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Evaluation of treatment response and tissue necrosis as prognostic indicators following neoadjuvant chemoradiotherapy in rectal cancer patients

  • Jung, Ji-Han (Department of Hospital Pathology, College of Medicine, The Catholic University of Korea) ;
  • An, Ho Jung (Department of Internal Medicine, College of Medicine, The Catholic University of Korea) ;
  • Kim, Hyung-Jin (Department of General Surgery, College of Medicine, The Catholic University of Korea) ;
  • Lee, Jonghoon (Department of Radiation Oncology, College of Medicine, The Catholic University of Korea) ;
  • Lee, Kang-Moon (Department of Internal Medicine, College of Medicine, The Catholic University of Korea) ;
  • Kim, Sung Hwan (Department of Radiation Oncology, College of Medicine, The Catholic University of Korea) ;
  • Cho, Hyeon-Min (Department of General Surgery, College of Medicine, The Catholic University of Korea) ;
  • Shim, Byoung Yong (Department of Internal Medicine, College of Medicine, The Catholic University of Korea)
  • Received : 2014.09.03
  • Accepted : 2014.12.05
  • Published : 2016.01.01

Abstract

Background/Aims: The objective of this study was to assess the prognostic roles of treatment response and tissue necrosis after chemoradiotherapy (CRT) in locally advanced rectal cancer. Methods: A total of 243 patients with locally advanced rectal cancer who underwent neoadjuvant CRT were included. Three treatment response groups were classified by their pathological stage results: complete treatment response (CTR), intermediate treatment response (ITR), and poor treatment response (PTR). Three tissue necrosis groups were classified based on tissue pathological results: complete necrosis response (CNR), intermediate necrosis response (INR), and poor necrosis response (PNR). Results: Overall survival (OS) and recurrence-free survival (RFS) rate at three years were 74.5% and 61.3%, respectively. The 3-year OS rates of the CTR, ITR, and PTR groups were 83.7%, 75.9%, and 69.7%, respectively (p < 0.001); the 3-year RFS rates were 76.7%, 69.0%, and 52.1%, respectively (p < 0.001). The 3-year OS rates of the CNR, INR, and PNR groups were 83.7%, 80.6%, and 61.8%, respectively (p < 0.001); the 3-year RFS rates were 76.7%, 68.9%, and 44.3%, respectively (p < 0.001). When compared to CTR/CNR, PTR/PNR was strongly related to an increased risk of recurrence (hazard ratio [HR], 5.53; 95% confidence interval [CI], 2.01 to 15.23 vs. HR, 6.37; 95% CI, 2.29 to 17.74, respectively) in univariate Cox regression. Both PTR and PNR were strongly associated with shorter RFS and OS when compared with CTR and CNR in the multivariate Cox regression. Conclusions: Tissue necrosis is an equally important prognostic marker as treatment response for oncologic outcomes in locally advanced rectal cancer.

