The potential predictive value of tumor budding for neoadjuvant chemoradiotherapy response in locally advanced rectal cancer

go back to reference Kapiteijn E, Marijnen CA, Nagtegaal ID, Putter H, Steup WH, Wiggers T, Rutten HJ, Pahlman L, Glimelius B, van Krieken JH, Leer JW, van de Velde CJ, Dutch Colorectal Cancer Group (2001) Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Engl J Med 345:638–646. https://doi.org/10.1056/NEJMoa010580 CrossRefPubMed Kapiteijn E, Marijnen CA, Nagtegaal ID, Putter H, Steup WH, Wiggers T, Rutten HJ, Pahlman L, Glimelius B, van Krieken JH, Leer JW, van de Velde CJ, Dutch Colorectal Cancer Group (2001) Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Engl J Med 345:638–646. https://​doi.​org/​10.​1056/​NEJMoa010580 CrossRefPubMed

go back to reference Sauer R, Becker H, Hohenberger W, Rödel C, Wittekind C, Fietkau R, Martus P, Tschmelitsch J, Hager E, Hess CF, Karstens JH, Liersch T, Schmidberger H, Raab R, German Rectal Cancer Study Group (2004) Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med 351:1731–1740. https://doi.org/10.1056/NEJMoa040694 CrossRefPubMed Sauer R, Becker H, Hohenberger W, Rödel C, Wittekind C, Fietkau R, Martus P, Tschmelitsch J, Hager E, Hess CF, Karstens JH, Liersch T, Schmidberger H, Raab R, German Rectal Cancer Study Group (2004) Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med 351:1731–1740. https://​doi.​org/​10.​1056/​NEJMoa040694 CrossRefPubMed

go back to reference Ma B, Gao P, Wang H, Xu Q, Song Y, Huang X, Sun J, Zhao J, Luo J, Sun Y, Wang Z (2017) What has preoperative radio(chemo)therapy brought to localized rectal cancer patients in terms of perioperative and long-term outcomes over the past decades? A systematic review and meta-analysis based on 41,121 patients. Int J Cancer 141:1052–1065. https://doi.org/10.1002/ijc.30805 CrossRefPubMed Ma B, Gao P, Wang H, Xu Q, Song Y, Huang X, Sun J, Zhao J, Luo J, Sun Y, Wang Z (2017) What has preoperative radio(chemo)therapy brought to localized rectal cancer patients in terms of perioperative and long-term outcomes over the past decades? A systematic review and meta-analysis based on 41,121 patients. Int J Cancer 141:1052–1065. https://​doi.​org/​10.​1002/​ijc.​30805 CrossRefPubMed

go back to reference Bosset JF, Collette L, Calais G, Mineur L, Maingon P, Radosevic-Jelic L, Daban A, Bardet E, Beny A, Ollier JC, EORTC Radiotherapy Group Trial 22921 (2006) Chemotherapy with preoperative radiotherapy in rectal cancer. N Engl J Med 355:1114–1123. https://doi.org/10.1056/NEJMoa060829 CrossRefPubMed Bosset JF, Collette L, Calais G, Mineur L, Maingon P, Radosevic-Jelic L, Daban A, Bardet E, Beny A, Ollier JC, EORTC Radiotherapy Group Trial 22921 (2006) Chemotherapy with preoperative radiotherapy in rectal cancer. N Engl J Med 355:1114–1123. https://​doi.​org/​10.​1056/​NEJMoa060829 CrossRefPubMed

go back to reference Sauer R, Liersch T, Merkel S, Fietkau R, Hohenberger W, Hess C, Becker H, Raab HR, Villanueva MT, Witzigmann H, Wittekind C, Beissbarth T, Rödel C (2012) 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. J Clin Oncol 30:1926–1933. https://doi.org/10.1200/JCO.2011.40.1836 CrossRefPubMed Sauer R, Liersch T, Merkel S, Fietkau R, Hohenberger W, Hess C, Becker H, Raab HR, Villanueva MT, Witzigmann H, Wittekind C, Beissbarth T, Rödel C (2012) 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. J Clin Oncol 30:1926–1933. https://​doi.​org/​10.​1200/​JCO.​2011.​40.​1836 CrossRefPubMed

go back to reference Fokas E, Liersch T, Fietkau R, Hohenberger W, Beissbarth T, Hess C, Becker H, Ghadimi M, Mrak K, Merkel S, Raab HR, Sauer R, Wittekind C, Rödel C (2014) Tumor regression grading after preoperative chemoradiotherapy for locally advanced rectal carcinoma revisited: updated results of the CAO/ARO/AIO-94 trial. J Clin Oncol 32:1554–1562. https://doi.org/10.1200/JCO.2013.54.3769 CrossRefPubMed Fokas E, Liersch T, Fietkau R, Hohenberger W, Beissbarth T, Hess C, Becker H, Ghadimi M, Mrak K, Merkel S, Raab HR, Sauer R, Wittekind C, Rödel C (2014) Tumor regression grading after preoperative chemoradiotherapy for locally advanced rectal carcinoma revisited: updated results of the CAO/ARO/AIO-94 trial. J Clin Oncol 32:1554–1562. https://​doi.​org/​10.​1200/​JCO.​2013.​54.​3769 CrossRefPubMed

go back to reference Folkesson J, Birgisson H, Pahlman L, Cedermark B, Glimelius B, Gunnarsson U (2005) Swedish Rectal Cancer Trial: long lasting benefits from radiotherapy on survival and local recurrence rate. J Clin Oncol 23:5644–5650. https://doi.org/10.1200/JCO.2005.08.144 CrossRefPubMed Folkesson J, Birgisson H, Pahlman L, Cedermark B, Glimelius B, Gunnarsson U (2005) Swedish Rectal Cancer Trial: long lasting benefits from radiotherapy on survival and local recurrence rate. J Clin Oncol 23:5644–5650. https://​doi.​org/​10.​1200/​JCO.​2005.​08.​144 CrossRefPubMed

go back to reference van Gijn W, Marijnen CA, Nagtegaal ID, Kranenbarg EM, Putter H, Wiggers T, Rutten HJ, Påhlman L, Glimelius B, van de Velde CJ, Dutch Colorectal Cancer Group (2011) Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer: 12-year follow-up of the multicentre, randomised controlled TME trial. Lancet Oncol 12:575–582. https://doi.org/10.1016/S1470-2045(11)70097-3 CrossRefPubMed van Gijn W, Marijnen CA, Nagtegaal ID, Kranenbarg EM, Putter H, Wiggers T, Rutten HJ, Påhlman L, Glimelius B, van de Velde CJ, Dutch Colorectal Cancer Group (2011) Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer: 12-year follow-up of the multicentre, randomised controlled TME trial. Lancet Oncol 12:575–582. https://​doi.​org/​10.​1016/​S1470-2045(11)70097-3 CrossRefPubMed

