marker,

prognostic factor

Specialities :

Oncology, Hematology

Resume

The current concept of neoadjuvant chemoradiotherapy (NCRT), as a key method in achieving complete or partial tumor’s radiological response to therapy enables to improve the immediate and long-term results of rectal cancer treatment. The purpose of this study was to define prognostic factors for the effectiveness of NCRT in achieving a tumor-radiological response on therapy in patients with local advanced distal rectal cancer (LADRC), as well as factors to prognosion free survival using molecular 8-oxo-2’-deoxyguanosine (8-оксо-dG), immunohistochemical (Ki67) and molecular genetics (GSTP1 and MTHFR genes polymorphism) markers. Materials and methods. GSTP1 and MTHFR gene polymorphisms were determined in real-time on tumor material obtained from 110 patients with LADRC by real-time allele-specific polymerase chain reaction. Level of the 8-оксо-dG in the eluate was performed with spectrophotometric method. Immunohistochemical studies of the Ki-67, MutS 2–6, CD44, and CEA markers were carried out according to standard methods. Results. In patients with LADRC from both study groups, there were significant pathological responses of the tumor to NCRT: in the comparison group it was 47.2%, in the main group — 59.7% suitably to the mrTRG scale and 49.1% and 64.9% with RECIST 1.1 criteria, respectively. It was found that oxaliplatin-containing chemotherapy promotes statistically significant decrease in 8-оксо-dG’s level. The use of single capacetabine in neoadjuvant regimen for patients with LADRC in presence as A313G GSTP1 and C667T MTHFR polymorphisms does not affect increase on relapse-free survival. When combined GSTP1, MTFR and Ki67 factors they are determined predicted probability of recurrence in this patients within 51–99%. Conclusion. The use of capacetabine in NCRT for patients with LADRC is effective only in absence of polymorphisms A313G GSTP1 and C667T MTHFR, in other cases it is desirable to use as NCRT scheme CAPOX. 8-оксо-dG reduction level can serve as independent prognostic factor of NCRT efficacy.

References:

Ali-Osman F., Akande O., Antoun G. et al. (1997) Molecular cloning, characterization, and expression in Escherichia coli of full-length cDNAs of three human glutathione S-transferase Pi gene variants. Evidence for differential catalytic activity of the encoded proteins. J. Biol. Chem., 272(15): 10004–10012.
Amin M.B., Greene F.L., Edge S.B. et al. (2017) The eighth edition AJCC Cancer Staging Manual:continuing to build a bridge from a population-based to a more «personalized» approach to cancer staging. CA Cancer J. Clin., 67: 93–99.
Arnold M., Sierra M.S., Laversanne M. et al. (2017) Global patterns and trends in colorectal cancer incidence and mortality. Gut, 66(4): 683–691.
Aschele C., Cionini L., Lonardi S. et al. (2011) Primary tumor response to preoperative chemoradiation with or without oxaliplatin in locally advanced rectal cancer: pathologic results of the STAR-01 randomized phase III trial. J. Clin. Oncol., 29: 2773–2780.
Bartley A.N., Hamilton S.R., Alsabeh R. et al. (2014) Template for reporting results of biomarker testing of specimens from patients with carcinoma of the colon and rectum. Arch. Pathol. Lab. Med., 138(2): 166–170.
Battaglin F., Naseem M., Lenz H.J. et al. (2018) Microsatellite Instability in Colorectal Cancer: Overview of Its Clinical Significance and Novel Perspectives. Clin. Adv. Hematol. Oncol., 16(11): 735–747.
Berger N.A. (2018) Young Adult Cancer:Influence of the Obesity Pandemic. Obesity, 26(4): 641–502.
Bhangu A., Beynon J., Brown G. et al. (2013) Consensus statement on the multidisciplinary management of patients with recurrent and primary rectal cancer beyond total mesorectal excision planes. Br. J. Surg., 100(8): 1009–1014.