Keywords

References

  1. Kockerling F, Reymond MA, Altendorf-Hofmann A, Dworak O, Hohenberger W. Influence of surgery on metachronous distant metastases and survival in rectal cancer. J Clin Oncol 1998;16:324-329. https://doi.org/10.1200/JCO.1998.16.1.324
  2. Nuyttens JJ, Robertson JM, Yan D, Martinez A. The influence of small bowel motion on both a conventional three-field and intensity modulated radiation therapy (IMRT) for rectal cancer. Cancer Radiother 2004;8:297-304. https://doi.org/10.1016/S1278-3218(04)00086-1
  3. Arbea L, Ramos LI, Martinez-Monge R, Moreno M, Aristu J. Intensity-modulated radiation therapy (IMRT) vs. 3D conformal radiotherapy (3DCRT) in locally advanced rectal cancer (LARC): dosimetric comparison and clinical implications. Radiat Oncol 2010;5:17. https://doi.org/10.1186/1748-717X-5-17
  4. Samuelian JM, Callister MD, Ashman JB, Young-Fadok TM, Borad MJ, Gunderson LL. Reduced acute bowel toxicity in patients treated with intensity-modulated radiotherapy for rectal cancer. Int J Radiat Oncol Biol Phys 2012;82:1981-1987. https://doi.org/10.1016/j.ijrobp.2011.01.051
  5. O'Connell JB, Maggard MA, Liu JH, Etzioni DA, Ko CY. Are survival rates different for young and older patients with rectal cancer? Dis Colon Rectum 2004;47:2064-2069. https://doi.org/10.1007/s10350-004-0738-1
  6. Rodel C, Liersch T, Becker H, et al. 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 2012;13:679-687. https://doi.org/10.1016/S1470-2045(12)70187-0
  7. Chua YJ, Barbachano Y, Cunningham D, et al. Neoadjuvant capecitabine and oxaliplatin before chemoradiotherapy and total mesorectal excision in MRI-defined poor-risk rectal cancer: a phase 2 trial. Lancet Oncol 2010;11:241-248. https://doi.org/10.1016/S1470-2045(09)70381-X
  8. Klautke G, Feyerherd P, Ludwig K, Prall F, Foitzik T, Fietkau R. Intensified concurrent chemoradiotherapy with 5-fluorouracil and irinotecan as neoadjuvant treatment in patients with locally advanced rectal cancer. Br J Cancer 2005;92:1215-1220. https://doi.org/10.1038/sj.bjc.6602492
  9. Silberfein EJ, Kattepogu KM, Hu CY, et al. Long-term survival and recurrence outcomes following surgery for distal rectal cancer. Ann Surg Oncol 2010;17:2863-2869. https://doi.org/10.1245/s10434-010-1119-8
  10. Park IJ, You YN, Agarwal A, et al. Neoadjuvant treatment response as an early response indicator for patients with rectal cancer. J Clin Oncol 2012;30:1770-1776. https://doi.org/10.1200/JCO.2011.39.7901
  11. Rodel C, Martus P, Papadoupolos T, et al. Prognostic significance of tumor regression after preoperative chemoradiotherapy for rectal cancer. J Clin Oncol 2005;23:8688-8696. https://doi.org/10.1200/JCO.2005.02.1329
  12. Maas M, Nelemans PJ, Valentini V, et al. Long-term outcome in patients with a pathological complete response after chemoradiation for rectal cancer: a pooled analysis of individual patient data. Lancet Oncol 2010;11:835-844. https://doi.org/10.1016/S1470-2045(10)70172-8
  13. Santos MD, Silva C, Rocha A, Matos E, Nogueira C, Lopes C. Prognostic value of mandard and dworak tumor regression grading in rectal cancer: study of a single tertiary center. ISRN Surg 2014;2014:310542.
  14. Capirci C, Valentini V, Cionini L, et al. Prognostic value of pathologic complete response after neoadjuvant therapy in locally advanced rectal cancer: long-term analysis of 566 ypCR patients. Int J Radiat Oncol Biol Phys 2008;72:99-107. https://doi.org/10.1016/j.ijrobp.2007.12.019
  15. Breugom AJ, van den Broek CB, van Gijn W, et al. The value of adjuvant chemotherapy in rectal cancer patients after preoperative radiotherapy or chemoradiation followed by TME-surgery: the PROCTOR/SCRIPT study. Eur J Cancer 2013;49(Suppl 3):S1.
  16. Cionini L, Sainato A, De Paoli A, et al. Final results of randomized trial on adjuvant chemotherapy after preoperative chemoradiation in rectal cancer. Radiother Oncol 2010;96(Suppl 1):S113-S114.
  17. Bosset JF, Calais G, Mineur L, et al. Fluorouracil-based adjuvant chemotherapy after preoperative chemoradiotherapy in rectal cancer: long-term results of the EORTC 22921 randomised study. Lancet Oncol 2014;15:184-190. https://doi.org/10.1016/S1470-2045(13)70599-0
  18. Hong YS, Nam BH, Kim KP, et al. 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 2014;15:1245-1253. https://doi.org/10.1016/S1470-2045(14)70377-8