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Signet ring cell histology and non-circumferential tumors predict pathological complete response following neoadjuvant chemoradiation in rectal cancers

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International Journal of Colorectal Disease Aims and scope Submit manuscript

Abstract

Purpose

Neoadjuvant chemoradiation followed by surgery is now the standard of care for patients with locally advanced rectal cancers. The aim of this study was to determine the rate of pathological complete response (pCR) following neoadjuvant treatment in patients with rectal cancers and identify the factors predicting the same.

Methods

We conducted a retrospective analysis of patients with rectal cancers treated with neoadjuvant therapy followed by surgery at our institution from 1993 to 2008. Patients who achieved pCR were identified. Various patient, tumor, and treatment-related factors were studied for their influence on pCR by univariate and multivariate analyses. The influence of pCR on survival was also studied but was restricted to patients with a minimum follow-up of 5 years.

Results

Between 1993 and 2008, 248 patients with rectal cancers received neoadjuvant therapy followed by surgery. Two hundred and twenty-seven patients received chemoradiation and 21 patients received only radiation. Pathological complete response was seen in 32 patients (12.9%). On multivariate analysis, the factors found to be independently predictive of pathological response were circumferential extent of the primary tumor (p = 0.016) and signet ring cell histology (p = 0.001). Among 116 patients with a minimum follow-up of 5 years, there was a trend towards increased overall survival (75% versus 54%) and reduced local recurrence (6.2%versus 12.3%) in the 16 patients who achieved a pCR compared to those who did not, even though the difference was not statistically significant.

Conclusions

The factors that predict a pCR after neoadjuvant treatment for rectal cancers are absence of circumferential involvement and signet ring cell histology. Pathological complete response may confer an insignificant survival advantage.

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References

  1. Sauer R, Becker H, Hohenberger W, Rodel C, Wittekind C, Fietkau R et al (2004) Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med 351:1731–1740

    Article  CAS  PubMed  Google Scholar 

  2. Roh MS, Colangelo LH, O’Connell MJ, Yothers G, Deutsch M, Allegre CJ et al (2009) Preoperative multimodality therapy improves disease-free survival in patients with carcinoma of the rectum: NSABP R-03. J Clin Oncol 27:5124–5130

    Article  PubMed  Google Scholar 

  3. Gerard JP, Conroy T, Bonnetain F, Bouche O, Chapet O, Closon-Dejardin MT et al (2006) Preoperative radiotherapy with or without concurrent fluorouracil and leucovorin in T3-T4 rectal cancers: results of FFCD 9203. J Clin Oncol 24:4620–4625

    Article  PubMed  Google Scholar 

  4. Bosset JF, Calais G, Mineur L, Maingon P, Radosevic-Jelic L, Daban A et al (2005) Enhanced tumoricidal effect of chemotherapy with preoperative radiotherapy for rectal cancer: preliminary results of EORTC 22921. J Clin Oncol 23:5620–5627

    Article  CAS  PubMed  Google Scholar 

  5. Shanta V, Swaminathan R, Rama R, Radhika R (2008) Retrospective analysis of locally advanced non inflammatory breast cancer from Chennai, South India, 1990–1999. Int J Radiation Oncology Biol Phys 70:51–58

    Article  Google Scholar 

  6. Donington JS, Miller DL, Allen MS, Deschamps C, Nichols FC 3rd, Pairolero PC (2003) Tumor response to induction chemoradiation: influence on survival after esophagectomy. Eur J Cardiothorac Surg 24:631–636

    Article  PubMed  Google Scholar 

  7. Caprici C, Valentini V, Cionini L, De Paoli A, Rodel C, Glynne-Jones R et al (2008) Prognostic value of pathologic complete response after neoadjuvant therapy in locally advanced rectal cancer: long-term analysis of 566 ypCR patients. Int J Radiation Oncology Biol Phys 72:99–107

    Article  Google Scholar 

  8. Quirke P, Durdey P, Dixon MF, Williams NS (1986) Local recurrence of rectal adenocarcinoma due to inadequate surgical resection: histological study of lateral tumor spread and surgical excision. Lancet ii:996–999