go back to reference Gérard JP, Conroy T, Bonnetain F, Bouché O, Chapet O, Closon-Dejardin MT, Untereiner M, Leduc B, Francois E, Maurel J, Seitz JF, Buecher B, Mackiewicz R, Ducreux M, Bedenne L (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. https://doi.org/10.1200/JCO.2006.06.7629 CrossRefPubMed Gérard JP, Conroy T, Bonnetain F, Bouché O, Chapet O, Closon-Dejardin MT, Untereiner M, Leduc B, Francois E, Maurel J, Seitz JF, Buecher B, Mackiewicz R, Ducreux M, Bedenne L (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. https://​doi.​org/​10.​1200/​JCO.​2006.​06.​7629 CrossRefPubMed

go back to reference Bosset JF, Calais G, Mineur L, Maingon P, Stojanovic-Rundic S, Bensadoun RJ, Bardet E, Beny A, Ollier JC, Bolla M, Marchal D, Van Laethem JL, Klein V, Giralt J, Clavère P, Glanzmann C, Cellier P, Collette L, EORTC Radiation Oncology Group (2014) Fluorouracil-based adjuvant chemotherapy after preoperative chemoradiotherapy in rectal cancer. Long-term results of the EORTC 22921 randomised study. Lancet Oncol 15:184–190. https://doi.org/10.1016/S1470-2045(13)70599-0 CrossRefPubMed Bosset JF, Calais G, Mineur L, Maingon P, Stojanovic-Rundic S, Bensadoun RJ, Bardet E, Beny A, Ollier JC, Bolla M, Marchal D, Van Laethem JL, Klein V, Giralt J, Clavère P, Glanzmann C, Cellier P, Collette L, EORTC Radiation Oncology Group (2014) Fluorouracil-based adjuvant chemotherapy after preoperative chemoradiotherapy in rectal cancer. Long-term results of the EORTC 22921 randomised study. Lancet Oncol 15:184–190. https://​doi.​org/​10.​1016/​S1470-2045(13)70599-0 CrossRefPubMed

go back to reference Ngan SY, Burmeister B, Fisher RJ, Solomon M, Goldstein D, Joseph D, Ackland SP, Schache D, McClure B, McLachlan SA, McKendrick J, Leong T, Hartopeanu C, Zalcberg J, Mackay J (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 01.04. J Clin Oncol 30:3827–3833. https://doi.org/10.1200/JCO.2012.42.9597 CrossRefPubMed Ngan SY, Burmeister B, Fisher RJ, Solomon M, Goldstein D, Joseph D, Ackland SP, Schache D, McClure B, McLachlan SA, McKendrick J, Leong T, Hartopeanu C, Zalcberg J, Mackay J (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 01.04. J Clin Oncol 30:3827–3833. https://​doi.​org/​10.​1200/​JCO.​2012.​42.​9597 CrossRefPubMed

go back to reference Erlandsson J, Holm T, Pettersson D, Berglund Å, Cedermark B, Radu C, Johansson H, Machado M, Hjern F, Hallböök O, Syk I, Glimelius B, Martling A (2017) Optimal fractionation of preoperative radiotherapy and timing to surgery for rectal cancer (Stockholm III): a multicentre, randomised, non-blinded, phase 3, non-inferiority trial. Lancet Oncol 18:336–346. https://doi.org/10.1016/S1470-2045(17)30086-4 CrossRefPubMed Erlandsson J, Holm T, Pettersson D, Berglund Å, Cedermark B, Radu C, Johansson H, Machado M, Hjern F, Hallböök O, Syk I, Glimelius B, Martling A (2017) Optimal fractionation of preoperative radiotherapy and timing to surgery for rectal cancer (Stockholm III): a multicentre, randomised, non-blinded, phase 3, non-inferiority trial. Lancet Oncol 18:336–346. https://​doi.​org/​10.​1016/​S1470-2045(17)30086-4 CrossRefPubMed

go back to reference Deng Y, Chi P, Lan P, Wang L, Chen W, Cui L, Chen D, Cao J, Wei H, Peng X, Huang Z, Cai G, Zhao R, Huang Z, Xu L, Zhou H, Wei Y, Zhang H, Zheng J, Huang Y, Zhou Z, Cai Y, Kang L, Huang M, Peng J, Ren D, Wang J (2016) Modified FOLFOX6 with or without radiation versus fluorouracil and leucovorin with radiation in neoadjuvant treatment of locally advanced rectal cancer: initial results of the Chinese FOWARC multicenter, open-label, randomized three-arm phase III trial. J Clin Oncol 34:3300–3307. https://doi.org/10.1200/JCO.2016.66.6198 CrossRefPubMed Deng Y, Chi P, Lan P, Wang L, Chen W, Cui L, Chen D, Cao J, Wei H, Peng X, Huang Z, Cai G, Zhao R, Huang Z, Xu L, Zhou H, Wei Y, Zhang H, Zheng J, Huang Y, Zhou Z, Cai Y, Kang L, Huang M, Peng J, Ren D, Wang J (2016) Modified FOLFOX6 with or without radiation versus fluorouracil and leucovorin with radiation in neoadjuvant treatment of locally advanced rectal cancer: initial results of the Chinese FOWARC multicenter, open-label, randomized three-arm phase III trial. J Clin Oncol 34:3300–3307. https://​doi.​org/​10.​1200/​JCO.​2016.​66.​6198 CrossRefPubMed

go back to reference Fokas E, Rödel C (2017) Optimales Fraktionierungsschema und Zeitintervall zwischen Radiotherapie und Operation beim Rektumkarzinom: Die multizentrische, randomisierte Stockholm-III-Studie. Strahlenther Onkol 193:761–762. https://doi.org/10.1007/s00066-017-1181-2 CrossRefPubMed Fokas E, Rödel C (2017) Optimales Fraktionierungsschema und Zeitintervall zwischen Radiotherapie und Operation beim Rektumkarzinom: Die multizentrische, randomisierte Stockholm-III-Studie. Strahlenther Onkol 193:761–762. https://​doi.​org/​10.​1007/​s00066-017-1181-2 CrossRefPubMed

go back to reference Rödel C, Fokas E (2017) Inklusion von Oxaliplatin in die multimodale Behandlung des lokal fortgeschrittenen Rektumkarzinoms. Strahlenther Onkol 193:168–170. https://doi.org/10.1007/s00066-016-1090-9 CrossRefPubMed Rödel C, Fokas E (2017) Inklusion von Oxaliplatin in die multimodale Behandlung des lokal fortgeschrittenen Rektumkarzinoms. Strahlenther Onkol 193:168–170. https://​doi.​org/​10.​1007/​s00066-016-1090-9 CrossRefPubMed

go back to reference Yang YJ, Cao L, Li ZW, Zhao L, Wu HF, Yue D, Yang JL, Zhou ZR, Liu SX (2016) Fluorouracil-based neoadjuvant chemoradiotherapy with or without oxaliplatin for treatment of locally advanced rectal cancer: an updated systematic review and meta-analysis. Oncotarget 7:45513–45524. https://doi.org/10.18632/oncotarget.9995 CrossRefPubMedCentralPubMed Yang YJ, Cao L, Li ZW, Zhao L, Wu HF, Yue D, Yang JL, Zhou ZR, Liu SX (2016) Fluorouracil-based neoadjuvant chemoradiotherapy with or without oxaliplatin for treatment of locally advanced rectal cancer: an updated systematic review and meta-analysis. Oncotarget 7:45513–45524. https://​doi.​org/​10.​18632/​oncotarget.​9995 CrossRefPubMedCentralPubMed

