Skip to main content
Log in

Gender-Related Differences in Repopulation and Early Tumor Response to Preoperative Radiotherapy in Rectal Cancer Patients

  • Original Article
  • Published:
Journal of Gastrointestinal Surgery Aims and scope

Abstract

Purpose

Inhibition of tumor proliferation rate based on bromodeoxyuridine labelling index (BrdUrdLI), S-phase fraction (SPF) and MIB-1 labelling index (MIB-1 LI) as an early rectal cancer response to preoperative radiotherapy (RT).

Methods and materials

A total of 122 patients qualified either for short RT (5 Gy/fraction/5 days) and surgery about 1 week after RT (schedule I) or for short RT and a 4-week interval before surgery (schedule II). Tumor samples were taken twice from each patient: before RT and at the time of surgery. In each sample, the BrdUrdLI, SPF and MIB-1 were calculated. Early tumor response was assessed by a biologist, a pathologist and surgeons.

Results

Fifty-six patients were treated according to schedule I and 66 patients according to schedule II. Mean BrdUrdLI, SPF and MIB-1 LI before RT were 8.8%, 21.0% and 53.3%, respectively, and these values did not differ between the two compared groups. After RT, tumors showed statistically significant growth inhibition based on all assessed biological markers. As pretreatment assessed parameter was not predictive for early clinical and pathologic tumor response, prognostic role of the relative value (RV), that is, the ratio of assessed parameter after RT to before RT for each of the assessed markers, was considered. The ratios were calculated separately for fast and slowly proliferating tumors and separately for male and female patients. Fast proliferating tumors were more responsive. Differences with regard to sex were visible only in slowly proliferating tumors. Accelerated cell repopulation (4.8–28%/day) was noticed in female slowly proliferating tumors about 4 weeks after RT. Only for relative MIB-1 LI it was possible to show significant correlation with pathological tumor regression. Lack of such correlation for BrdUrdLI and SPF might reflect accelerated repopulation, particularly in slowly proliferating female tumors.

Conclusions

Accelerated repopulation was noticed in slowly proliferating tumors in females about 4 weeks after RT.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Folkesson J, Birgisson H, Pahlmann L et al. Swedish rectal cancer trial: long lasting benefits from radiotherapy on survival and local recurrence rate. J Clin Oncol 2005;23:5644–5650.

    Article  PubMed  Google Scholar 

  2. Pettersson D, Cedermark B, Holm T et al. Interim analysis of the Stockholm III trial of preoperative radiotherapy regimens for rectal cancer. Br J Surg. 2010;97:580–587.

    Article  PubMed  CAS  Google Scholar 

  3. Gasinska A, Skolyszewski J, Popiela T et al. Bromodeoxyuridine labelling index as an indicator of early tumor response to preoperative radiotherapy in patients with rectal cancer. J Gastrointest Surg. 2007;11:520–528.

    Article  PubMed  Google Scholar 

  4. Wichmann MW, Muller C, Homung HM et al. Gender differences in long-term survival of patients with colorectal cancer. Br J Surg. 2001;88:1092–1098.

    Article  PubMed  CAS  Google Scholar 

  5. Koo JH, Jalaludin B, Wong et al. Improved survival in young women with colorectal cancer. Am J Gastroenterol. 2008;103:1488–1495.

    Article  PubMed  Google Scholar 

  6. Hendifar A, Yang D, Lenz F et al. Gender disparities in metastatic colorectal cancer survival. Clin Cancer Res. 2009;15:6391–6397.

    Article  PubMed  Google Scholar 

  7. World Health Organization. International histological classification of tumours. Histological typing of intestinal tumours. Jass JR, Sobin LH, editors. Berlin: Springer, 1989.

  8. Gasińska A, Urbanski K, Jakubowicz J et al. Tumour cell kinetics as a prognostic factor in squamous cell carcinoma of the cervix treated with radiotherapy. Radiother Oncol 1999;50:77–84.

    Article  PubMed  Google Scholar 

  9. Therasse P, Arbuck SG, Eisenhauer EA et al. New guidelines to evaluate the response to treatment in solid tumours. J Nat Cancer Inst. 2000;92:205–216.

    Article  PubMed  CAS  Google Scholar 

  10. Dworak O, Keilholz L, Hoffmann A. Pathological features of rectal cancer after preoperative radiochemotherapy. Int J Colorect Dis. 1997;12:19–23.

    Article  CAS  Google Scholar 

  11. American Joint Commission on Cancer. AJCC cancer staging manual, 5th edn. Philadelphia: Lippincott-Raven Publishers, 1997.

    Google Scholar 

  12. Bergstrom Ch, Palmqvist R, Denekamp J et al. Factors influencing the estimates of proliferative labelling indices in rectal cancer. Radiother Oncol. 1998;46:169–177.