    Article  Google Scholar 

  9. Hamilton SR, Vogelstein B, Kudo S, Riboli E, Nakamura S, Hainaut P et al (2000) Carcinoma of the colon and rectum. In: Hamilton SR, Aaltonen LA (eds) World Health Organization classification of tumors. Pathology and genetics of tumors of the digestive system. IARC, Lyon, p 109

    Google Scholar 

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

    Article  CAS  Google Scholar 

  11. Wheeler JM, Warren BF, Mortensen NJ, Ekanyaka N, Kulacoglu H, Jones A et al (2002) Quantification of histological regression of rectal cancer after irradiation: a proposal for a modified staging system. Dis Colon Rectum 45:1051–1056

    Article  CAS  PubMed  Google Scholar 

  12. Shia J, Guillem JG, Moore HG, Tickoo SK, Qin J, Ruo L et al (2004) Patterns of morphological alterations in residual rectal carcinoma following preoperative chemoradiotherapy and their association with long-term outcome. Am J Surg Pathol 28:215–223

    Article  PubMed  Google Scholar 

  13. Beddy D, Hyland P, Winter DC, Lim C, White A, Moriarty M et al (2008) A simplified Tumor Regression Grade correlates with survival in locally advanced rectal carcinoma treated with neoadjuvant chemoradiotherapy. Ann Surgl Oncol 15:3471–3477

    Article  CAS  Google Scholar 

  14. Hartley A, Ho KF, Mc Conkey C, Geh JI (2005) Pathological complete response following pre-operative chemoradiotherapy in rectal cancer: analysis of phase II/III trials. Br J Radiol 78:934–938

    Article  CAS  PubMed  Google Scholar 

  15. Das P, Skibber JM, Rodriguez-Bigas MA, Feig BW, Chang GJ, Wolff RA et al (2007) Predictors of tumor response and downstaging in patients who receive preoperative chemoradiation for rectal cancer. Cancer 109:1750–1755

    Article  CAS  PubMed  Google Scholar 

  16. Grillo-Ruggieri F, Mantello G, Berardi R, Cardinali M, Fenu F, Iovini G et al (2007) Mucinous rectal adenocarcinoma can be associated to tumor downstaging after preoperative chemotherapy. Dis Colon Rectum 50:1594–1603

    Article  PubMed  Google Scholar 

  17. Stein DE, Mahmoud NN, Anne PR, Rose DG, Isenberg GA, Goldstein SD et al (2003) Longer time interval between completion of neoadjuvant chemoradiation and surgical resection does not improve downstaging of rectal carcinoma. Dis Colon Rectum 46:448–453

    Article  PubMed  Google Scholar 

  18. Moore HG, Gittleman AE, Minsky BD, Wong D, Paty PB, Weiser M et al (2004) Rate of pathologic complete response with increased interval between preoperative combined modality therapy and rectal cancer resection. Dis Colon Rectum 47:279–286

    Article  PubMed  Google Scholar 

  19. Matthew FK, Luiz Felipe C, Luca S, Daniel PG, David D, Ian CL et al (2009) Predictive factors of pathologic complete response after neoadjuvant chemoradiation for rectal cancer. Ann Surg 250:582–589

    Google Scholar 

  20. Tulchinsky H, Shmueli E, Figer A, Klausner JM, Rabau M (2008) An interval >7 weeks between neoadjuvant therapy and surgery improves pathologic complete response and disease-free survival in patients with locally advanced rectal cancer. Ann Surg Oncol 15:2661–2667

    Article  PubMed  Google Scholar 

  21. Pucciarelli S, Toppan P, Friso ML, Russo V, Pasetto L, Urso E et al (2004) Complete pathologic response following preoperative chemoradiation therapy for middle to lower rectal cancer is not a prognostic factor for a better outcome. Dis Colon Rectum 47:1798–1807

    Article  PubMed  Google Scholar 

  22. Chan A, Wong A, Langevin J, Jenken D, Heine J, Buie D et al (2000) Preoperative chemotherapy and pelvic radiation for tethered or fixed rectal cancer: a phase II dose escalation study. Int J Radiat Oncol Biol Phys 48:843–856

    Article  CAS  PubMed  Google Scholar 

  23. Chang H, Jian J, Cheng S, Liu M, Leu S, Wang F et al (1998) Preoperative concurrent chemotherapy and radiotherapy in rectal cancer patients. J Formos Med Assoc 97:32–37