Bourguignon L.Y., Shiina М., Li J.J. (2014) Hyaluronan-CD44 Interaction Promotes Oncogenic Signaling, microRNA Functions, Chemoresistance, and Radiation Resistance in Cancer Stem Cells Leading to Tumor Progression. Adv. Cancer Res., 123: 255–275.
Burlaka A.A., Vovk A.V., Zvirych V.V. et al. (2019) Role of the adipose tissue in the rectal cancer microenvironment. Klin. Onkol., 9(1): 30–33.
Burlaka A.P., Vovk A.V., Burlaka A.А. et al. (2018) Metabolism of adjacent adipose tissue and body mass of the patients with stage III–IV colorectal cancer. Oncology, 20(3): 206–211.
Castiglia P., Sanna V., Azara A. (2019) Methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms in breast cancer: a Sardinian preliminary case-control study. Int. J. Med. Sci., 16: 1089–1095.
Cedermark B., Dahlberg M., Glimelius B. et al. (1997) Improved survival with preoperative radiotherapy in resectable rectal cancer. N. Engl. J. Med., 336: 980–987.
Chang H., Jiang W., Ye W.J. et al. (2018) Is long interval from neoadjuvant chemoradiotherapy to surgery optimal for rectal cancer in the era of intensity-modulated radiotherapy: a prospective observational study. Onco Targets Ther., 11: 6129–6138.
Chen K., Xie G., Zhang Q. et al. (2018) Comparison of short-course with long-course preoperative neoadjuvant therapy for rectal cancer: a meta-analysis. J. Cancer Res. Ther., 14: 224–231.
Chen Y.C., Tzeng C.H., Chen P.M. et al. (2010) Influence of GSTP1 I105V polymorphism on cumulative neuropathy and outcome of FOLFOX-4 treatment in Asian patients with colorectal carcinoma. Cancer Sci., 101: 530–535.
Chéradame S., Etienne M.C., Chazal M. et al. (1997) Relevance of tumoral folylpolyglutamate synthetase and reduced folates for optimal 5-fluorouracil efficacy: experimental data. Eur. J. Cancer, 33: 950–959.
Chiavarina В., Martinez-Outschoorn U.E., Whitaker-Menezes D. et al. (2012) Metabolic reprogramming and two-compartment tumor metabolism: opposing role (s) of HIFla and HIF2a in tumor-associated fibroblasts and human breast cancer cells. Cell Cycle, 11: 3280–3289.
Crott J.W., Mason J.B. (2005) MTHFR Polymorphisms and colorectal neoplasia. In: P.M. Ueland, R. Rozen (Eds.) MTHFR polymorphisms and disease. Texas, Landes Bioscience, p. 178–196.
Dalerba P., Dylla S.J., Park I.K. et al. (2007) Phenotypic characterization of human colorectal cancer stem cells. Proc. Natl. Acad. Sci. USA, 104(24): 10158–10163.
Das P., Shaik A.P., Bammidi V.K. (2013) Meta-analysis study of glutathione-S-transferases (GSTT1, GSTM1) gene polymorphisms and risk of acute myeloid leukemia. Leuk. Lymphoma, 50(8): 1345–1351.
de Campos-Lobato L.F., Geisler D.P., da Luz Moreira A. et al. (2011) Neoadjuvant therapy for rectal cancer: the impact of longer interval between chemoradiation and surgery. J. Gastrointest. Surg., 15(3): 444–450.
Debove С., Maggiori L., Chau A. el al. (2015) Risk factors for circumferential R1 resection after neoadjuvant radiochemotherapy and laparoscopic total mesorectal excision: a study in 233 consecutive patients with mid or low rectal cancer. Int. J. Colorectal. Dis., 30(2): 197–203.
Dienstmann R., Mason M.J., Sinicrope F.A. et al. (2017) Prediction of overall survival in stage II and III colon cancer beyond TNM system: a retrospective, pooled biomarker study. Ann. Oncol., 28(5): 1023–1031.