go back to reference Gani C, Zips D (2017) Zeitintervall zwischen neoadjuvanter Radiochemotherapie und Operation beim Rektumkarzinom: Kein Einfluss auf die pathologische Komplettremissionsrate? Strahlenther Onkol 193:91–92. https://doi.org/10.1007/s00066-016-1080-y CrossRefPubMed Gani C, Zips D (2017) Zeitintervall zwischen neoadjuvanter Radiochemotherapie und Operation beim Rektumkarzinom: Kein Einfluss auf die pathologische Komplettremissionsrate? Strahlenther Onkol 193:91–92. https://​doi.​org/​10.​1007/​s00066-016-1080-y CrossRefPubMed

go back to reference Rödel C, Liersch T, Becker H, Fietkau R, Hohenberger W, Hothorn T, Graeven U, Arnold D, Lang-Welzenbach M, Raab HR, Sülberg H, Wittekind C, Potapov S, Staib L, Hess C, Weigang-Köhler K, Grabenbauer GG, Hoffmanns H, Lindemann F, Schlenska-Lange A, Folprecht G, Sauer R, German Rectal Cancer Study Group (2012) Preoperative chemoradiotherapy and postoperative chemotherapy with fluorouracil and oxaliplatin versus fluorouracil alone in locally advanced rectal cancer: initial results of the German CAO/ARO/AIO-04 randomised phase 3 trial. Lancet Oncol 13:679–687. https://doi.org/10.1016/S1470-2045(12)70187-0 CrossRefPubMed Rödel C, Liersch T, Becker H, Fietkau R, Hohenberger W, Hothorn T, Graeven U, Arnold D, Lang-Welzenbach M, Raab HR, Sülberg H, Wittekind C, Potapov S, Staib L, Hess C, Weigang-Köhler K, Grabenbauer GG, Hoffmanns H, Lindemann F, Schlenska-Lange A, Folprecht G, Sauer R, German Rectal Cancer Study Group (2012) Preoperative chemoradiotherapy and postoperative chemotherapy with fluorouracil and oxaliplatin versus fluorouracil alone in locally advanced rectal cancer: initial results of the German CAO/ARO/AIO-04 randomised phase 3 trial. Lancet Oncol 13:679–687. https://​doi.​org/​10.​1016/​S1470-2045(12)70187-0 CrossRefPubMed

go back to reference Rödel C, Graeven U, Fietkau R, Hohenberger W, Hothorn T, Arnold D, Hofheinz RD, Ghadimi M, Wolff HA, Lang-Welzenbach M, Raab HR, Wittekind C, Ströbel P, Staib L, Wilhelm M, Grabenbauer GG, Hoffmanns H, Lindemann F, Schlenska-Lange A, Folprecht G, Sauer R, Liersch T, German Rectal Cancer Study Group (2015) Oxaliplatin added to fluorouracil-based 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. https://doi.org/10.1016/S1470-2045(15)00159-X CrossRefPubMed Rödel C, Graeven U, Fietkau R, Hohenberger W, Hothorn T, Arnold D, Hofheinz RD, Ghadimi M, Wolff HA, Lang-Welzenbach M, Raab HR, Wittekind C, Ströbel P, Staib L, Wilhelm M, Grabenbauer GG, Hoffmanns H, Lindemann F, Schlenska-Lange A, Folprecht G, Sauer R, Liersch T, German Rectal Cancer Study Group (2015) Oxaliplatin added to fluorouracil-based 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. https://​doi.​org/​10.​1016/​S1470-2045(15)00159-X CrossRefPubMed

go back to reference Lefevre JH, Mineur L, Kotti S, Rullier E, Rouanet P, de Chaisemartin C, Meunier B, Mehrdad J, Cotte E, Desrame J, Karoui M, Benoist S, Kirzin S, Berger A, Panis Y, Piessen G, Saudemont A, Prudhomme M, Peschaud F, Dubois A, Loriau J, Tuech JJ, Meurette G, Lupinacci R, Goasgen N, Parc Y, Simon T, Tiret E (2016) Effect of Interval (7 or 11 weeks) Between Neoadjuvant Radiochemotherapy and Surgery on Complete Pathologic Response in Rectal Cancer: A Multicenter, Randomized, Controlled Trial (GRECCAR-6). J Clin Oncol 34:3773–3780. https://doi.org/10.1200/JCO.2016.67.6049 CrossRefPubMed Lefevre JH, Mineur L, Kotti S, Rullier E, Rouanet P, de Chaisemartin C, Meunier B, Mehrdad J, Cotte E, Desrame J, Karoui M, Benoist S, Kirzin S, Berger A, Panis Y, Piessen G, Saudemont A, Prudhomme M, Peschaud F, Dubois A, Loriau J, Tuech JJ, Meurette G, Lupinacci R, Goasgen N, Parc Y, Simon T, Tiret E (2016) Effect of Interval (7 or 11 weeks) Between Neoadjuvant Radiochemotherapy and Surgery on Complete Pathologic Response in Rectal Cancer: A Multicenter, Randomized, Controlled Trial (GRECCAR-6). J Clin Oncol 34:3773–3780. https://​doi.​org/​10.​1200/​JCO.​2016.​67.​6049 CrossRefPubMed