    Article  PubMed  CAS  Google Scholar 

  13. Fluge O, Gravdal K, Carlsen E et al. Expression of EZH2 and Ki-67 in colorectal cancer and associations with treatment response and prognosis. Br J Cancer. 2009;101:1282–1289.

    Article  PubMed  CAS  Google Scholar 

  14. Terry NHA, Meistrich ML, Roubein LD et al. Cellular kinetics in rectal cancer. Br J Cancer. 1995;72:435–441.

    Article  PubMed  CAS  Google Scholar 

  15. Willett ChG, Warland G, Coen J et al. Rectal cancer: the influence of tumour proliferation on response to preoperative irradiation. Int J Radiat Oncol Biol Phys. 1995;32:57–61.

    Article  PubMed  CAS  Google Scholar 

  16. Wilson GD. A new look at proliferation. Acta Oncol. 2001;40:989–994.

    Article  PubMed  CAS  Google Scholar 

  17. Withers HR, Taylor JMG, Maciejewski B. The hazard of accelerated tumor repopulation during radiotherapy. Acta Oncol. 1988;27:131–145.

    Article  PubMed  CAS  Google Scholar 

  18. Suwinski R, Taylor JMG, Withers HR. Rapid growth of microscopic rectal cancer as a determinant of response to preoperative radiation therapy. Int J Radiat Oncol Biol Phys. 1998;42:943–951.

    Article  PubMed  CAS  Google Scholar 

  19. Withers HR. Treatment-induced accelerated human tumor growth. Sem Radiat Oncol. 1993;3:135–143.

    Article  Google Scholar 

  20. Trott KR. Perspectives of experimental research on repopulation during radiotherapy. Int J Radiat Biol. 2003;79:577–580.

    Article  PubMed  CAS  Google Scholar 

  21. Tarnawski R, Fowler J, Skladowski K et al. How fast is repopulation of tumor cells during the treatment gap? Int J Radiat Oncol Biol Phys. 2002;54:229–236.

    PubMed  Google Scholar 

  22. Courdi A, Tubiana M, Chavaudra N et al. Changes in labeling indices of human tumors after irradiation. Int J Radiat Oncol Biol Phys. 1980;6:1639–1644.

    Article  PubMed  CAS  Google Scholar 

  23. Silvestrini R, Daidone MG, Valagussa P et al. Cell kinetics as a prognostic marker in locally advanced breast cancer. Cancer Treat Rep. 1987;71:375–379.

    PubMed  CAS  Google Scholar 

  24. Bentzen SM, Atosoy BM, Daley FM et al. Epidermal growth factor receptor expression in pretreatment biopsies from head and neck squamous cell carcinoma as a predictive factor for a benefit from accelerated radiation therapy in a randomized controlled trial. J Clin Oncol. 2005;23:5560–5567.

    Article  PubMed  CAS  Google Scholar 

  25. Thames HD, Peters LJ, Withers HR et al. Accelerated fractionation vs hyperfractionation: Rationales for several treatments per day. Int J Radiat Oncol Biol Phys. 1983;9:127–138.

    PubMed  Google Scholar 

  26. Peters LJ, Ang KK, Thames HD. Accelerated fractionation in radiation treatment of head and neck cancer: a critical comparison of different strategies. Acta Oncol. 1988;27:185–191.

    Article  PubMed  CAS  Google Scholar 

  27. Fowler JF. Potential for increasing the differential response between tumors and normal tissues: can proliferation rate be used? Int J Radiat Oncol Biol Phys. 1986;12:641–645.

    Article  PubMed  CAS  Google Scholar 

  28. Press OA, Zhang W, Gordon MA et al. Gender-related survival differences associated with EGFR polymorphisms in metastatic colon cancer. Cancer Res. 2008;68,8:3037–3042.

    Article  PubMed  CAS  Google Scholar 

  29. Zhang W, Press OA, Haiman ChA et al. Association on methylenetetrahydrofolate reductase gene polymorphisms and sex-specific survival in patients with metastatic colon cancer. J Clin Oncol. 2007;24:3726–3731.

    Article  Google Scholar 

Download references

Acknowledgements

The authors thank Anna Cichocka for valuable assistance. This work was supported by a grant from the State Committee for Scientific Research No. PBZ-KBN-091/P05/2003.

Conflict of interest

None.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Anna Gasinska.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gasinska, A., Richter, P., Darasz, Z. et al. Gender-Related Differences in Repopulation and Early Tumor Response to Preoperative Radiotherapy in Rectal Cancer Patients. J Gastrointest Surg 15, 1568–1576 (2011). https://doi.org/10.1007/s11605-011-1589-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11605-011-1589-4

Keywords

Navigation