Du D., Su Z., Wang D. et al. (2018) Optimal interval to surgery after neoadjuvant cemoradiotherapy in rectal cancer: a systematic review and meta-analysis. Clin. Colorectal. Cancer, 17: 13–24.
Du L., Wang H., He L. et al. (2008) CD44 is of functional importance for colorectal cancer stem cells. Clin. Cancer Res., 14: 6751–6760.
Fedorenko Z.P., Mihailovich Y.I., Gulak L.O. et al. (2018) Cancer in Ukraine, 2016–2017. Incidence, mortality, activities of oncological service. Bulletin of National cancer registry of Ukraine. Kyiv, 136 р.
Fedorenko Z.P., Mihailovich Y.I., Gulak L.O. et al. (2019) Cancer in Ukraine, 2017–2018. Incidence, mortality, activities of oncological service. Bulletin of National cancer registry of Ukraine. Kyiv, 101 р.
Fleshman J., Branda M., Sargent D.J. et al. (2015) Effect of Laparoscopic-Assisted Resection vs OpenResection of Stage II or III Rectal Cancer on Pathologic Outcomes:The ACOSOGZ6051 Randomized Clinical Trial. JAMA, 314(13): 1346–1355.
Freisling H., Arnold M., Soerjomataram I. et al. (2017) Comparison of general obesity and measures of body fat distribution in older adults in relation to cancer risk: meta-analysis of individual participant data of seven prospective cohorts in Europe. Br. J. Cancer, 116(11): 1486–1497.
Gérard J.P., Azria D., Gourgou-Bourgade S. et al. (2012) Clinical outcome of the ACCORD 12/0405 PRODIGE 2 randomized trial in rectal cancer. J. Clin. Oncol., 36: 4558–4565.
Gerard J.P., Conroy T., Bonnetain F. et al. (2006) Preoperative radiotherapy with or without concurrent fluorouracil and leucovorin in T3–4 rectal cancers: results of FFCD 9203. J. Clin. Oncol., 24: 4620–4625.
Gerdes J., Lemke H., Baisch H. et al. (1984) Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67. J. Immunol., 133(4): 1710–1715.
Girelli D., Friso S., Trabetti E. et al. (1998) Methylenetetrahydrofolate reductase C677T mutation, plasmahomocysteine, and folate in subjects from northern Italy with or without angiographically documented severe coronary atherosclerotic disease: evidence for an important genetic-environmental interaction. Blood, 91(11): 4158–4163.
Glimelius B., Martling A. (2017) What conclusions can be drawn from the Stockholm III rectal cancer trial in the era of watch and wait? Acta Oncol., 56(9): 1139–1142.
Goyette P., Sumner J.S., Milos R. et al. (1994) Human methylenetetrahydrofolate reductase:isolation of cDNA, mapping and mutation identification. Nat. Genet., 7: 195–200.
Guillou P.J., Quirke P., Thorpe H. et al. (2005) MRC CLASICC trial group. Short-term endpoints of conventional versus laparoscopic-assisted surgery in patients with colorectal cancer (MRC CLASICCtrial): multicentre, randomised controlled trial. Lancet, 365(9472): 1718–1726.
Habr-Gama A., Perez R.O., Proscurshim I. et al. (2008) Interval between surgery and neoadjuvant chemoradiation therapy for distal rectal cancer:does delayed surgery have an impact on outcome? Int. J. Radiat. Oncol. Biol. Phys., 71: 1181–1188.
Hayashi H., Beppu T., Sakamoto Y. et al. (2015) Prognostic value of Ki-67 expression in conversion therapy for colorectal liver-limited metastases. Am. J. Cancer Res., 5(3): 1225–1233.
Heald R.J., Husband E.M., Ryall R.D. (1982) The mesorectum in rectal cancer surgery — the clue to pelvic recurrence? Br. J. Surg., 69(10): 613–616.