go back to reference Bujko K, Wyrwicz L, Rutkowski A, Malinowska M, Pietrzak L, Kryński J, Michalski W, Olędzki J, Kuśnierz J, Zając L, Bednarczyk M, Szczepkowski M, Tarnowski W, Kosakowska E, Zwoliński J, Winiarek M, Wiśniowska K, Partycki M, Bęczkowska K, Polkowski W, Styliński R, Wierzbicki R, Bury P, Jankiewicz M, Paprota K, Lewicka M, Ciseł B, Skórzewska M, Mielko J, Bębenek M, Maciejczyk A, Kapturkiewicz B, Dybko A, Hajac Ł, Wojnar A, Leśniak T, Zygulska J, Jantner D, Chudyba E, Zegarski W, Las-Jankowska M, Jankowski M, Kołodziejski L, Radkowski A, Żelazowska-Omiotek U, Czeremszyńska B, Kępka L, Kolb-Sielecki J, Toczko Z, Fedorowicz Z, Dziki A, Danek A, Nawrocki G, Sopyło R, Markiewicz W, Kędzierawski P, Wydmański J, Polish Colorectal Study Group (2016) Long-course oxaliplatin-based preoperative chemoradiation versus 5 × 5 Gy and consolidation chemotherapy for cT4 or fixed cT3 rectal cancer: results of a randomized phase III study. Ann Oncol 27:834–842. https://doi.org/10.1093/annonc/mdw062 CrossRefPubMed Bujko K, Wyrwicz L, Rutkowski A, Malinowska M, Pietrzak L, Kryński J, Michalski W, Olędzki J, Kuśnierz J, Zając L, Bednarczyk M, Szczepkowski M, Tarnowski W, Kosakowska E, Zwoliński J, Winiarek M, Wiśniowska K, Partycki M, Bęczkowska K, Polkowski W, Styliński R, Wierzbicki R, Bury P, Jankiewicz M, Paprota K, Lewicka M, Ciseł B, Skórzewska M, Mielko J, Bębenek M, Maciejczyk A, Kapturkiewicz B, Dybko A, Hajac Ł, Wojnar A, Leśniak T, Zygulska J, Jantner D, Chudyba E, Zegarski W, Las-Jankowska M, Jankowski M, Kołodziejski L, Radkowski A, Żelazowska-Omiotek U, Czeremszyńska B, Kępka L, Kolb-Sielecki J, Toczko Z, Fedorowicz Z, Dziki A, Danek A, Nawrocki G, Sopyło R, Markiewicz W, Kędzierawski P, Wydmański J, Polish Colorectal Study Group (2016) Long-course oxaliplatin-based preoperative chemoradiation versus 5 × 5 Gy and consolidation chemotherapy for cT4 or fixed cT3 rectal cancer: results of a randomized phase III study. Ann Oncol 27:834–842. https://​doi.​org/​10.​1093/​annonc/​mdw062 CrossRefPubMed

go back to reference Maas M, Nelemans PJ, Valentini V, Das P, Rödel C, Kuo LJ, Calvo FA, García-Aguilar J, Glynne-Jones R, Haustermans K, Mohiuddin M, Pucciarelli S, Small W Jr, Suárez J, Theodoropoulos G, Biondo S, Beets-Tan RG, Beets GL (2010) Long-term outcome in patients with a pathological complete response after chemoradiation for rectal cancer: a pooled analysis of individual patient data. Lancet Oncol 11:835–844. https://doi.org/10.1016/S1470-2045(10)70172-8 CrossRefPubMed Maas M, Nelemans PJ, Valentini V, Das P, Rödel C, Kuo LJ, Calvo FA, García-Aguilar J, Glynne-Jones R, Haustermans K, Mohiuddin M, Pucciarelli S, Small W Jr, Suárez J, Theodoropoulos G, Biondo S, Beets-Tan RG, Beets GL (2010) Long-term outcome in patients with a pathological complete response after chemoradiation for rectal cancer: a pooled analysis of individual patient data. Lancet Oncol 11:835–844. https://​doi.​org/​10.​1016/​S1470-2045(10)70172-8 CrossRefPubMed

go back to reference Ferrari L, Fichera A (2015) Neoadjuvant chemoradiation therapy and pathological complete response in rectal cancer. Gastroenterol Rep (oxf) 3:277–288. https://doi.org/10.1093/gastro/gov039 CrossRef Ferrari L, Fichera A (2015) Neoadjuvant chemoradiation therapy and pathological complete response in rectal cancer. Gastroenterol Rep (oxf) 3:277–288. https://​doi.​org/​10.​1093/​gastro/​gov039 CrossRef

go back to reference Bhangu A, Wood G, Brown G, Darzi A, Tekkis P, Goldin R (2014) The role of epithelial mesenchymal transition and resistance to neoadjuvant therapy in locally advanced rectal cancer. Colorectal Dis 16:133–143. https://doi.org/10.1111/codi.12482 CrossRef Bhangu A, Wood G, Brown G, Darzi A, Tekkis P, Goldin R (2014) The role of epithelial mesenchymal transition and resistance to neoadjuvant therapy in locally advanced rectal cancer. Colorectal Dis 16:133–143. https://​doi.​org/​10.​1111/​codi.​12482 CrossRef

go back to reference Edge S, Fritz A, Byrd D, Greene F, Compton C, Trotti A (2010) AJCC cancer staging manual, 7th edn. Springer, New York Edge S, Fritz A, Byrd D, Greene F, Compton C, Trotti A (2010) AJCC cancer staging manual, 7th edn. Springer, New York

go back to reference Jäger T, Neureiter D, Urbas R, Klieser E, Hitzl W, Emmanuel K, Dinnewitzer A (2017) Applicability of American Joint Committee on Cancer and College of American pathologists regression grading system in rectal cancer. Dis Colon Rectum 60:815–826. https://doi.org/10.1097/DCR.0000000000000806 CrossRefPubMed Jäger T, Neureiter D, Urbas R, Klieser E, Hitzl W, Emmanuel K, Dinnewitzer A (2017) Applicability of American Joint Committee on Cancer and College of American pathologists regression grading system in rectal cancer. Dis Colon Rectum 60:815–826. https://​doi.​org/​10.​1097/​DCR.​0000000000000806​ CrossRefPubMed

go back to reference Fokas E, Ströbel P, Fietkau R, Ghadimi M, Liersch T, Grabenbauer GG, Hartmann A, Kaufmann M, Sauer R, Graeven U, Hoffmanns H, Raab HR, Hothorn T, Wittekind C, Rödel C, German Rectal Cancer Study Group (2017) Tumor regression grading after preoperative chemoradiotherapy as a prognostic factor and individual-level surrogate for disease-free survival in rectal cancer. J Natl Cancer Inst 109(12).https://doi.org/10.1093/jnci/djx095 CrossRefPubMed Fokas E, Ströbel P, Fietkau R, Ghadimi M, Liersch T, Grabenbauer GG, Hartmann A, Kaufmann M, Sauer R, Graeven U, Hoffmanns H, Raab HR, Hothorn T, Wittekind C, Rödel C, German Rectal Cancer Study Group (2017) Tumor regression grading after preoperative chemoradiotherapy as a prognostic factor and individual-level surrogate for disease-free survival in rectal cancer. J Natl Cancer Inst 109(12).https://​doi.​org/​10.​1093/​jnci/​djx095 CrossRefPubMed

go back to reference De Smedt L, Palmans S, Sagaert X (2016) Tumour budding in colorectal cancer: what do we know and what can we do? Virchows Arch 468:397–408. https://doi.org/10.1007/s00428-015-1886-5 CrossRefPubMed De Smedt L, Palmans S, Sagaert X (2016) Tumour budding in colorectal cancer: what do we know and what can we do? Virchows Arch 468:397–408. https://​doi.​org/​10.​1007/​s00428-015-1886-5 CrossRefPubMed

go back to reference Rogers AC, Gibbons D, Hanly AM, Hyland JM, O’Connell PR, Winter DC, Sheahan K (2014) Prognostic significance of tumor budding in rectal cancer biopsies before neoadjuvant therapy. Mod Pathol 27:156–162. https://doi.org/10.1038/modpathol.2013.124 CrossRefPubMed Rogers AC, Gibbons D, Hanly AM, Hyland JM, O’Connell PR, Winter DC, Sheahan K (2014) Prognostic significance of tumor budding in rectal cancer biopsies before neoadjuvant therapy. Mod Pathol 27:156–162. https://​doi.​org/​10.​1038/​modpathol.​2013.​124 CrossRefPubMed

