Strahlentherapie und Onkologie

, Volume 190, Issue 6, pp 515–520 | Cite as

Complete pathological responses in locally advanced rectal cancer after preoperative IMRT and integrated-boost chemoradiation

  • Ovidio Hernando-Requejo
  • Mercedes López
  • Antonio Cubillo
  • Almudena Rodriguez
  • Raquel Ciervide
  • Jeannette Valero
  • Emilio Sánchez
  • Mariola Garcia-Aranda
  • Jesus Rodriguez
  • Guillermo Potdevin
  • Carmen Rubio
Original article


Background and purpose

To analyze the efficacy and safety of a new preoperative intensity-modulated radiotherapy (IMRT) and integrated-boost chemoradiation scheme.

Patients and methods

In all, 74 patients were treated with IMRT and concurrent standard dose capecitabine. The dose of the planning target volume (PTV) encompassing the tumor, mesorectum, and pelvic lymph nodes was 46 Gy in 23 fractions; the boost PTV, at a dose of 57.5 Gy in 23 fractions, included the macroscopic primary tumor and pathological lymph nodes. The patients underwent surgery 6–8 weeks after chemoradiation.


The complete treatment data of 72 patients were analyzed. Tumor downstaging was achieved in 55 patients (76.38 %) and node downstaging in 34 (47.2 %). In 22 patients (30.6 %), there was complete pathological response (ypCR). The circumferential resection margin was free of tumor in 70 patients (97.2 %). The 3-year estimated overall survival and disease-free survival rates were 95.4 and 85.9 % respectively, and no local relapse was found; however, ten patients (13.8 %) developed distant metastases. High pathologic tumor (pT) downstaging was shown as a favorable prognostic factor for disease-free survival. No grade 4 acute radiotherapy-related toxicity was found.


The IMRT and integrated-boost chemoradiation scheme offered higher rates of ypCR and pT downstaging, without a significant increase in toxicity. The circumferential margins were free of tumors in the majority of patients. Primary tumor regression was associated with better disease-free survival.


Rectal carcinoma Chemoradiation Intensity-modulated radiotherapy Downstaging Pathological complete response 

Komplette pathologische Remissionen bei lokal fortgeschrittenem Rektalkarzinom nach präoperativer IMRT- und integrierter Boost-Radiochemotherapie


Hintergrund und Ziel

Analyse von Wirksamkeit und Sicherheit eines neuen präoperativen intensitätsmodulierten Bestrahlungsschemas (IMRT) mit integriertem Boost.

Patienten und Methodik

Insgesamt 74 Patienten wurden simultan mit IMRT und Capecitabin (Standarddosis) behandelt. Die Dosis des Planungszielvolumens (PTV) umfasste den Tumor, das Mesorektum sowie die Beckenlymphknoten und betrug 46 Gy in 23 Fraktionen. Das Boost-PTV betrug 57,5 Gy in 23 Fraktionen und umfasste den makroskopischen Primärtumor und die erkrankten Lymphknoten. Die Patienten wurden 6–8 Wochen nach der Radiochemotherapie operiert.


Es wurden die vollständigen Behandlungsdaten von 72 Patienten analysiert. Ein Tumor-Downstaging zeigten 55 Patienten (76,38 %) und ein Lymphknoten-Downstaging 34 Patienten (47,2 %). Ein vollständiger Rückgang des Tumors (pCR) war bei 22 Patienten zu beobachten (30,6 %). Der tumorumgebende Resektionsrand war bei 70 Patienten tumorfrei (97,2 %). Das allgemeine 3-Jahres-Überleben und das krankheitsfreie Überleben lagen jeweils bei 95,4 bzw. 85,9 %. Lokalrezidive traten nicht ein, jedoch haben sich bei 10 Patienten Fernmetastasen entwickelt (13,8 %). Ein Primärtumor-Downstaging wirkte sich positiv auf die Prognose bezüglich eines krankheitsfreien Überlebens aus. Es wurde keine Grad-4-Toxizität beobachtet.


Das untersuchte IMRT-Bestrahlungsschema mit integriertem Boost zeigt eine höhere Wahrscheinlichkeit einer vollständigen Rückbildung und eines pathologischen Downstagings ohne wesentliche Toxizitätserhöhung. Der umgebende Resektionsrand war bei den meisten Patienten tumorfrei. Die beobachtete Primärtumorregression wurde mit besseren krankheitsfreien Überlebenschancen in Zusammenhang gebracht.


Rektumkarzinom Strahlenchemotherapie Intensitätsmodulierte Strahlentherapie Downstaging Pathologisch vollständige Remission 


Compliance with ethical guidelines

Conflict of interest

O. Hernando-Requejo, M. López, A. Cubillo, A. Rodriguez, R. Ciervide, J. Valero, E. Sánchez, M. Garcia-Aranda, J. Rodriguez, G. Potdevin, and C. Rubio state that there are no conflicts of interest.