Heald R.J., Ryall R.D. (1986) Recurrence and survival after total mesorectal excisionfor rectal cancer. Lancet, 1(8496): 1479–1482.
Hong I., Hong S.W., Chang Y.G. et al. (2015) Expression of the cancer stem cell markers CD44 and CD133 in colorectal cancer: an immunohistochemical staining analysis. Ann. Coloproctol., 31: 84–91.
Huh J.W., Kim H.R., Kim Y.J. (2013) Clinical prediction of pathological complete response after preoperative chemoradiotherapy for rectal cancer. Dis. Colon. Rectum, 56: 698–703.
Ivanecz A., Kavalar R., Palfy M. et al. (2014) Can we improve the clinical risk score? The prognostic value of p53, Ki-67 and thymidylate synthase in patients undergoing radical resection of colorectal liver metastases. HPB (Oxford), 16(3): 235–242.
Jeong S.Y., Park J.W., Nam B.H. et al. (2014) Open versus laparoscopic surgery for mid-rectal or low-rectal cancer after neoadjuvant chemoradiotherapy (COREAN trial): survival outcomes ofan open-label, non-inferiority, randomised controlled trial. Lancet Oncol., 15(7): 767–774.
Kalady M.F., de Campos-Lobato L.F., Stocchi L. et al. (2009) Predictive factors of pathologic complete response after neoadjuvant chemoradiation for rectal cancer. Ann. Surg., 250: 582–589.
Kasai H. (1997) Analysis of a form of oxidative DNA damage, 8-hydroxy-2’-deoxyguanosine, as a marker of cellular oxidative stress during carcinogenesis. Mutation Research, 387: 147–163.
Kim C.W., Yu C.S., Yang S.S. et al. (2011) Clinical significance of pre- to post-chemoradiotherapy s-CEA reduction ratio in rectal cancer patients treated with preoperative chemoradiotherapy and curative resection. Ann. Surg. Oncol., 18: 3271–3277.
Libutti S.K., Saltz L.B., Tepper J.E. (2011) Cancer of the Colon. In: V.T. DeVita, T.S. Lawrence, S.A. Rosenberg et al. Cancer: Principles & Practice of Oncology. Philadelphia, Lippincott Williams & Wilkins, p. 1084–1153.
Lin M.X., Wen Z.F., Feng Z.Y., He D. (2008) Expression and significance of Bmi-1 and Ki67 in colorectal carcinoma tissues. Ai. Zheng., 27(12): 1321–1132.
Liu Y., Burness M.L., Martin-Trevino R. et al. (2017) RAD51 mediates resistance of cancer stem cells to PARP inhibition in triple-negative breast cancer. Clin. Cancer Res., 23(2): 514–522.
Lugli A., Iezzi G., Hostettler I. et al. (2010) Prognostic impact of the expression of putative cancer stem cell markers CD133, CD166, CD44s, EpCAM, and ALDH1 in colorectal cancer. Br. J. Cancer, 103(3): 382–390.
Luo Y., Ren F., Liu Y. et al. (2015) Clinicopathological and prognostic significance of high Ki-67 labeling index in hepatocellular carcinoma patients:a meta-analysis. Int. J. Clin. Exp. Med., 8(7): 10235–10247.
Luo Z.W., Zhu M.G., Zhang Z.Q. et al. (2019) Increased expression of Ki-67 is a poor prognostic marker for colorectal cancer patients: a meta analysis. BMC Cancer, 19(1): 123.
Luzietti E., Pellino G., Nikolaou S. et al. (2018) Comparison of guidelines for the management of rectal cancer. BJS Open, 2(6): 433–451.
Manzi L., Costantini L., Molinari R. et al. (2015) Effect of dietary omega-3 polyunsaturated fatty acid DHA on glycolytic enzymes and Warburg phe-notypes in cancer. Biomed. Res. Int., 2015: 1–7.