go back to reference Prall F, Ostwald C (2007) Tumour budding in colorectal carcinoma. Histopathology 50:151–162. https://doi.org/10.1111/j.1365-2559.2006.02551.x CrossRefPubMed Prall F, Ostwald C (2007) Tumour budding in colorectal carcinoma. Histopathology 50:151–162. https://​doi.​org/​10.​1111/​j.​1365-2559.​2006.​02551.​x CrossRefPubMed

go back to reference Bhangu A, Wood G, Mirnezami A, Darzi A, Tekkis P, Goldin R (2012) Epithelial mesenchymal transition in colorectal cancer: Seminal role in promoting disease progression and resistance to neoadjuvant therapy. Surg Oncol 21:316–323. https://doi.org/10.1016/j.suronc.2012.08.003 CrossRefPubMed Bhangu A, Wood G, Mirnezami A, Darzi A, Tekkis P, Goldin R (2012) Epithelial mesenchymal transition in colorectal cancer: Seminal role in promoting disease progression and resistance to neoadjuvant therapy. Surg Oncol 21:316–323. https://​doi.​org/​10.​1016/​j.​suronc.​2012.​08.​003 CrossRefPubMed

go back to reference Kalluri R, Weinberg RA (2009) The basics of epithelial-mesenchymal transition. J Clin Invest 119:1420–1428. https://doi.org/10.1172/JCI39104 CrossRefPubMedCentralPubMed Kalluri R, Weinberg RA (2009) The basics of epithelial-mesenchymal transition. J Clin Invest 119:1420–1428. https://​doi.​org/​10.​1172/​JCI39104 CrossRefPubMedCentralPubMed

go back to reference Mitrovic B, Schaeffer DF, Riddell RH, Kirsch R (2012) Tumor budding in colorectal carcinoma: time to take notice. Mod Pathol 25:1315–1325. https://doi.org/10.1038/modpathol.2012.94 CrossRefPubMed Mitrovic B, Schaeffer DF, Riddell RH, Kirsch R (2012) Tumor budding in colorectal carcinoma: time to take notice. Mod Pathol 25:1315–1325. https://​doi.​org/​10.​1038/​modpathol.​2012.​94 CrossRefPubMed

go back to reference Acloque H, Adams MS, Fishwick K, Bronner-Fraser M, Nieto MA (2009) Epithelial-mesenchymal transitions: the importance of changing cell state in development and disease. J Clin Invest 119:1438–1449. https://doi.org/10.1172/JCI38019 CrossRefPubMedCentralPubMed Acloque H, Adams MS, Fishwick K, Bronner-Fraser M, Nieto MA (2009) Epithelial-mesenchymal transitions: the importance of changing cell state in development and disease. J Clin Invest 119:1438–1449. https://​doi.​org/​10.​1172/​JCI38019 CrossRefPubMedCentralPubMed

go back to reference Mani SA, Guo W, Liao MJ, Eaton EN, Ayyanan A, Zhou AY, Brooks M, Reinhard F, Zhang CC, Shipitsin M, Campbell LL, Polyak K, Brisken C, Yang J, Weinberg RA (2008) The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell 133:704–715. https://doi.org/10.1016/j.cell.2008.03.027 CrossRefPubMedCentralPubMed Mani SA, Guo W, Liao MJ, Eaton EN, Ayyanan A, Zhou AY, Brooks M, Reinhard F, Zhang CC, Shipitsin M, Campbell LL, Polyak K, Brisken C, Yang J, Weinberg RA (2008) The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell 133:704–715. https://​doi.​org/​10.​1016/​j.​cell.​2008.​03.​027 CrossRefPubMedCentralPubMed

go back to reference Morel AP, Lièvre M, Thomas C, Hinkal G, Ansieau S, Puisieux A (2008) Generation of breast cancer stem cells through epithelial-mesenchymal transition. PLoS ONE 3:e2888. https://doi.org/10.1371/journal.pone.0002888 CrossRefPubMedCentralPubMed Morel AP, Lièvre M, Thomas C, Hinkal G, Ansieau S, Puisieux A (2008) Generation of breast cancer stem cells through epithelial-mesenchymal transition. PLoS ONE 3:e2888. https://​doi.​org/​10.​1371/​journal.​pone.​0002888 CrossRefPubMedCentralPubMed

go back to reference Huebner M, Wolff BG, Smyrk TC, Aakre J, Larson DW (2012) Partial pathologic response and nodal status as most significant prognostic factors for advanced rectal cancer treated with preoperative chemoradiotherapy. World J Surg 36:675–683. https://doi.org/10.1007/s00268-011-1409-8 CrossRefPubMed Huebner M, Wolff BG, Smyrk TC, Aakre J, Larson DW (2012) Partial pathologic response and nodal status as most significant prognostic factors for advanced rectal cancer treated with preoperative chemoradiotherapy. World J Surg 36:675–683. https://​doi.​org/​10.​1007/​s00268-011-1409-8 CrossRefPubMed

go back to reference Sannier A, Lefèvre JH, Panis Y, Cazals-Hatem D, Bedossa P, Guedj N (2014) Pathological prognostic factors in locally advanced rectal carcinoma after neoadjuvant radiochemotherapy: analysis of 113 cases. Histopathology 65:623–630. https://doi.org/10.1111/his.12432 CrossRefPubMed Sannier A, Lefèvre JH, Panis Y, Cazals-Hatem D, Bedossa P, Guedj N (2014) Pathological prognostic factors in locally advanced rectal carcinoma after neoadjuvant radiochemotherapy: analysis of 113 cases. Histopathology 65:623–630. https://​doi.​org/​10.​1111/​his.​12432 CrossRefPubMed

go back to reference Du C, Xue W, Li J, Cai Y, Gu J (2012) Morphology and prognostic value of tumor budding in rectal cancer after neoadjuvant radiotherapy. Hum Pathol 43:1061–1067. https://doi.org/10.1016/j.humpath.2011.07.026 CrossRefPubMed Du C, Xue W, Li J, Cai Y, Gu J (2012) Morphology and prognostic value of tumor budding in rectal cancer after neoadjuvant radiotherapy. Hum Pathol 43:1061–1067. https://​doi.​org/​10.​1016/​j.​humpath.​2011.​07.​026 CrossRefPubMed

go back to reference Jessberger J, Erlenbach-Wünsch K, Posselt R, Haderlein M, Agaimy A, Fietkau R, Hartmann A, Distel L (2017) Combination of growth pattern and tumor regression identifies a high-risk group in neoadjuvant treated rectal cancer patients. J Dig Dis 18:283–291. https://doi.org/10.1111/1751-2980.12471 CrossRefPubMed Jessberger J, Erlenbach-Wünsch K, Posselt R, Haderlein M, Agaimy A, Fietkau R, Hartmann A, Distel L (2017) Combination of growth pattern and tumor regression identifies a high-risk group in neoadjuvant treated rectal cancer patients. J Dig Dis 18:283–291. https://​doi.​org/​10.​1111/​1751-2980.​12471 CrossRefPubMed