    CAS  Google Scholar 

  24. Chau I, Allen M, Cunningham D, Tait D, Brown G, Hill M et al (2003) Neoadjuvant systemic flurouracil and mitomycin C prior to synchronous chemoradiation is an effective strategy in locally advanced rectal cancer. Br J Cancer 88:1017–1024

    Article  CAS  PubMed  Google Scholar 

  25. Glynne-Jones R, Mawdsley S, Harrison M (2010) Cetuximab and chemoradiation for rectal cancer—is the water getting muddy? Acta Oncologica 49:278–286

    Article  CAS  PubMed  Google Scholar 

  26. Gerard JP, Azria D, Gourgou-Bourgade S, Martel-Laffay I, Hennequin C, Etienne P 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 Clin Oncol 28:1638–1644

    Article  CAS  PubMed  Google Scholar 

  27. Brown CL, Ternent CA, Thorson AG, Christensen MA, Blatchford GJ, Shashidharan M et al (2003) Response to preoperative chemoradiation in stage II and III rectal cancer. Dis Colon Rectum 46:1189–1193

    Article  PubMed  Google Scholar 

  28. Janjan NA, Khoo VS, Abbruzzese J, Pazdur R, Dubrow R, Cleary KR et al (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

    Article  CAS  PubMed  Google Scholar 

  29. Mohiuddin M, Regine WF, John WJ, Hagihara PF, McGrath PC, Kenady DE et al (2000) Preoperative chemoradiation in fixed distal rectal cancer: dose time factors for pathological complete response. Int J Radiat Oncol Biol Phys 46:883–888

    Article  CAS  PubMed  Google Scholar 

  30. Stipa F, Chessin DB, Shia J, Paty PB, Weiser M, Temple LKF et al (2006) A pathological complete response of rectal cancer to preoperative combined-modality therapy results in improved oncological outcome compared with those who achieve no downstaging on the basis of preoperative endorectal ultrasonography. Ann Surg Oncol 13:1047–1053

    Article  PubMed  Google Scholar 

  31. Theodoropoulos G, Wise WE, Padmanabhan A, Kerner BA, Taylor CW, Aguilar PS et al (2002) T-level downstaging and complete pathologic response after preoperative chemoradiation for advanced rectal cancer result in decreased recurrence and improved disease-free survival. Dis Colon Rectum 45:895–903

    Article  PubMed  Google Scholar 

  32. Garcia-Aguilar J, de Handa EH, Sirivongs P, Lee S, Madoff RD, Rothenberger DA (2003) A pathological complete response to preoperative chemoradiation is associated with lower local recurrence and improved survival in rectal cancer patients treated by mesorectal excision. Dis Colon Rectum 46:298–304

    Article  PubMed  Google Scholar 

  33. Onaitis MW, Noone RB, Fields R, Hurwitz H, Morse M, Jowell P et al (2001) Complete response to neoadjuvant chemoradiation for rectal cancer does not influence survival. Ann Surg Oncol 8:801–806

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We would like to thank Mrs. Rama Ranganathan and Mr. Sivakumar of the Department of Epidemiology and Tumor registry, Cancer Institute (WIA) for their invaluable help in analyzing the data and retrieving the patient records, respectively.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Surgical Oncology, Cancer Institute (WIA), Annexe Campus, No. 18, Sardar Patel road, Guindy, Chennai, 600036, India

    Sunil Bhanu Jayanand, Ramakrishnan Ayloor Seshadri & Ritesh Tapkire

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  1. Sunil Bhanu Jayanand
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  2. Ramakrishnan Ayloor Seshadri
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  3. Ritesh Tapkire
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Correspondence to Ramakrishnan Ayloor Seshadri.

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Jayanand, S.B., Seshadri, R.A. & Tapkire, R. Signet ring cell histology and non-circumferential tumors predict pathological complete response following neoadjuvant chemoradiation in rectal cancers. Int J Colorectal Dis 26, 23–27 (2011). https://doi.org/10.1007/s00384-010-1082-7

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  • DOI: https://doi.org/10.1007/s00384-010-1082-7

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