Marseglia L., Manti S., D’Angelo G. et al. (2015) Oxidative stress in obesity: a critical component in human diseases. Int. J. Mol. Sci., 16(1): 378–400.
Melling N., Kowitz C.M., Simon R. et al. (2016) High Ki67 expression is an independent good prognostic marker in colorectal cancer. J. Clin. Pathol., 69(3): 209–214.
Miles W.E. (1908) A method of performing abdomino-perineal excision for carcinoma of the rectum and of the terminal portion of the pelvic colon. Lancet, II: 1812–1813.
Miskovic D., Foster J., Agha A. et al. (2015) Standardization of laparoscopic total mesorectal excision for rectal cancer:astructured international expert consensus. Ann. Surg., 261(4): 716–722.
Mohile S., Dale W., Somerfield M. et al. (2018) Practical Assessment and Management of Vulnerabilities in Older Patients Receiving Chemotherapy: ASCO Guideline for Geriatric Oncology. J. Oncol. Pract., 14(7): 442–446.
Moore H.G., Gittleman A.E., Minsky B.D. et al. (2004) Rate of pathologic complete response with increased interval between preoperative combined modality therapy and rectal cancer resection. Dis. Colon. Rectum., 47(3): 279–286.
National Comprehensive Cancer Network (2017) NCCN Guidelines for Rectal Cancer Version 3 (https://www.nccn.org/about/news/ebulletin/ebulletindetail.aspx?ebulletinid=1319).
Negi L.M., Talegaonkar S., Jaggi M. et al. (2012) Role of CD44 in tumour progression and strategies for targeting. J. Drug Target., 20: 561–573.
Ngan S.Y., Burmeister B., Fisher R.J. et al. (2012) Randomized trial of short-course radiotherapy versus long-course chemoradiation comparing rates of local recurrence in patients with T3 rectal cancer: Trans-Tasman Radiation Oncology Group trial. J. Clin. Oncol., 30: 3827–3833.
O’Rourke R.W. (2014) Obesity and cancer: at the crossroads of cel-lular metabolism and proliferation. Surg. Obes. Relat. Dis., 10(6): 1208–1219.
Ogston K.N., Miller I.D., Payne S. et al. (2003) A new histological grading system to assess response of breast cancers to primary chemotherapy: prognostic significance and survival. Breast, 12(5): 320–327.
Pap Z., Ilyes I.A., Mocan S.L. et al. (2015) Changes in immunoexpression of p53, Ki-67, Ets-1, APAF-1 and PTEN in serrated and conventional colon adenomas. Rom. J. Morphol. Embryol., 56(4): 1389–1396.
Pardal R., Clarke M.F., Morrison S.J. (2003) Morrison: applying the principles of stem-cell biology to cancer. Nat. Rev. Cancer, 3(12): 895–902.
Park J.W., Lim S.B., Kim D.Y. et al. (2009) Carcinoembryonic antigen as a predictor of pathological response and prognostic factor in locally advanced rectal cancer patients treated with preoperative chemoradiotherapy and surgery. Int. J. Radiat. Oncol. Biol. Phys., 74: 810–817.
Pereira A.C., Schettert I.T., Morandini Filho A.A. et al. (2004) Methylenetetrahydrofolate reductase (MTHFR) c677t gene variant modulates the homocysteine folate correlation in a mild folatedeficient population. Clin. Chim. Acta, 340: 99–105.
Perez R.O., São Julião G.P., Habr-Gama A. et al. (2009) The role of carcinoembryonic antigen in predicting response and survival to neoadjuvant chemoradiotherapy for distal rectal cancer. Dis. Colon. Rectum., 52: 1137–1143.
Petrelli F., Sgroi G., Sarti E. et al. (2016) Increasing the interval between neoadjuvant chemoradiotherapy and surgery in rectal cancer: a meta-analysis of published studies. Ann. Surg., 263: 458–464.
