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International Journal of Colorectal Disease

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01-10-2018 | Original Article

The potential benefit of adjuvant chemotherapy in locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy is not predicted by tumor regression grade

Authors: Ali Bohlok, Alain Hendlisz, Fikri Bouazza, Maria Gomez Galdon, Jean Van de Stadt, Luigi Moretti, Issam El Nakadi, Gabriel Liberale

Published in: International Journal of Colorectal Disease | Issue 10/2018

Abstract

Introduction

Recommended treatment for locally advanced rectal cancer (LARC) is neoadjuvant chemoradiotherapy (NACRT) followed by surgery and total mesorectal excision (TME). The role of adjuvant chemotherapy (ACT) in this regimen is still debated. Assessment of Dworak’s tumor regression grade (TRG) after NACRT could potentially select patients who might benefit from ACT.

Materials and methods

Data for patients who underwent NACRT and TME for LARC between 2007 and 2014 were retrieved from the Bordet Institute database. Overall survival (OS) and disease-free survival (DFS) were calculated for the whole population, according to whether or not they received ACT, and according to TRG.

Results

We included 74 patients (38 males) with a median age of 62.7 years (33–84 years). AJCC stage cIIIb disease was the most frequent (73%). Pathologic complete response (pCR) was achieved in 13 patients (17.6%). ACT was administered to 42 patients (56.8%). Five-year OS and DFS of patients who received ACT or not were 92 and 84.5% (p = ns), and 79.9 and 84.8% (p = ns), respectively. OS was related to TRG (cut-off value of 3) (p = 0.001). ACT administration was not correlated with improved outcomes in any TRG groups.

Conclusion

TRG is a prognostic factor for both OS and DFS but does not appear to have a significant benefit for the selection of patients with LARC treated with NACRT who might benefit from the administration of ACT. Prospective randomized trials with larger populations are needed to identify factors that predict which patients may benefit from the administration of ACT.

Siegel RL, Miller KD, Jemal A (2017) Cancer statistics, 2017. CA Cancer J Clin 67:7–30CrossRefPubMed

Bufalari A, Boselli C, Giustozzi G, Moggi L (2000) Locally advanced rectal cancer: a multivariate analysis of outcome risk factors. J Surg Oncol 74:2–10CrossRefPubMed

Dutch guideline colorectal cancer versie 3.0. http://www.oncoline.nl/colorectaalcarcinoom (updated 2014-04-16)

Rectal cancer, NCCN clinical practice guidelines in oncology, Version I; 2017. http://www.nccn.org/professionals/physician_gls/pdf/rectal. pdf. (accessed 12 March 2018)

Glynne-Jones R, Wyrwicz L, Tiret E, Brown G, Rödel C, Cervantes A, Arnold D, ESMO Guidelines Committee (2017) Rectal cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 28(suppl_4):iv22–iv40CrossRefPubMed

Gash KJ, Baser O, Kiran RP (2017) Factors associated with degree of tumour response to neo-adjuvant radiotherapy in rectal cancer and subsequent corresponding outcomes. Eur J Surg Oncol 43:2052–2059CrossRefPubMed

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 32:1554–1562CrossRefPubMed

Zhang LN, Xiao WW, Xi SY, OuYang PY, You KY, Zeng ZF et al (2016) Pathological assessment of the AJCC tumor regression grading system after preoperative chemoradiotherapy for Chinese locally advanced rectal cancer. Wall Medicine 95:e2272

Rodel C, Martus P, Papadoupolos T, Füzesi L, Klimpfinger M, Fietkau R et al (2005) Prognostic significance of tumor regression after preoperative chemoradiotherapy for rectal cancer. J Clin Oncol 23:8688–8696CrossRefPubMed

10.

Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A (eds) (2010) AJCC Cancer staging manual, 7th edn. Springer, New York

11.

Dworak O, Keilholz L, Hoffmann A (1997) Pathological features of rectal cancer after preoperative radiochemotherapy. Int J Color Dis 12:19–23CrossRef

12.

Petersen SH, Harling H, Kirkeby LT, Wille-Jørgensen P, Mocellin S (2012) Postoperative adjuvant chemotherapy in rectal cancer operated for cure. Cochrane Database Syst Rev 3:CD004078

13.

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 with rectal cancer. N Engl J Med 355:1114–1123CrossRefPubMed

14.

