Molecular markers predict distant metastases after adjuvant chemoradiation for rectal cancer

Jun Won Kim, Yong Bae Kim, Jun Jeong Choi, Woong Sub Koom, Hoguen Kim, Nam Kyu Kim, Joong Bae Ahn, Ikjae Lee, Jae Ho Cho, Ki Chang Keum

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Purpose: The outcomes of adjuvant chemoradiation for locally advanced rectal cancer are nonuniform among patients with matching prognostic factors. We explored the role of molecular markers for predicting the outcome of adjuvant chemoradiation for rectal cancer patients. Methods and Materials: The study included 68 patients with stages II to III rectal adenocarcinoma who were treated with total mesorectal excision and adjuvant chemoradiation. Chemotherapy based on 5-fluorouracil and leucovorin was intravenously administered each month for 6-12 cycles. Radiation therapy consisted of 54 Gy delivered in 30 fractions. Immunostaining of surgical specimens for COX-2, EGFR, VEGF, thymidine synthase (TS), and Raf kinase inhibitor protein (RKIP) was performed. Results: The median follow-up was 65 months. Eight locoregional (11.8%) and 13 distant (19.1%) recurrences occurred. Five-year locoregional failure-free survival (LRFFS), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) rates for all patients were 83.9%, 78.7%, 66.7%, and 73.8%, respectively. LRFFS was not correlated with TNM stage, surgical margin, or any of the molecular markers. VEGF overexpression was significantly correlated with decreased DMFS (P=.045), while RKIP-positive results were correlated with increased DMFS (P=.025). In multivariate analyses, positive findings for COX-2 (COX-2+) and VEGF (VEGF+) and negative findings for RKIP (RKIP-) were independent prognostic factors for DMFS, DFS, and OS (P=.035,.014, and.007 for DMFS;.021,.010, and <.0001 for DFS; and.004,.012, and.001 for OS). The combination of both COX-2+ and VEGF+ (COX-2+/VEGF+) showed a strong correlation with decreased DFS (P=.007), and the combinations of RKIP+/COX-2- and RKIP+/VEGF- showed strong correlations with improved DFS compared with the rest of the patients (P=.001 and <.0001, respectively). Conclusions: Molecular markers can be valuable in predicting treatment outcome of adjuvant chemoradiation for rectal cancer patients.

Original languageEnglish
Pages (from-to)e577-e584
JournalInternational Journal of Radiation Oncology Biology Physics
Volume84
Issue number5
DOIs
Publication statusPublished - 2012 Dec 1

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Phosphatidylethanolamine Binding Protein
metastasis
Rectal Neoplasms
markers
Vascular Endothelial Growth Factor A
cancer
Neoplasm Metastasis
Disease-Free Survival
Survival
inhibitors
proteins
Leucovorin
Thymidine Kinase
Fluorouracil
Adenocarcinoma
Radiotherapy
Multivariate Analysis
Survival Rate
Recurrence
Drug Therapy

All Science Journal Classification (ASJC) codes

  • Radiation
  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

Cite this

@article{0c81dd9b2f7b4d80a747796e3da54ca6,
title = "Molecular markers predict distant metastases after adjuvant chemoradiation for rectal cancer",
abstract = "Purpose: The outcomes of adjuvant chemoradiation for locally advanced rectal cancer are nonuniform among patients with matching prognostic factors. We explored the role of molecular markers for predicting the outcome of adjuvant chemoradiation for rectal cancer patients. Methods and Materials: The study included 68 patients with stages II to III rectal adenocarcinoma who were treated with total mesorectal excision and adjuvant chemoradiation. Chemotherapy based on 5-fluorouracil and leucovorin was intravenously administered each month for 6-12 cycles. Radiation therapy consisted of 54 Gy delivered in 30 fractions. Immunostaining of surgical specimens for COX-2, EGFR, VEGF, thymidine synthase (TS), and Raf kinase inhibitor protein (RKIP) was performed. Results: The median follow-up was 65 months. Eight locoregional (11.8{\%}) and 13 distant (19.1{\%}) recurrences occurred. Five-year locoregional failure-free survival (LRFFS), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) rates for all patients were 83.9{\%}, 78.7{\%}, 66.7{\%}, and 73.8{\%}, respectively. LRFFS was not correlated with TNM stage, surgical margin, or any of the molecular markers. VEGF overexpression was significantly correlated with decreased DMFS (P=.045), while RKIP-positive results were correlated with increased DMFS (P=.025). In multivariate analyses, positive findings for COX-2 (COX-2+) and VEGF (VEGF+) and negative findings for RKIP (RKIP-) were independent prognostic factors for DMFS, DFS, and OS (P=.035,.014, and.007 for DMFS;.021,.010, and <.0001 for DFS; and.004,.012, and.001 for OS). The combination of both COX-2+ and VEGF+ (COX-2+/VEGF+) showed a strong correlation with decreased DFS (P=.007), and the combinations of RKIP+/COX-2- and RKIP+/VEGF- showed strong correlations with improved DFS compared with the rest of the patients (P=.001 and <.0001, respectively). Conclusions: Molecular markers can be valuable in predicting treatment outcome of adjuvant chemoradiation for rectal cancer patients.",
author = "Kim, {Jun Won} and Kim, {Yong Bae} and Choi, {Jun Jeong} and Koom, {Woong Sub} and Hoguen Kim and Kim, {Nam Kyu} and Ahn, {Joong Bae} and Ikjae Lee and Cho, {Jae Ho} and Keum, {Ki Chang}",
year = "2012",
month = "12",
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doi = "10.1016/j.ijrobp.2012.07.2371",
language = "English",
volume = "84",
pages = "e577--e584",
journal = "International Journal of Radiation Oncology Biology Physics",
issn = "0360-3016",
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}

Molecular markers predict distant metastases after adjuvant chemoradiation for rectal cancer. / Kim, Jun Won; Kim, Yong Bae; Choi, Jun Jeong; Koom, Woong Sub; Kim, Hoguen; Kim, Nam Kyu; Ahn, Joong Bae; Lee, Ikjae; Cho, Jae Ho; Keum, Ki Chang.

