The potential benefit of adjuvant chemotherapy in locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy is not predicted by tumor regression grade
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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.
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.
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.
KeywordsRectal cancer Neoadjuvant chemoradiotherapy Tumor regression grade Dworak Overall survival Disease-free survival
We would like to acknowledge Dr. Mariana Brandao (MD) for her help with statistical analysis, and for her support and encouragement to write the manuscript. We would like to acknowledge the contribution of a medical writer, Sandy Field, PhD, for preparation and formatting of this manuscript.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflicts of interest.
- 3.Dutch guideline colorectal cancer versie 3.0. http://www.oncoline.nl/colorectaalcarcinoom (updated 2014-04-16)
- 4.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)
- 7.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 32:1554–1562CrossRefPubMedGoogle Scholar
- 8.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:e2272Google Scholar
- 10.Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A (eds) (2010) AJCC Cancer staging manual, 7th edn. Springer, New YorkGoogle Scholar
- 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:CD004078Google Scholar
- 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 25:1356–1362CrossRefPubMedGoogle Scholar
- 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 26:696–701CrossRefPubMedGoogle Scholar
- 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 25:4379–4386CrossRefPubMedGoogle Scholar
- 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 15:184–190CrossRefPubMedGoogle Scholar
- 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 92:540–547CrossRefPubMedGoogle Scholar
- 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 17:615CrossRefPubMedPubMedCentralGoogle Scholar
- 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 15:1245–1253CrossRefPubMedGoogle Scholar