go back to reference Ofner D, Devries AF, Schaberl-Moser R, Greil R, Rabl H, Tschmelitsch J, Zitt M, Kapp KS, Fastner G, Keil F, Eisterer W, Jäger R, Offner F, Gnant M, Thaler J, TAKO 05/ABCSG R‑02 Trial Investigators (2011) Preoperative oxaliplatin, capecitabine, and external beam radiotherapy in patients with newly diagnosed, primary operable, cT3NxM0, low rectal cancer: a phase II study. Strahlenther Onkol 187:100–107. https://doi.org/10.1007/s00066-010-2182-6 CrossRefPubMed Ofner D, Devries AF, Schaberl-Moser R, Greil R, Rabl H, Tschmelitsch J, Zitt M, Kapp KS, Fastner G, Keil F, Eisterer W, Jäger R, Offner F, Gnant M, Thaler J, TAKO 05/ABCSG R‑02 Trial Investigators (2011) Preoperative oxaliplatin, capecitabine, and external beam radiotherapy in patients with newly diagnosed, primary operable, cT₃NxM0, low rectal cancer: a phase II study. Strahlenther Onkol 187:100–107. https://​doi.​org/​10.​1007/​s00066-010-2182-6 CrossRefPubMed

go back to reference Kogler P, DeVries AF, Eisterer W, Thaler J, Sölkner L, Öfner D, TAKO 05/ABCSG R‑02 Trial Investigators (2018) Intensified preoperative chemoradiation by adding oxaliplatin in locally advanced, primary operable (cT3NxM0) rectal cancer: Impact on long-term outcome. Results of the phase II TAKO 05/ABCSG R‑02 trial. Strahlenther Onkol 194:41–49. https://doi.org/10.1007/s00066-017-1219-5 CrossRefPubMed Kogler P, DeVries AF, Eisterer W, Thaler J, Sölkner L, Öfner D, TAKO 05/ABCSG R‑02 Trial Investigators (2018) Intensified preoperative chemoradiation by adding oxaliplatin in locally advanced, primary operable (cT₃NxM0) rectal cancer: Impact on long-term outcome. Results of the phase II TAKO 05/ABCSG R‑02 trial. Strahlenther Onkol 194:41–49. https://​doi.​org/​10.​1007/​s00066-017-1219-5 CrossRefPubMed

go back to reference Jäger T, Nawara C, Neureiter D, Holzinger J, Öfner-Velano D, Dinnewitzer A (2015) Impact of anastomotic leakage on long-term survival in mid-to-low rectal cancer. Chirurg 86:1072–1082. https://doi.org/10.1007/s00104-015-0090-0 CrossRefPubMed Jäger T, Nawara C, Neureiter D, Holzinger J, Öfner-Velano D, Dinnewitzer A (2015) Impact of anastomotic leakage on long-term survival in mid-to-low rectal cancer. Chirurg 86:1072–1082. https://​doi.​org/​10.​1007/​s00104-015-0090-0 CrossRefPubMed

go back to reference Austrian Society of Pathology Qualitätsstandards in der Pathologie. http://www.pathology.at/images/stories/PDF/Qualitaetsstandards/QS_Kolon_Rektum_V1.0.pdf. Accessed 11 Mar 2017 Austrian Society of Pathology Qualitätsstandards in der Pathologie. http://​www.​pathology.​at/​images/​stories/​PDF/​Qualitaetsstanda​rds/​QS_​Kolon_​Rektum_​V1.​0.​pdf. Accessed 11 Mar 2017

go back to reference Lugli A, Kirsch R, Ajioka Y, Bosman F, Cathomas G, Dawson H, El Zimaity H, Fléjou JF, Hansen TP, Hartmann A, Kakar S, Langner C, Nagtegaal I, Puppa G, Riddell R, Ristimäki A, Sheahan K, Smyrk T, Sugihara K, Terris B, Ueno H, Vieth M, Zlobec I, Quirke P (2017) Recommendations for reporting tumor budding in colorectal cancer based on the International Tumor Budding Consensus Conference (ITBCC) 2016. Mod Pathol 30:1299–1311. https://doi.org/10.1038/modpathol.2017.46 CrossRefPubMed Lugli A, Kirsch R, Ajioka Y, Bosman F, Cathomas G, Dawson H, El Zimaity H, Fléjou JF, Hansen TP, Hartmann A, Kakar S, Langner C, Nagtegaal I, Puppa G, Riddell R, Ristimäki A, Sheahan K, Smyrk T, Sugihara K, Terris B, Ueno H, Vieth M, Zlobec I, Quirke P (2017) Recommendations for reporting tumor budding in colorectal cancer based on the International Tumor Budding Consensus Conference (ITBCC) 2016. Mod Pathol 30:1299–1311. https://​doi.​org/​10.​1038/​modpathol.​2017.​46 CrossRefPubMed

go back to reference Koelzer VH, Zlobec I, Lugli A (2016) Tumor budding in colorectal cancer—ready for diagnostic practice? Hum Pathol 47:4–19. https://doi.org/10.1016/j.humpath.2015.08.007 CrossRefPubMed Koelzer VH, Zlobec I, Lugli A (2016) Tumor budding in colorectal cancer—ready for diagnostic practice? Hum Pathol 47:4–19. https://​doi.​org/​10.​1016/​j.​humpath.​2015.​08.​007 CrossRefPubMed

go back to reference Horcic M, Koelzer VH, Karamitopoulou E, Terracciano L, Puppa G, Zlobec I, Lugli A (2013) Tumor budding score based on 10 high-power fields is a promising basis for a standardized prognostic scoring system in stage II colorectal cancer. Hum Pathol 44:697–705. https://doi.org/10.1016/j.humpath.2012.07.026 CrossRefPubMed Horcic M, Koelzer VH, Karamitopoulou E, Terracciano L, Puppa G, Zlobec I, Lugli A (2013) Tumor budding score based on 10 high-power fields is a promising basis for a standardized prognostic scoring system in stage II colorectal cancer. Hum Pathol 44:697–705. https://​doi.​org/​10.​1016/​j.​humpath.​2012.​07.​026 CrossRefPubMed

go back to reference Dinnewitzer A, Jäger T, Nawara C, Buchner S, Wolfgang H, Öfner D (2013) Cumulative incidence of permanent stoma after sphincter preserving low anterior resection of mid and low rectal cancer. Dis Colon Rectum 56:1134–1142. https://doi.org/10.1097/DCR.0b013e31829ef472 CrossRefPubMed Dinnewitzer A, Jäger T, Nawara C, Buchner S, Wolfgang H, Öfner D (2013) Cumulative incidence of permanent stoma after sphincter preserving low anterior resection of mid and low rectal cancer. Dis Colon Rectum 56:1134–1142. https://​doi.​org/​10.​1097/​DCR.​0b013e31829ef472​ CrossRefPubMed

