Top

Published in:

01-04-2012 | Colorectal Cancer

Radiation-Induced Apoptosis of Peripheral Blood Lymphocytes is Correlated with Histological Regression of Rectal Cancer in Response to Preoperative Chemoradiotherapy

Authors: Soichiro Ishihara, MD, PhD, Hisae Iinuma, PhD, Yoshihisa Fukushima, MD, Takuya Akahane, MD, Atsushi Horiuchi, MD, Ryu Shimada, MD, Hajime Shibuya, MD, PhD, Tamuro Hayama, MD, PhD, Hideki Yamada, MD, PhD, Keijiro Nozawa, MD, PhD, Keiji Matsuda, MD, PhD, Toshiaki Watanabe, MD, PhD

Published in: Annals of Surgical Oncology | Issue 4/2012

Abstract

Purpose

The response of rectal cancer to preoperative chemoradiotherapy (PRT) varies widely among patients, and predictors of the response remain to be elucidated. The purpose of this study is to investigate whether radiation-induced apoptosis (RIA) of peripheral blood lymphocytes (PBLs) reflects the underlying intrinsic radiosensitivity of rectal cancer.

Methods

Forty-one patients with clinical T3-4, M0 low rectal cancers, treated with PRT and curative surgery, were retrospectively studied. PBLs were obtained from blood samples of the patients, irradiated at 0, 2, 8, and 16 Gy in vitro, and analyzed for RIA by flow cytometry using Annexin V (AV) and propidium iodide (PI). The correlation of the RIA of PBLs and histological regression of rectal cancer in response to PRT was examined.

Results

Both the proportions of AV+/PI− PBLs (early apoptosis) and AV+/PI + PBLs (late apoptosis) were significantly higher in patients with high histological regression than in those with low histological regression. Age, sex, tumor size, and clinical T and N stages did not affect the RIA of PBLs.

Conclusions

This study showed that the RIA of PBLs is correlated with the histological regression of rectal cancer in response to PRT and suggested that the radiosensitivity of rectal cancer might be estimated by the RIA of PBLs.

Folkesson J, Birgisson H, Pahlman L, Cedermark B, Glimelius B, Gunnarsson U. Swedish Rectal Cancer Trial: long-lasting benefits from radiotherapy on survival and local recurrence rate. J Clin Oncol. 2005;23(24):5644–50.PubMedCrossRef

Peeters KC, Marijnen CA, Nagtegaal ID, et al. The TME trial after a median follow-up of 6 years: increased local control but no survival benefit in irradiated patients with resectable rectal carcinoma. Ann Surg. 2007;246(5):693–701.PubMedCrossRef

Sauer R, Becker H, Hohenberger W, et al. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med. 2004;351(17):1731–40.PubMedCrossRef

Ishihara S, Watanabe T, Akahane T, et al. Prognostic significance of adverse events associated with preoperative radiotherapy for rectal cancer. Int J Colorectal Dis. 2011;26(7):911–7.PubMedCrossRef

Gabelova A, Farkasova T, Gurska S, Machackova Z, Lukacko P, Witkovsky V. Radiosensitivity of peripheral blood lymphocytes from healthy donors and cervical cancer patients; the correspondence of in vitro data with the clinical outcome. Neoplasma. 2008;55(3):182–91.PubMed

Bordon E, Henriquez Hernandez LA, Lara PC, et al 2009 Prediction of clinical toxicity in localized cervical carcinoma by radio-induced apoptosis study in peripheral blood lymphocytes (PBLs). Radiat Oncol. 4:58.PubMedCrossRef

Borgmann K, Hoeller U, Nowack S, et al. Individual radiosensitivity measured with lymphocytes may predict the risk of acute reaction after radiotherapy. Int J Radiat Oncol Biol Phys. 2008;71(1):256–64.PubMedCrossRef

Schnarr K, Boreham D, Sathya J, Julian J, Dayes IS. Radiation-induced lymphocyte apoptosis to predict radiation therapy late toxicity in prostate cancer patients. Int J Radiat Oncol Biol Phys. 2009;74(5):1424–30.PubMedCrossRef

Ishihara S, Watanabe T, Kiyomatsu T, Yasuda K, Nagawa H. Prognostic significance of response to preoperative radiotherapy, lymph node metastasis, and CEA level in patients undergoing total mesorectal excision of rectal cancer. Int J Colorectal Dis. 2010;25(12):1417–25.PubMedCrossRef

10.

Fu CG, Tominaga O, Nagawa H, et al. Role of p53 and p21/WAF1 detection in patient selection for preoperative radiotherapy in rectal cancer patients. Dis Colon Rectum. 1998;41(1):68–74.PubMedCrossRef

11.

Das P, Skibber JM, Rodriguez-Bigas MA, et al. Predictors of tumor response and downstaging in patients who receive preoperative chemoradiation for rectal cancer. Cancer. 2007;109(9):1750–5.PubMedCrossRef

12.

Yoon SM, Kim DY, Kim TH, et al. Clinical parameters predicting pathologic tumor response after preoperative chemoradiotherapy for rectal cancer. Int J Radiat Oncol Biol Phys. 2007;69(4):1167–72.PubMedCrossRef

13.

Chang HJ, Jung KH, Kim DY, et al. Bax, a predictive marker for therapeutic response to preoperative chemoradiotherapy in patients with rectal carcinoma. Hum Pathol. 2005;36(4):364–71.PubMedCrossRef

14.

Kobayashi H, Hashiguchi Y, Ueno H, Shinto E, Kajiwara Y, Mochizuki H. Absence of cyclooxygenase-2 protein expression is a predictor of tumor regression in rectal cancer treated with preoperative short-term chemoradiotherapy. Dis Colon Rectum. 2007;50(9):1354–62.PubMedCrossRef

15.