Pezzilli R., Partelli S., Cannizzaro R. et al. (2016) Ki-67 prognostic and therapeutic decision driven marker for pancreatic neuroendocrine neoplasms (PNENs): A systematic review. Adv. Med. Sci., 61(1): 147–153.
Polat N.D., Degirmencioglu S., Yaren A. et al. (2018) GSTP1, TSER, MTHFR C677T and MTHFR A1298C gene single nucleotide polymorphisms associated with toxicity and survival in patients with colorectal cancer treated with 5‑fluorouracil-based chemotherapy. Cancer Rep. Rev., 2(2): 1–7.
Ponta H., Sherman L., Herrlich P.A. (2003) CD44: from adhesion molecules to signalling regulators. Nat. Rev. Mol. Cell Biol., 4: 33–45.
Probst C.P., Becerra A.Z., Aquina C.T. et al. (2016) Watch and Wait? Elevated pretreatment CEA is associated with decreased pathological complete response in rectal cancer. J. Gastrointest. Surg., 20: 43–52.
Quirke P., Durdey P., Dixon M.F., Williams N.S. (1986) Local recurrence of rectal adenocarcinoma due to inadequate surgical resection. Histopathological study of lateral tumour spread and surgical excision. Lancet, 2(8514): 996–999.
Richards-Taylor S., Ewings S.M., Jaynes E. et al. (2016) Review the assessment of Ki-67 as a prognostic marker in neuroendocrine tumours:a systematic review and meta-analysis. J. Clin. Pathol., 69(7): 612–618.
Rödel C., Graeven U., Fietkau R. et al. (2015) Oxaliplatin added to fluorouracilbased preoperative chemoradiotherapy and postoperative chemotherapy of locally advanced rectal cancer (the German CAO/ARO/AIO-04 study): final results of the multicentre, open-label, randomised, phase 3 trial. Lancet Oncol., 16: 979–989.
Said A.H., Raufman J.P., Xie G. (2014) The role of matrix metalloproteinases in colorectal cancer. Cancers Basel., 6(1): 366–375.
Salminen E., Palmu S., Vahlberg T. et al. (2005) Increased proliferation activity measured by immunoreactive Ki67 is associated with survival improvement in rectal/recto sigmoid cancer. World J. Gastroenterol., 11(21): 3245–3245.
Sauer R., Becker H., Hohenberger W. et al. (2004) Preoperative versus postoperative chemoradiotherapy for locally advanced rectal cancer: results of the German CAO/ARO/AIO-94 randomized phase III trial after a median follow-up of 11 years. N. Engl. J. Med., 351(17): 1731–1740.
Sauer R., Liersch T., Merkel S. et al. (2012) Preoperative versus postoperative chemoradiotherapy for locally advanced rectal cancer:results of the German CAO/ARO/IO–94 randomized phase III trial after a median follow-up of 11 years. J. Clin. Oncol., 30: 1926–1933.
Schmoll H., Haustermans K., Price T.J. et al. (2014) Preoperative chemoradiotherapy and postoperative chemotherapy with capecitabine and oxaliplatin versus capecitabine alone in locally advanced rectal cancer: Disease-free survival results at interim analysis. J. Clin. Oncol., 32(15): 3501–3501.
Schmoll H., Haustermans K., Price T.J. et al. (2018) Preoperative chemoradiotherapy and postoperative chemotherapy with capecitabine +/– oxaliplatin in locally advanced rectal cancer: Final results of PETACC-6. J. Clin. Oncol., 36(15): 3500.
Sen A., Mitra S., Das R.N. et al. (2015) Expression of CDX-2 and Ki-67 in different grades of colorectal adenocarcinomas. Indian J. Pathol. Microbiol., 58(2): 158–162.
Sharma R., Hoskins J.M., Rivory L.P. et al. (2008) Thymidylate Synthase and Methylenetetrahydrofolate Reductase Gene Polymorphisms and Toxicity to Capecitabine in Advanced Colorectal Cancer Patients. Clin. Cancer Res., 14(3): 817–825.
