The prognostic significance of tumor epidermal growth factor receptor (EGFR) expression change after neoadjuvant chemoradiation in patients with rectal adenocarcinoma

. 2015 ; 19 (1) : 48-53. [epub] 20150326

Status PubMed-not-MEDLINE Jazyk angličtina Země Polsko Médium print-electronic

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/pmid26199571

AIM OF THE STUDY: The aim of this retrospective study was to determine the prognostic impact of epidermal growth factor receptor (EGFR) expression changes during neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer. MATERIAL AND METHODS: Fifty patients with locally advanced rectal cancer were evaluated. All the patients were administered the total dose of 44 Gy. Capecitabine has been concomitantly administered in the dose 825 mg/m(2) in two daily oral administrations. Surgery was indicated 4-8 weeks from the chemoradiotherapy completion. Epidermal growth factor receptor expression in the pretreatment biopsies and in the resected specimens was assessed with immunohistochemistry. RESULTS: All of 50 patients received radiotherapy without interruption up to the total planned dose. In 30 patients sphincter-saving surgery was performed, 20 patients underwent amputation of the rectum. Downstaging was described in 30 patients. Four patients have had complete pathologic remission. Twenty-six patients have had partial remission, the disease was stable in 15 patients. Progression was reported in 5 patients. The median disease-free survival was 64.9 months, median overall survival was 76.4 months. Increased EGFR expression was found in 12 patients (26.1%). A statistically significantly shorter overall survival (p < 0.0001) and disease-free survival (p < 0.0001) was found in patients with increased expression of EGFR compared with patients where no increase in the expression of EGFR during neoadjuvant chemoradiotherapy was observed. CONCLUSIONS: The overexpression of EGFR during neoadjuvant chemoradiotherapy for locally advanced rectal adenokarcinoma associated with significant shorter overall survival and disease free survival.

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Sauer R, Liersch T, Merkel S, et al. Preoperative versus postoperative chemoradiotherapy for rectal cancer: results of the German CAO/ARO/AIO-94 randomised phase III trial after a median follow-up of 11 years. J Clin Oncol. 2012;30:1923–33. PubMed

Bosset JF, Calais G, Mineur L, et al. Enhanced tumorocidal effect of chemotherapy with preoperative radiotherapy for rectal cancer: preliminary results EORTC 22921. J Clin Oncol. 2005;23:5620–7. PubMed

Gérard JP, Conroy T, Bonnetain F, et al. Preoperative radiotherapy with or without concurrent fluorouracil and leucovorine in T3-4 rectal cancers: results of FFCD 9203. J Clin Oncol. 2006;24:4620–5. PubMed

Hofheinz RD, Wenz F, Post S, et al. Chemoradiotherapy with capecitabine versus fluorouracil for locally advanced rectal cancer: a randomised, multicentre, non-inferiority, phase 3 trial. Lancet Oncol. 2012;13:579–88. PubMed

De Caluwé L, Van Nieuwenhove Y, Ceelen WP. Preoperative chemoradiation versus radiation alone for stage II and III resectable rectal cancer. Cochrane Database Syst Rev. 2013;2:CD006041. PubMed PMC

Steele RJ, Kelly P, Ellul B, Eremin O. Epidermal growth factor receptor expression in colorectal cancer. Br J Surg. 1990;77:1352–4. PubMed

Mayer A, Takimoto M, Fritz E, Schellander G, Kofler K, Ludwig H. The prognostic significance of proliferating cell nuclear antigen, epidermal growth factor receptor, and MDR gene expression in colorectal cancer. Cancer. 1993;71:2454–60. PubMed

Khorana AA, Ryan CK, Cox C, Eberly S, Sahasrabudhe DM. Vascular endothelial growth factor, CD68, and epidermal growth factor receptor expression and survival in patients with stage II and stage III colon carcinoma: a role for the host response in prognosis. Cancer. 2003;97:960–8. PubMed

Withers HR, Taylor JM, Maciejewski B. The hazard of accelerated tumor clonogen repopulation during radiotherapy. Acta Oncol. 1988;27:131–46. PubMed

Baumann M, Petersen C, Eichler W. Mechanism of repopulation in experimental squamos cell carcinoma. In: Kogelnik HD, Lukas P, Sedlmayer F, et al., editors. Progress in radiation-oncology. Bologna: Monduzzi; 2002. pp. 417–22.