In: International Journal of Radiation Oncology Biology Physics, Vol. 84, No. 5, 01.12.2012, p. e577-e584.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Molecular markers predict distant metastases after adjuvant chemoradiation for rectal cancer

AU - Kim, Jun Won

AU - Kim, Yong Bae

AU - Choi, Jun Jeong

AU - Koom, Woong Sub

AU - Kim, Hoguen

AU - Kim, Nam Kyu

AU - Ahn, Joong Bae

AU - Lee, Ikjae

AU - Cho, Jae Ho

AU - Keum, Ki Chang

PY - 2012/12/1

Y1 - 2012/12/1

N2 - Purpose: The outcomes of adjuvant chemoradiation for locally advanced rectal cancer are nonuniform among patients with matching prognostic factors. We explored the role of molecular markers for predicting the outcome of adjuvant chemoradiation for rectal cancer patients. Methods and Materials: The study included 68 patients with stages II to III rectal adenocarcinoma who were treated with total mesorectal excision and adjuvant chemoradiation. Chemotherapy based on 5-fluorouracil and leucovorin was intravenously administered each month for 6-12 cycles. Radiation therapy consisted of 54 Gy delivered in 30 fractions. Immunostaining of surgical specimens for COX-2, EGFR, VEGF, thymidine synthase (TS), and Raf kinase inhibitor protein (RKIP) was performed. Results: The median follow-up was 65 months. Eight locoregional (11.8%) and 13 distant (19.1%) recurrences occurred. Five-year locoregional failure-free survival (LRFFS), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) rates for all patients were 83.9%, 78.7%, 66.7%, and 73.8%, respectively. LRFFS was not correlated with TNM stage, surgical margin, or any of the molecular markers. VEGF overexpression was significantly correlated with decreased DMFS (P=.045), while RKIP-positive results were correlated with increased DMFS (P=.025). In multivariate analyses, positive findings for COX-2 (COX-2+) and VEGF (VEGF+) and negative findings for RKIP (RKIP-) were independent prognostic factors for DMFS, DFS, and OS (P=.035,.014, and.007 for DMFS;.021,.010, and <.0001 for DFS; and.004,.012, and.001 for OS). The combination of both COX-2+ and VEGF+ (COX-2+/VEGF+) showed a strong correlation with decreased DFS (P=.007), and the combinations of RKIP+/COX-2- and RKIP+/VEGF- showed strong correlations with improved DFS compared with the rest of the patients (P=.001 and <.0001, respectively). Conclusions: Molecular markers can be valuable in predicting treatment outcome of adjuvant chemoradiation for rectal cancer patients.

AB - Purpose: The outcomes of adjuvant chemoradiation for locally advanced rectal cancer are nonuniform among patients with matching prognostic factors. We explored the role of molecular markers for predicting the outcome of adjuvant chemoradiation for rectal cancer patients. Methods and Materials: The study included 68 patients with stages II to III rectal adenocarcinoma who were treated with total mesorectal excision and adjuvant chemoradiation. Chemotherapy based on 5-fluorouracil and leucovorin was intravenously administered each month for 6-12 cycles. Radiation therapy consisted of 54 Gy delivered in 30 fractions. Immunostaining of surgical specimens for COX-2, EGFR, VEGF, thymidine synthase (TS), and Raf kinase inhibitor protein (RKIP) was performed. Results: The median follow-up was 65 months. Eight locoregional (11.8%) and 13 distant (19.1%) recurrences occurred. Five-year locoregional failure-free survival (LRFFS), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) rates for all patients were 83.9%, 78.7%, 66.7%, and 73.8%, respectively. LRFFS was not correlated with TNM stage, surgical margin, or any of the molecular markers. VEGF overexpression was significantly correlated with decreased DMFS (P=.045), while RKIP-positive results were correlated with increased DMFS (P=.025). In multivariate analyses, positive findings for COX-2 (COX-2+) and VEGF (VEGF+) and negative findings for RKIP (RKIP-) were independent prognostic factors for DMFS, DFS, and OS (P=.035,.014, and.007 for DMFS;.021,.010, and <.0001 for DFS; and.004,.012, and.001 for OS). The combination of both COX-2+ and VEGF+ (COX-2+/VEGF+) showed a strong correlation with decreased DFS (P=.007), and the combinations of RKIP+/COX-2- and RKIP+/VEGF- showed strong correlations with improved DFS compared with the rest of the patients (P=.001 and <.0001, respectively). Conclusions: Molecular markers can be valuable in predicting treatment outcome of adjuvant chemoradiation for rectal cancer patients.

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U2 - 10.1016/j.ijrobp.2012.07.2371

DO - 10.1016/j.ijrobp.2012.07.2371

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JO - International Journal of Radiation Oncology Biology Physics

JF - International Journal of Radiation Oncology Biology Physics

SN - 0360-3016

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