Glynne-Jones R, Counsell N, Quirke P, Mortensen N, Maraveyas A, Meadows HMJ et al (2014) Chronicle: results of a randomised phase III trial in locally advanced rectal cancer after neoadjuvant chemoradiation randomising postoperative adjuvant capecitabine plus oxaliplatin (XELOX) versus control. Ann Oncol 25:1356–1362CrossRefPubMed

15.

Breugom AJ, van Gijn W, Muller EW, Berglund A, van den Broek CBM, Fokstuen T, Gelderblom H, Kapiteijn E, Leer JWH, Marijnen CAM, Martijn H, Meershoek-Klein Kranenbarg E, Nagtegaal ID, Pahlman L, Punt CJA, Putter H, Roodvoets AGH, Rutten HJT, Steup WH, Glimelius B, van de Velde CJH, Cooperative Investigators of the Dutch Colorectal Cancer Group and the Nordic Gastrointestinal Tumour Adjuvant Therapy Group (2015) Adjuvant chemotherapy for rectal cancer patients treated with preoperative (chemo)radiotherapy and total mesorectal excision: a Dutch Colorectal Cancer Group (DCCG) randomized phase III trial. Ann Oncol 26:696–701CrossRefPubMed

16.

Collette L, Bosset JF, den Dulk M, Nguyen F, Mineur L, Maingon P, Radosevic-Jelic L, Piérart M, Calais G, European Organisation for Research and Treatment of Cancer Radiation Oncology Group (2007) 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 EORTC Radiation Oncology Group. J Clin Oncol 25:4379–4386CrossRefPubMed

17.

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 J, 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 15:184–190CrossRefPubMed

18.

Park IJ, Kim DY, Kim HC, Kim NK, Kim HR, Kang SB, Choi GS, Lee KY, Kim SH, Oh ST, Lim SB, Kim JC, Oh JH, Kim SY, Lee WY, Lee JB, Yu CS (2015) Role of adjuvant chemotherapy in ypT0-2N0 patients treated with preoperative chemoradiation therapy and radical resection for rectal cancer. Int J Radiat Oncol Biol Phys 92:540–547CrossRefPubMed

19.

Huh JW, Kim HR (2009) Postoperative chemotherapy after neoadjuvant chemoradiation and surgery for rectal cancer: is it essential for patients with ypT0-2N0? J Surg Oncol 100:387–391CrossRefPubMed

20.

Kim CG, Ahn JB, Shin SJ, Beom SH, Heo SJ, Park HS, Kim JH, Choe EA, Koom WS, Hur H, Min BS, Kim NK, Kim H, Kim C, Jung I, Jung M (2017) Role of adjuvant chemotherapy in locally advanced rectal cancer with ypT0-3N0 after preoperative chemoradiation therapy and surgery. BMC Cancer 17:615CrossRefPubMedPubMedCentral

21.

Maas M, Nelemans PJ, Valentini V, Crane CH, Capirci C, Rodel C et al (2015) Adjuvant chemotherapy in rectal cancer: defining subgroups who may benefit after neoadjuvant chemoradiation and resection—a pooled analysis. Int J Cancer 137:212–220CrossRefPubMed

22.

Hong YS, Nam BH, Kim KP, Kim JE, Park SJ, Park YS, Park JO, Kim SY, Kim TY, Kim JH, Ahn JB, Lim SB, Yu CS, Kim JC, Yun SH, Kim JH, Park JH, Park HC, Jung KH, Kim TW (2014) Oxaliplatin, fluorouracil, and leucovorin versus fluorouracil and leucovorin as adjuvant chemotherapy for locally advanced rectal cancer after preoperative chemoradiotherapy (ADORE): an open-label, multicentre, phase 2, randomised controlled trial. Lancet Oncol 15:1245–1253CrossRefPubMed

Title: The potential benefit of adjuvant chemotherapy in locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy is not predicted by tumor regression grade
Authors: Ali Bohlok
Alain Hendlisz
Fikri Bouazza
Maria Gomez Galdon
Jean Van de Stadt
Luigi Moretti
Issam El Nakadi
Gabriel Liberale
Publication date: 01-10-2018
Publisher: Springer Berlin Heidelberg
Published in: International Journal of Colorectal Disease / Issue 10/2018
Print ISSN: 0179-1958
Electronic ISSN: 1432-1262
DOI: https://doi.org/10.1007/s00384-018-3115-6

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The potential benefit of adjuvant chemotherapy in locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy is not predicted by tumor regression grade

Abstract

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Materials and methods

Results

Conclusion

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