Shimada T., Murayama N., Yamazaki H. et al. (2013) Metabolic Activation of Polycyclic Aromatic Hydrocarbons and Aryl and Heterocyclic Amines by Human Cytochromes P450 2A13 and 2A6. Chem. Res. Toxicol., 26(4): 529–537.
Stevenson A.R., Solomon M.J., Lumley J.W. et al. (2015) ALaCaRT Investigators. Effect of Laparoscopic-Assisted Resection vs Open Resection on Pathological Outcomes in Rectal Cancer: The ALaCaRT Randomized Clinical Trial. JAMA, 314(13): 1356–1363.
Taylor F.G., Quirke P., Heald R.J. et al. (2014) Magnetic Resonance Imaging in Rectal Cancer European Equivalence Study Study Group. Preoperative magnetic resonanceimaging assessment of circumferential resection margin predicts disease-freesurvival and local recurrence: 5-year follow-up results of the MERCURY study. J. Clin. Oncol., 32(1): 34–43.
Tsai M.J., Chang W.A., Huang M.S., Kuo P.L. (2014) Tumor microenvironment: A new treatment target for cancer. ISRN Biochemistry, 2014: 351959.
Tulchinsky H., Shmueli E., Figer A. et al. (2008) An interval >7 weeks between neoadjuvant therapy and surgery improves pathologic complete response and disease-free survival in patients with locally advanced rectal cancer. Ann. Surg. Oncol., 15: 2661–2667.
Turesky R.J. (2004) The role of genetic polymorphisms in metabolism of carcinogenic heterocyclic aromatic amines. Curr. Drug Metab., 5: 169–180.
van der Pas M.H., Haglind E., Cuesta M.A. et al. (2013) Colorectal cancer Laparoscopic or Open Resection II (COLOR II) Study Group. Laparoscopic versus open surgery for rectal cancer (COLOR II): short-termoutcomes of a randomised, phase 3 trial. Lancet Oncol., 14(3): 210–218.
Verseveld M., de Graaf E.J., Verhoef C. et al. (2015) CARTS Study Group. Chemoradiation therapy for rectal cancer in the distal rectum followed by organ-sparing transanal endoscopic microsurgery (CARTS study). Br. J. Surg., 102(7): 853–860.
Wang H., Naghavi M., Allen C. et al. (2015) Global, regional and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980–2015: a systematic analysis for the Global Burden of Disease Study. Lancet, 388(10053): 1459–1544.
Wang Z., Tang Y., Xie L. et al. (2019) The Prognostic and Clinical Value of CD44 in Colorectal Cancer: A Meta-Analysis. Front. Oncol., 9: 309.
Weisberg I., Tran P., Christensen B. et al. (1998) A second genetic polymorphism in methylenetetrahydrofolate reductase (MTHFR) associated with decreased enzyme activity. Mol. Genet. Metab., 64: 169–172.
Wu Q., Yang Y., Wu S. et al. (2015) Evaluation of the correlation of KAI1/CD82, CD44, MMP7 and β-catenin in the prediction of prognosis and metastasis in colorectal carcinoma. Diagn. Pathol., 10(1): 176–185.
Yang J., Ling X., Tang W. et al. (2019) Analyses of predictive factors for pathological complete remission in neoadjuvant therapy for locally advanced rectal cancer. J. BUON, 24(1): 77–83.
Yeo S.G. (2016) Association of pretreatment serum carcinoembryonic antigen levels with chemoradiation-induced downstaging and downsizing of rectal cancer. Mol. Clin. Oncol., 4: 631–635.
Zhao M., Li X., Xing C. et al. (2013) Association of methylenetetrahydrofolate reductase C677T and A1298C polymorphisms with colorectal cancer risk: a meta-analysis. Biomed. Rep., 1: 781–791.