Begg AC. Prediction of repopulation rates and radiosensitivity in human tumours. Int J Radiat Biol. 1994;65:103–8. PubMed

Fowler JF. Rapid repopulation in radiotherapy: a debate on mechanism. The phantom of tumor treatment-continually rapid proliferation inmasked. Radiother Oncol. 1991;22:156–8. PubMed

Schmidt-Ullrich RK, Contessa JN, Dent P, Mikkelsen RB, Valerie K, Reardon DB, Bowers G, Lin PS. Molecular mechanism of radiation-induced accelerated repopulation. Radiat Oncol Investig. 1999;7:321–30. PubMed

Cunningham D, Humblet Y, Siena S, et al. Cetuximab monotherapy and cetuximab plus irinotekan in irinotekan-refractory metastatic colorectal cancer. N Engl J Med. 2004;351:337–45. PubMed

Van Cutsem E, Köhne CH, Láng I. Cetuximab plus irinotecan, fluorouracil, and leucovorine as fist-line treatment for metastatic colorectal cancer: update analysis of overall survival according to tumor KRAS and BRAF station status. J Clin Oncol. 2011;29:2011–9. http://www.ncbi.nlm.nih.gov/pubmed/?term=Folprecht%20G%5BAuthor%5D&cauthor=true&cauthor_uid=21502544etal. PubMed

Van Cutsem E, Peeters M, Siena S, et al. Open label phase III trial of panitumumab plus best supportive care compared with best supportive care alone in patiens with chemotherapy-refractory metastatic colorectal cancerm. J Clin Oncol. 2007;25:1658–64. PubMed

Oliner KS, Douillard JY, Siena S, et al. Analysis of KRAS/NRAS and BRAF station in the phase III PRIME study of panitumumab (pmab) plus FOLFOX versus FOLFOX as first-line treatment (tx) for metastatic colorectal cancer (mCRC) J Clin Oncol. 2013;31(Suppl) Abstract 3511.

Krawczyk P, Kowalski DM. Genetic and immune factors underlying the efficacy of cetuximab and panitumumab in the treatment of patients with metastatic colorectal cancer. Contemp Oncol. 2013;17:413–22. PubMed PMC

Rödel C, Arnold D, Hipp M, et al. Phase I-II trial of cetuximab, capecitabine, oxaliplatin, and radiotherapy as preoperative treatment in rectal cancer. Int J Radiat Oncol Biol Phys. 2008;70:1081–6. PubMed

Bertolini F, Chiara S, Bengala C, et al. Neoadjuvant treatment with single-agent cetuximab followed by 5-FU, cetuximab, and pelvic radiotherapy: a phase II study in locally advanced rectal cancer. Int J Radiat Oncol Biol Phys. 2009;73:466–72. PubMed

Machiels JP, Sempoux C, Scalliet P, et al. Phase I/II study of preoperative cetuximab, capecitabine, and external beam radiotherapy in patients with rectal cancer. Ann Oncol. 2007;18:738–44. PubMed

Hartley A, Ho KF, McConkey C, Geh JI. Pathological komplete response following preoperative chemoradiotheraoy in rectal cancer: analysis of phase II/III trials. Br J Radiol. 2005;78:934–8. PubMed

Pinto C, Di Fabio F, Maiello E, et al. Phase II study of panitumumab, oxaliplatin, 5-fluorouracil, and concurrent radiotherapy as preoperative treatment in high-risk locally advanced rectal cancer patients (StarPan/STAR-02 Study) Ann Oncol. 2011;22:2424–30. PubMed

Šlampa P, Lovas P, Lovasová Z, et al. Karcinomy konečníku. In: Šlampa P, et al., editors. Radiační onkologie v praxi. Brno: Masarykův onkologická ústav; 2011. pp. 70–8.

