Epidermal growth factor receptor is a predictor of tumor response in locally advanced rectal cancer patients treated with preoperative radiotherapy

Giralt, Jordi; Eraso, Aranzazu; Armengol, Manel; Rosselló, J.; Majó, Joaquin; Ares, Carmen; Espín, Eloi; Benavente, Sergio; Torres, Inés de

doi:10.1016/s0360-3016(02)03752-5

Cited by 88 publications

(32 citation statements)

References 22 publications

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“…Patients with colorectal carcinomas showing EGFR staining by immunohistochemistry (IHC) in >50% of tumor cells have a poor prognosis [8]. High EGFR expression correlates with lower response rates in patients with advanced rectal cancer undergoing preoperative radiotherapy [31]. These findings suggest that EGFR overexpression is associated with advanced disease, increased metastatic ability and poor prognosis, although its impact on patient survival is less conclusive [10].…”

Section: Egfr and Colorectal Cancermentioning

confidence: 99%

KRAS mutation testing for predicting response to anti-EGFR therapy for colorectal carcinoma: proposal for an European quality assurance program

et al. 2008

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Novel therapeutic agents targeting the epidermal growth factor receptor (EGFR) have improved outcomes for patients with colorectal carcinoma. However, these therapies are effective only in a subset of patients. Activating mutations in the KRAS gene are found in 30-40% of colorectal tumors and are associated with poor response to anti-EGFR therapies. Thus, KRAS mutation status can predict which patient may or may not benefit from anti-EGFR therapy. Although many diagnostic tools have been developed for KRAS mutation analysis, validated methods and standardized testing procedures are lacking. This poses a challenge for the optimal use of anti-EGFR therapies in the management of colorectal carcinoma. Here we review the molecular basis of EGFR-targeted therapies and the resistance to treatment conferred by KRAS mutations. We also present guideline recommendations and a proposal for a European quality assurance program to help ensure accuracy and proficiency in KRAS mutation testing across the European Union.

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Section: Egfr and Colorectal Cancermentioning

confidence: 99%

KRAS mutation testing for predicting response to anti-EGFR therapy for colorectal carcinoma: proposal for an European quality assurance program

et al. 2008

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“…Some demonstrated that expression of the epidermal growth factor receptor (EGFR) predicts decreased pathologic response to preoperative radiotherapy or chemoradiation. [10][11][12] Overexpression of cyclooxygenase-2 has been associated with a poor response to preoperative chemoradiation. 13 Studies also have demonstrated that gene expression profiling may be used to predict response to preoperative chemoradiation.…”

Section: Discussionmentioning

confidence: 99%

Predictors of tumor response and downstaging in patients who receive preoperative chemoradiation for rectal cancer

Das

Skibber

Rodrı́guez-Bigas

et al. 2007

Cancer

299

208

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BACKGROUNDThe objective of this study was to identify predictive factors for pathologic complete response and tumor downstaging after preoperative chemoradiation for rectal cancer.METHODSBetween 1989 and 2004, 562 patients with nonmetastatic rectal adenocarcinoma received preoperative chemoradiation and underwent mesorectal excision. The median radiation dose was 45 Gray (Gy) (range, 19.8–58.6 Gy), 77% of patients received concurrent infusional 5‐fluorouracil, 20% of patients received concurrent capecitabine, and 3% of patients received other regimens.RESULTSNineteen percent of patients achieved a pathologic complete response (CR), whereas 20% of patients had only microscopic residual disease at surgery, and 61% of patients had macroscopic residual disease at surgery. Downstaging of the tumor stage occurred in 57% of patients. The results from a univariate analysis indicated that tumor circumferential extent >60% (P = .033) and pretreatment carcinoembryonic antigen (CEA) level >2.5 ng/mL (P = .015) were associated significantly with lower pathologic CR rates. The univariate analysis also indicated that tumor circumferential extent >60% (P = .001), pretreatment CEA level >2.5 ng/mL (P = .006), and distance from the anal verge >5 cm (P = .035) were associated significantly with lower downstaging rates. The results from a multivariate logistic regression analysis indicated that greater circumferential extent of tumor (odds ratio [OR], 0.43; P = .033) independently predicted a lower pathologic CR rate. The multivariate logistic regression analysis also indicated that greater circumferential extent of tumor (OR, 0.49; P = .020) and greater distance from the anal verge (OR, 0.46; P = .010) independently predicted a lower downstaging rate.CONCLUSIONSCircumferential extent of tumor, CEA level, and distance from the anal verge predicted for the pathologic response to preoperative chemoradiation for patients with rectal cancer. Therefore, these factors may be used to predict outcomes for patients, to develop risk‐adapted treatment strategies, and to target patients who participate in trials of newer therapies. Cancer 2007. © 2007 American Cancer Society.

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“…Because it is known that both EGFR and Ras are strong modulators of radioresistance (4,5,19,20), these results are of special importance for the design of targeting strategies to interfere with EGFR signaling in the context of resistance of EGFR-overexpressing or EGFR-mutated human solid tumors to radiotherapy. EGFR-dependent PI3K-AKT From same samples used for Ras-GTP assay, 100-Ag protein was subjected to SDS-PAGE and the level of p-AKT (Ser 472/473 ) was analyzed with specific antibody.…”

Section: Discussionmentioning

confidence: 99%

“…This mechanism may also play a role in radioresistance of RAS-mutated tumors. Moreover, experimental and clinical evidence exists that overexpression or mutation of EGFR mediates tumor resistance to both chemotherapy and especially radiotherapy (18)(19)(20)(21)(22)(23), and EGFR overexpression has been correlated with accelerated repopulation of tumors undergoing radiotherapy (24).…”

Section: Introductionmentioning

confidence: 99%

Stimulated PI3K-AKT Signaling Mediated through Ligand or Radiation-Induced EGFR Depends Indirectly, but not Directly, on Constitutive K-Ras Activity

Toulany

Baumann

Rodemann

2007

Molecular Cancer Research

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Epidermal growth factor receptor is a predictor of tumor response in locally advanced rectal cancer patients treated with preoperative radiotherapy

Cited by 88 publications

References 22 publications

KRAS mutation testing for predicting response to anti-EGFR therapy for colorectal carcinoma: proposal for an European quality assurance program

KRAS mutation testing for predicting response to anti-EGFR therapy for colorectal carcinoma: proposal for an European quality assurance program

Predictors of tumor response and downstaging in patients who receive preoperative chemoradiation for rectal cancer

Stimulated PI3K-AKT Signaling Mediated through Ligand or Radiation-Induced EGFR Depends Indirectly, but not Directly, on Constitutive K-Ras Activity

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