go back to reference Clark TG, Altman DG, De Stavola BL (2002) Quantification of the completeness of follow-up. Lancet 359:1309–1310. https://doi.org/10.1016/S0140-6736(02)08272-7 CrossRefPubMed Clark TG, Altman DG, De Stavola BL (2002) Quantification of the completeness of follow-up. Lancet 359:1309–1310. https://​doi.​org/​10.​1016/​S0140-6736(02)08272-7 CrossRefPubMed

go back to reference Mace AG, Pai RK, Stocchi L, Kalady MF (2015) American Joint Committee on Cancer and College of American Pathologists regression grade: a new prognostic factor in rectal cancer. Dis Colon Rectum 58:32–44. https://doi.org/10.1097/DCR.0000000000000266 CrossRefPubMed Mace AG, Pai RK, Stocchi L, Kalady MF (2015) American Joint Committee on Cancer and College of American Pathologists regression grade: a new prognostic factor in rectal cancer. Dis Colon Rectum 58:32–44. https://​doi.​org/​10.​1097/​DCR.​0000000000000266​ CrossRefPubMed

go back to reference Cao H, Xu E, Liu H, Wan L, Lai M (2015) Epithelial-mesenchymal transition in colorectal cancer metastasis: a system review. Pathol Res Pract 211:557–569. https://doi.org/10.1016/j.prp.2015.05.010 CrossRefPubMed Cao H, Xu E, Liu H, Wan L, Lai M (2015) Epithelial-mesenchymal transition in colorectal cancer metastasis: a system review. Pathol Res Pract 211:557–569. https://​doi.​org/​10.​1016/​j.​prp.​2015.​05.​010 CrossRefPubMed

go back to reference Kirchner T, Brabletz T (2000) Patterning and nuclear β‑Catenin expression in the colonic adenoma-carcinoma sequence: analogies with embryonic gastrulation. Am J Pathol 157:1113–1121. https://doi.org/10.1016/S0002-9440(10)64626-3 CrossRefPubMedCentralPubMed Kirchner T, Brabletz T (2000) Patterning and nuclear β‑Catenin expression in the colonic adenoma-carcinoma sequence: analogies with embryonic gastrulation. Am J Pathol 157:1113–1121. https://​doi.​org/​10.​1016/​S0002-9440(10)64626-3 CrossRefPubMedCentralPubMed

go back to reference Zlobec I, Lugli A (2010) Epithelial mesenchymal transition and tumor budding in aggressive colorectal cancer: tumor budding as oncotarget. Oncotarget 1:651–661. https://doi.org/10.18632/oncotarget.199 CrossRefPubMedCentralPubMed Zlobec I, Lugli A (2010) Epithelial mesenchymal transition and tumor budding in aggressive colorectal cancer: tumor budding as oncotarget. Oncotarget 1:651–661. https://​doi.​org/​10.​18632/​oncotarget.​199 CrossRefPubMedCentralPubMed

go back to reference Wang L, Zhang XM, Li Z, Liu XJ, Chai J, Zhang GY, Cheng YF (2013) Overexpression of nuclear β‑catenin in rectal adenocarcinoma is associated with radioresistance. World J Gastroenterol 19:6876–6882. https://doi.org/10.3748/wjg.v19.i40.6876 CrossRefPubMedCentralPubMed Wang L, Zhang XM, Li Z, Liu XJ, Chai J, Zhang GY, Cheng YF (2013) Overexpression of nuclear β‑catenin in rectal adenocarcinoma is associated with radioresistance. World J Gastroenterol 19:6876–6882. https://​doi.​org/​10.​3748/​wjg.​v19.​i40.​6876 CrossRefPubMedCentralPubMed

go back to reference Takahashi H, Nakamura K, Usami A, Tsuruta T, Hashimura M, Matsumoto T, Saegusa M (2017) Possible role of nuclear β‑catenin in resistance to preoperative chemoradiotherapy in locally advanced rectal cancer. Histopathology 71:227–237. https://doi.org/10.1111/his.13227 CrossRefPubMed Takahashi H, Nakamura K, Usami A, Tsuruta T, Hashimura M, Matsumoto T, Saegusa M (2017) Possible role of nuclear β‑catenin in resistance to preoperative chemoradiotherapy in locally advanced rectal cancer. Histopathology 71:227–237. https://​doi.​org/​10.​1111/​his.​13227 CrossRefPubMed

go back to reference Kawamoto A, Yokoe T, Tanaka K, Saigusa S, Toiyama Y, Yasuda H, Inoue Y, Miki C, Kusunoki M (2012) Radiation induces epithelial-mesenchymal transition in colorectal cancer cells. Oncol Rep 27:51–57. https://doi.org/10.3892/or.2011.1485 CrossRefPubMed Kawamoto A, Yokoe T, Tanaka K, Saigusa S, Toiyama Y, Yasuda H, Inoue Y, Miki C, Kusunoki M (2012) Radiation induces epithelial-mesenchymal transition in colorectal cancer cells. Oncol Rep 27:51–57. https://​doi.​org/​10.​3892/​or.​2011.​1485 CrossRefPubMed

go back to reference Tato-Costa J, Casimiro S, Pacheco T, Pires R, Fernandes A, Alho I, Pereira P, Costa P, Castelo HB, Ferreira J, Costa L (2016) Therapy-induced cellular senescence induces epithelial-to-mesenchymal transition and increases invasiveness in rectal cancer. Clin Colorectal Cancer 15:170–178.e3. https://doi.org/10.1016/j.clcc.2015.09.003 CrossRefPubMed Tato-Costa J, Casimiro S, Pacheco T, Pires R, Fernandes A, Alho I, Pereira P, Costa P, Castelo HB, Ferreira J, Costa L (2016) Therapy-induced cellular senescence induces epithelial-to-mesenchymal transition and increases invasiveness in rectal cancer. Clin Colorectal Cancer 15:170–178.e3. https://​doi.​org/​10.​1016/​j.​clcc.​2015.​09.​003 CrossRefPubMed

go back to reference Janjan NA, Khoo VS, Abbruzzese J, Pazdur R, Dubrow R, Cleary KR, Allen PK, Lynch PM, Glober G, Wolff R, Rich TA, Skibber J (1999) Tumor downstaging and sphincter preservation with preoperative chemoradiation in locally advanced rectal cancer: the M. D. Anderson Cancer Center experience. Int J Radiat Oncol Biol Phys 44:1027–1038. https://doi.org/10.1016/S0360-3016(99)00099-1 CrossRefPubMed Janjan NA, Khoo VS, Abbruzzese J, Pazdur R, Dubrow R, Cleary KR, Allen PK, Lynch PM, Glober G, Wolff R, Rich TA, Skibber J (1999) Tumor downstaging and sphincter preservation with preoperative chemoradiation in locally advanced rectal cancer: the M. D. Anderson Cancer Center experience. Int J Radiat Oncol Biol Phys 44:1027–1038. https://​doi.​org/​10.​1016/​S0360-3016(99)00099-1 CrossRefPubMed