  1. 1.
    Nelson H, Petrelli N, Carlin A et al (2001) Guidelines 2000 for colon and rectal cancer surgery. J Natl Cancer Inst 93:583–596PubMedCrossRefGoogle Scholar
  2. 2.
    Jemal A, Siegel R, Ward E et al (2008) Cancer statistics, 2008. CA Cancer J Clin 58:71–96PubMedCrossRefGoogle Scholar
  3. 3.
    Sauer R, Becker H, Hohenberger W et al (2004) Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med 351:1731–1740PubMedCrossRefGoogle Scholar
  4. 4.
    Rödel C, Martus P, Papadopoulos T et al (2005) Prognostic significance of tumor regresión after preoperative chemoradiotherapy for rectal cáncer. J ClinOncol 23:8688–8696CrossRefGoogle Scholar
  5. 5.
    Kim TH, Chang HJ, Kim DY et al (2010) Pathological nodal classification is the most discriminating prognostic factor for disease-free survival in rectal cáncer patients treated with preoperative chemoradiotherapy and curative resection. Int J Radiat Oncol Biol Phys 77:1158–1165PubMedCrossRefGoogle Scholar
  6. 6.
    Lee JH, Kim SH, Kim JG et al (2011) Preoperative chemoradiotherapy (CRT) followed by laparoscopic surgery for rectal cancer: predictors of the tumor response and the long-term oncologic outcomes. Int J Radiat Oncol Biol Phys 82:431e438Google Scholar
  7. 7.
    Bosset JF, Collette L, Calais G et al (2006) Chemotherapy with preoperative radiotherapy in rectal cancer. N Eng J Med 355:1114–1123CrossRefGoogle Scholar
  8. 8.
    Bosset JF, Magnin V, Maingon P et al (2000) Preoperative radiochemotherapy in rectal cancer: long-term results of a Phase II trial. Int J Rad Oncol Biol Phys 46:323–327CrossRefGoogle Scholar
  9. 9.
    Rödel C, Grabenbauer GG, Papadopoulos T et al (2003) Phase I-II trial of capecitabine, oxaliplatin and radiation for rectal cancer. J Clin Oncol 21:3098–3104PubMedCrossRefGoogle Scholar
  10. 10.
    Machiels JP, Duck L, Honhon B et al (2005) Phase II study of preoperative oxaliplatin, capecitabine and external beam radiotherapy in patients with rectal cancer. The RadiOxCape study. Ann Oncol 16:1898–1905PubMedCrossRefGoogle Scholar
  11. 11.
    Hospers GA, Punt CJ, Tesselaar ME et al (2007) Preoperative chemoradiotherapy with capecitabine and oxaliplatin in locally advanced rectal cancer. A phase I-II multicenter study of the Duch Colorectal Cancer Group. Ann SurgOncol 14:2773–2779Google Scholar
  12. 12.
    Gerard JP, Azria D, Gourgou-Bourgade S et al (2010) Comparison of two neoadjuvant chemoradiotherapy regimens for locally advanced rectal cancer. Results of the Phase III trial ACCORD 12/0405-Prodige 2. J ClinOncol 28:1638–1644CrossRefGoogle Scholar
  13. 13.
    Winkler J, Zipp L, Knoblich J et al (2012) Simultaneous neoadjuvant radiochemotherapy with capecitabine and oxaliplatin for locally advanced rectal cancer. Strahlentherapie und Onkologie 188:377–382PubMedCrossRefGoogle Scholar
  14. 14.
    Rödel C, Liersch T, Hermann RM et al (2007) Multicenter phase II trial of chemoradiation with oxaliplatin for rectal cancer. J ClinOncol 25 110–117CrossRefGoogle Scholar
  15. 15.
    Aschele CP, Cordio S, Rosati G et al (2009) Preoperative fluorouracil (FU)-based chemoradiation with and without weekly oxaliplatin in locally advanced rectal cancer: pathologic response analysis of the Studio Terapia Adiuvante Retto (STAR)-01 randomized phase III trial. J Clin Oncol 27(suppl): 170s, abstr CRA4008Google Scholar
  16. 16.
    Fu KK, Pajak TF, Trotti A et al (2000) A Radiation Therapy Oncology Group (RTOG) phase III randomized study to compare hyperfractionation and two variants of accelerated fractionation to standard fractionation radiotherapy for head and neck squamous cell carcinomas: first report of RTOG 9003. Int J Radiat Oncol Biol Phys 48:7–16PubMedCrossRefGoogle Scholar
  17. 17.
    Kim DY, Kim TH, Jung KH et al (2006) Preoperative chemoradiotherapy with concomitant small field boost irradiation for locally advanced rectal cancer: a multi-institutional phase II study (KROG 04-01). Dis Colon Rectum 49:1684–1691PubMedCrossRefGoogle Scholar
  18. 18.
    Jong Hoon Lee, Dae Yong Kim, Taek-Keun Nam et al (2012) Long-term follow-up of preoperative pelvic radiation therapy and concomitant boost irradiation in locally advanced rectal cancer patients: a multi-institutional phase II study (KROG 04-01) Int J Radiat Oncol Biol Phys 84:955–961CrossRefGoogle Scholar