Dvorak J, Sitorova V, Ryska A, et al. The prognostic significance of changes of tumor epidermal growth factor receptor expression after neoadjuvant chemoradiation in patiens with rectal adenocarcinoma. Strahlenter Onkol. 2012;10:145–7. PubMed

Azria D, Bibeau F, Barbier N, et al. Prognostic impact of epidermal growth factor receptor (EGFR) expression on loco-regional recurrence after preoperative radiotherapy in rectal cancer. BMC Cancer. 2005;5:62. PubMed PMC

Li S, Kim JS, Kim JM, Cho MJ, Yoon WH, Song KS, Yeo SG, Kim JS. Epidermal growth factor receptor as a prognostic factor in locally advanced rectal-cancer patients treated with preoperative chemoradiation. Int J Radiat Oncol Biol Phys. 2006;65:705–12. PubMed

Bengala C, Bettelli S, Bertolini F, et al. Prognostic role of EGFR gene copy number and KRAS station in patiens with locally advanced rectal cancer treated with preoperative chemoradiotherapy. Br J Cancer. 2010;103:1019–24. PubMed PMC

Withers HR. The 4 R's of radiotherapy. In: Lett JT, Alder H, editors. Advances in Radiation Biology. New York: Academic Press; 1975. pp. 241–71.

Lin SY, Makino K, Xia W, Matin A, Wen Y, Kwong KY, Bourguignon L, Hung MC. Nuclear localization of EGF receptor and its potential new role as a transcription factor. Nat Cell Biol. 2001;3:802–8. PubMed

Oksvold M, Huitfeldt H, Stang E, Madshus I. Localizing the EGF receptor. Nat Cell Biol. 2002;4:E22–3. PubMed

Waugh MG, Hsuan JJ. EGF receptors as transcription factors: ridiculous or sublime? Nat Cell Biol. 2001;3:E209–E11. PubMed

Bandyopadhyay D, Mandal M, Adam L, Mendelsohn J, Kumar R. Physical interaction between epidermal growth factor receptor and DNA-dependent protein kinase in mammalian cells. J Biol Chem. 1998;273:1568–73. PubMed

Meyn RE, Munshi A, Haymach JV, Milas L, Ang KK. Receptor signalling as a regulatory mechanism of DNA repair. Radiother Oncol. 2009;92:316–22. PubMed PMC

Krawczyk P, Mlak R, Powrózek T, Nicoś M, Kowalski DM, Wojas-Krawczyk K, Milanowski J. Mechanisms of resistence to reversible inhibitors of EGFR tyrosine kinase in non-small cell lung cancer. Contemp Oncol (Pozn) 2012;16:401–6. PubMed PMC

Chinnaiyan P, Huang S, Vallabhaneni G, Armstrong E, Varambally S, Tomlins SA, Chinnaiyan AM, Harari PM. Mechanism of enhanced radiation response following epidermal growth factor receptor signaling inhibition by erlotinib (Tarceva) Cancer Res. 2005;65:3328–35. PubMed

Nyati MK, Morgan MA, Feng FY, Lawrence TS. Integration of EGFR inhibitors with radiochemotherapy. Nat Rev Cancer. 2006;6:876–85. PubMed

Rau B, Sturm I, Lage H, et al. Dynamic expression profile of p21WAF1/CIP1 and Ki-67 predicts survival in rectal carcinoma treated with preoperative radiochemotherapy. J Clin Oncol. 2003;21:3391–401. PubMed

Kopp R, Rothbauer E, Ruge M, et al. Clinical implications of the EGF receptor ligand system for tumour progression and survival in gastrointestinal carcinomas: evidence for new therapeutic options. Recent Results Cancer Res. 2003;162:115–32. PubMed

Giralt J, de las Heras M, Cerezo L, et al. The expression of epidermal growth factor receptor results in a worse prognosis for patients with rectal cancer treated with preoperative radiotherapy. Radiother Oncol. 2005;74:101–8. PubMed

Mishani E, Abourbeh G. Cancer molecular imaging: radionuclide-based biomarkers of the epidermal growth factor receptor (EGFR) Curr Top Med Chem. 2007;7:1755–72. PubMed

This study was supported by the Scientific Board of Regional Hospital Liberecand, Research Project UK – LF HK: PRVOUK P37/06.

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