go back to reference Medich D, McGinty J, Parda D, Karlovits S, Davis C, Caushaj P, Lembersky B (2001) Preoperative chemoradiotherapy and radical surgery for locally advanced distal rectal adenocarcinoma. Dis Colon Rectum 44:1123–1128. https://doi.org/10.1007/BF02234632 CrossRefPubMed Medich D, McGinty J, Parda D, Karlovits S, Davis C, Caushaj P, Lembersky B (2001) Preoperative chemoradiotherapy and radical surgery for locally advanced distal rectal adenocarcinoma. Dis Colon Rectum 44:1123–1128. https://​doi.​org/​10.​1007/​BF02234632 CrossRefPubMed

go back to reference Ueno H, Mochizuki H, Shinto E, Hashiguchi Y, Hase K, Talbot IC (2002) Histologic indices in biopsy specimens for estimating the probability of extended local spread in patients with rectal carcinoma. Cancer 94:2882–2891. https://doi.org/10.1002/cncr.10551 CrossRefPubMed Ueno H, Mochizuki H, Shinto E, Hashiguchi Y, Hase K, Talbot IC (2002) Histologic indices in biopsy specimens for estimating the probability of extended local spread in patients with rectal carcinoma. Cancer 94:2882–2891. https://​doi.​org/​10.​1002/​cncr.​10551 CrossRefPubMed

go back to reference Lugli A, Karamitopoulou E, Zlobec I (2012) Tumour budding: a promising parameter in colorectal cancer. Br J Cancer 106:1713–1717. https://doi.org/10.1038/bjc.2012.127 CrossRefPubMedCentralPubMed Lugli A, Karamitopoulou E, Zlobec I (2012) Tumour budding: a promising parameter in colorectal cancer. Br J Cancer 106:1713–1717. https://​doi.​org/​10.​1038/​bjc.​2012.​127 CrossRefPubMedCentralPubMed

go back to reference Karamitopoulou E, Zlobec I, Kölzer V, Kondi-Pafiti A, Patsouris ES, Gennatas K, Lugli A (2013) Proposal for a 10-high-power-fields scoring method for the assessment of tumor budding in colorectal cancer. Mod Pathol 26:295–301. https://doi.org/10.1038/modpathol.2012.155 CrossRefPubMed Karamitopoulou E, Zlobec I, Kölzer V, Kondi-Pafiti A, Patsouris ES, Gennatas K, Lugli A (2013) Proposal for a 10-high-power-fields scoring method for the assessment of tumor budding in colorectal cancer. Mod Pathol 26:295–301. https://​doi.​org/​10.​1038/​modpathol.​2012.​155 CrossRefPubMed

go back to reference Tranchart H, Lefèvre JH, Svrcek M, Flejou JF, Tiret E, Parc Y (2013) What is the incidence of metastatic lymph node involvement after significant pathologic response of primary tumor following neoadjuvant treatment for locally advanced rectal cancer? Ann Surg Oncol 20:1551–1559. https://doi.org/10.1245/s10434-012-2773-9 CrossRefPubMed Tranchart H, Lefèvre JH, Svrcek M, Flejou JF, Tiret E, Parc Y (2013) What is the incidence of metastatic lymph node involvement after significant pathologic response of primary tumor following neoadjuvant treatment for locally advanced rectal cancer? Ann Surg Oncol 20:1551–1559. https://​doi.​org/​10.​1245/​s10434-012-2773-9 CrossRefPubMed

go back to reference Rogers AC, Winter DC, Heeney A, Gibbons D, Lugli A, Puppa G, Sheahan K (2016) Systematic review and meta-analysis of the impact of tumour budding in colorectal cancer. Br J Cancer 115:831–840. https://doi.org/10.1038/bjc.2016.274 CrossRefPubMedCentralPubMed Rogers AC, Winter DC, Heeney A, Gibbons D, Lugli A, Puppa G, Sheahan K (2016) Systematic review and meta-analysis of the impact of tumour budding in colorectal cancer. Br J Cancer 115:831–840. https://​doi.​org/​10.​1038/​bjc.​2016.​274 CrossRefPubMedCentralPubMed

go back to reference Grigore AD, Jolly MK, Jia D, Farach-Carson MC, Levine H (2016) Tumor budding: the name is EMT. Partial EMT. J Clin Med 5(5).https://doi.org/10.3390/jcm5050051 CrossRefPubMedCentralPubMed Grigore AD, Jolly MK, Jia D, Farach-Carson MC, Levine H (2016) Tumor budding: the name is EMT. Partial EMT. J Clin Med 5(5).https://​doi.​org/​10.​3390/​jcm5050051 CrossRefPubMedCentralPubMed

go back to reference van Wyk HC, Park J, Roxburgh C, Horgan P, Foulis A, McMillan DC (2015) The role of tumour budding in predicting survival in patients with primary operable colorectal cancer: a systematic review. Cancer Treat Rev 41:151–159. https://doi.org/10.1016/j.ctrv.2014.12.007 CrossRefPubMed van Wyk HC, Park J, Roxburgh C, Horgan P, Foulis A, McMillan DC (2015) The role of tumour budding in predicting survival in patients with primary operable colorectal cancer: a systematic review. Cancer Treat Rev 41:151–159. https://​doi.​org/​10.​1016/​j.​ctrv.​2014.​12.​007 CrossRefPubMed

go back to reference Ohtsuki K, Koyama F, Tamura T, Enomoto Y, Fujii H, Mukogawa T, Nakagawa T, Uchimoto K, Nakamura S, Nonomura A, Nakajima Y (2008) Prognostic value of Immunohistochemical analysis of tumor budding in colorectal carcinoma. Anticancer Res 28:1831–1836PubMed Ohtsuki K, Koyama F, Tamura T, Enomoto Y, Fujii H, Mukogawa T, Nakagawa T, Uchimoto K, Nakamura S, Nonomura A, Nakajima Y (2008) Prognostic value of Immunohistochemical analysis of tumor budding in colorectal carcinoma. Anticancer Res 28:1831–1836PubMed

go back to reference Lugli A, Vlajnic T, Giger O, Karamitopoulou E, Patsouris ES, Peros G, Terracciano LM, Zlobec I (2011) Intratumoral budding as a potential parameter of tumor progression in mismatch repair-proficient and mismatch repair-deficient colorectal cancer patients. Hum Pathol 42:1833–1840. https://doi.org/10.1016/j.humpath.2011.02.010 CrossRefPubMed Lugli A, Vlajnic T, Giger O, Karamitopoulou E, Patsouris ES, Peros G, Terracciano LM, Zlobec I (2011) Intratumoral budding as a potential parameter of tumor progression in mismatch repair-proficient and mismatch repair-deficient colorectal cancer patients. Hum Pathol 42:1833–1840. https://​doi.​org/​10.​1016/​j.​humpath.​2011.​02.​010 CrossRefPubMed