  19. 19.
    Cubillo A, Hernando-Requejo O, Garcia-Garcia E et al (2014) A prospective pilot study of target-guided personalized chemotherapy with intensity-modulated radiotherapy in patients with early rectal cancer. AM J Clin Oncol 37:117–121Google Scholar
  20. 20.
    Freedman GM, Meropol NJ, Sigurdson ER et al (2007) Phase I trial of preoperative hypofractionated intensity-modulated radiotherapy with incorporated boost and oral capecitabine in locally advanced rectal cancer. Int J Radiat Oncol Biol Phys 67:1389–1393PubMedCrossRefGoogle Scholar
  21. 21.
    Jin-luan Li, Jia-fu Ji, Xiao-fan Li et al (2012) Preoperative concomitant boost intensity-modulated radiotherapy with oral capecitabine in locally advanced mid-low rectal cancer: a phase II trial. Radiother Oncol 102:4–9CrossRefGoogle Scholar
  22. 22.
    Chua YJ, Barbachano Y, Cunningham D et al (2010) Neoadjuvant capecitabine and oxaliplatin before chemoradiotherapy and total mesorectal excision in MRIdefined poor-risk rectal cancer: a phase 2 trial. Lancet Oncol 11:241–248PubMedCrossRefGoogle Scholar
  23. 23.
    Ballonoff A, Kavanagh B, McCarter M et al (2008) Preoperative capecitabine and accelerated intensity-modulated radiotherapy in locally advanced rectal cancer: a phase II trial. Am J Clin Oncol 31:264–270PubMedCrossRefGoogle Scholar
  24. 24.
    De Paoli A, Chiara, Luppi G et al (2006) Capecitabine in combination with preoperative radiation therapy in locally advanced, resectable, rectal cancer: multicentric phase II study. Ann Oncol 17:246–251PubMedCrossRefGoogle Scholar
  25. 25.
    Debucquoy A, Roels S, Goethals L et al (2009) Double blind randomized phase II study with radiation + 5-fluorouracil ± celecoxib for resectable rectal cancer. Radiother Oncol 93:273–278PubMedCrossRefGoogle Scholar
  26. 26.
    Francois Y, Nemoz CJ, Baulieux J et al (1999) Influence of the interval between preoperative radiation therapy and surgery on downstaging and on the rate of sphincter-sparing surgery for rectal cancer: the Lyon R90-01 randomized trial. J Clin Oncol 17:2396PubMedGoogle Scholar
  27. 27.
    Pettersson D, Cedermark B, Holm T et al (2010) Interim analysis of the Stockholm III trial of preoperative radiotherapy regimens for rectal cancer. Br J Surg 97:580–587PubMedCrossRefGoogle Scholar
  28. 28.
    Glynne-Jonnes R, Mawdsley S et al (2006) Alternative clinical endpoints in rectal cancer- are we getting closer? Ann Oncol 17:1239–1248CrossRefGoogle Scholar
  29. 29.
    Dekker JW, Peeters KC, Putter H et al (2010) Metastatic lymph node ratio in stage III rectal cancer: prognostic significance in addition to the 7th edition of the TNM classification. Eur J Surg Oncol 36:1180–1186CrossRefGoogle Scholar
  30. 30.
    Medical research Council Rectal Cancer Working Party (1996) Randomised trial of surgery versus radiotherapy followed by surgery for potentially operable advanced rectal cáncer. Lancet 348:1605–1610CrossRefGoogle Scholar
  31. 31.
    Mawdsley S, Glynne-Jones R, Grainger J et al (2005) Can the histopathological assessment of the circumferential margin following pre-operative pelvic chemo-radiotherapy for T3/4 rectal cancer predict for three year disease free survival? Int J Radiation Oncol Biol Phys 63:745–752CrossRefGoogle Scholar
  32. 32.
    Sautter-Bihl ML, Hohenberger W, Fietkau R et al (2013) Rectal cancer. Strahlentherapie und Onkologie 189:105–110PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Ovidio Hernando-Requejo
    • 1
    • 3
    • 4
  • Mercedes López
    • 1
  • Antonio Cubillo
    • 2
    • 3
  • Almudena Rodriguez
    • 1
  • Raquel Ciervide
    • 1
  • Jeannette Valero
    • 1
  • Emilio Sánchez
    • 1
  • Mariola Garcia-Aranda
    • 1
  • Jesus Rodriguez
    • 2
    • 3
  • Guillermo Potdevin
    • 1
  • Carmen Rubio
    • 1
    • 3
  1. 1.Department of Radiation OncologyHospital Universitario SanchinarroMadridSpain
  2. 2.Department of Medical OncologyHospital Universitario SanchinarroMadridSpain
  3. 3.CEU San Pablo UniversityHospital Universitario SanchinarroMadridSpain
  4. 4.Centro Integral Oncológico Clara CampalHM Universitario SanchinarroMadridSpain

Personalised recommendations