Kim NK, Park JK, Lee KY, et al. p53, BCL-2, and Ki-67 expression according to tumor response after concurrent chemoradiotherapy for advanced rectal cancer. Ann Surg Oncol. 2001;8(5):418–24.PubMedCrossRef

16.

Terzi C, Canda AE, Sagol O, et al. Survivin, p53, and Ki-67 as predictors of histopathologic response in locally advanced rectal cancer treated with preoperative chemoradiotherapy. Int J Colorectal Dis. 2008;23(1):37–45.PubMedCrossRef

17.

Watanabe T, Komuro Y, Kiyomatsu T, et al. Prediction of sensitivity of rectal cancer cells in response to preoperative radiotherapy by DNA microarray analysis of gene expression profiles. Cancer Res. 2006;66(7):3370–4.PubMedCrossRef

18.

Ghadimi BM, Grade M, Difilippantonio MJ, et al. Effectiveness of gene expression profiling for response prediction of rectal adenocarcinomas to preoperative chemoradiotherapy. J Clin Oncol. 2005;23(9):1826–38.PubMedCrossRef

19.

Liersch T, Grade M, Gaedcke J, et al. Preoperative chemoradiotherapy in locally advanced rectal cancer: correlation of a gene expression-based response signature with recurrence. Cancer Genet Cytogenet. 2009;190(2):57–65.PubMedCrossRef

20.

Kitayama J, Yasuda K, Kawai K, Sunami E, Nagawa H. Circulating lymphocyte number has a positive association with tumor response in neoadjuvant chemoradiotherapy for advanced rectal cancer. Radiat Oncol. 2010;5:47.PubMedCrossRef

21.

Lim SB, Choi HS, Jeong SY, et al. Optimal surgery time after preoperative chemoradiotherapy for locally advanced rectal cancers. Ann Surg. 2008;248(2):243–51.PubMedCrossRef

22.

Dolinsky CM, Mahmoud NN, Mick R, et al. Effect of time interval between surgery and preoperative chemoradiotherapy with 5-fluorouracil or 5-fluorouracil and oxaliplatin on outcomes in rectal cancer. J Surg Oncol. 2007;96(3):207–12.PubMedCrossRef

23.

Suarez J, Vera R, Balen E, et al. Pathologic response assessed by Mandard grade is a better prognostic factor than down staging for disease-free survival after preoperative radiochemotherapy for advanced rectal cancer. Colorectal Dis. 2008;10(6):563–8.PubMedCrossRef

24.

Beddy D, Hyland JM, Winter DC, et al. A simplified tumor regression grade correlates with survival in locally advanced rectal carcinoma treated with neoadjuvant chemoradiotherapy. Ann Surg Oncol. 2008 15(12):3471.PubMedCrossRef

25.

Topova L, Hellmich G, Puffer E, et al. Prognostic value of tumor response to neoadjuvant therapy in rectal carcinoma. Dis Colon Rectum. 2011;54(4):401–11.PubMedCrossRef

26.

Tsujinaka S, Kawamura YJ, Konishi F, Aihara H, Maeda T, Mizokami K. Long-term efficacy of preoperative radiotherapy for locally advanced low rectal cancer. Int J Colorectal Dis. 2008;23(1):67–76.PubMedCrossRef

27.

Pucciarelli S, Toppan P, Friso ML, et al. 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. 2004;47(11):1798–807.PubMedCrossRef

28.

Saigusa S, Tanaka K, Toiyama Y, et al. Correlation of CD133, OCT4, and SOX2 in rectal cancer and their association with distant recurrence after chemoradiotherapy. Ann Surg Oncol. 2009;16(12):3488–98.PubMedCrossRef

Title: Radiation-Induced Apoptosis of Peripheral Blood Lymphocytes is Correlated with Histological Regression of Rectal Cancer in Response to Preoperative Chemoradiotherapy
Authors: Soichiro Ishihara, MD, PhD
Hisae Iinuma, PhD
Yoshihisa Fukushima, MD
Takuya Akahane, MD
Atsushi Horiuchi, MD
Ryu Shimada, MD
Hajime Shibuya, MD, PhD
Tamuro Hayama, MD, PhD
Hideki Yamada, MD, PhD
Keijiro Nozawa, MD, PhD
Keiji Matsuda, MD, PhD
Toshiaki Watanabe, MD, PhD
Publication date: 01-04-2012
Publisher: Springer-Verlag
Published in: Annals of Surgical Oncology / Issue 4/2012
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI: https://doi.org/10.1245/s10434-011-2057-9

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Radiation-Induced Apoptosis of Peripheral Blood Lymphocytes is Correlated with Histological Regression of Rectal Cancer in Response to Preoperative Chemoradiotherapy

Abstract

Purpose

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 4/2012

Impact of FOXA1 Expression on the Prognosis of Patients with Hormone Receptor-Positive Breast Cancer

Preoperative Ultrasound is Not Useful for Identifying Nodal Metastasis in Melanoma Patients Undergoing Sentinel Node Biopsy: Preoperative Ultrasound in Clinically Node-Negative Melanoma

Which Eligible Breast Conservation Patients Choose Mastectomy in the Setting of Newly Diagnosed Breast Cancer?

Significance of Metastatic Lymph Node Ratio on Stimulated Thyroglobulin Levels in Papillary Thyroid Carcinoma after Prophylactic Unilateral Central Neck Dissection

Predictors of Nipple–Areolar Complex Involvement by Breast Carcinoma: Histopathologic Analysis of 787 Consecutive Therapeutic Mastectomy Specimens

High Lymph Node Yield is Related to Microsatellite Instability in Colon Cancer