Yonsei Med J.  2015 Nov;56(6):1461-1477. 10.3349/ymj.2015.56.6.1461.

New Perspectives on Predictive Biomarkers of Tumor Response and Their Clinical Application in Preoperative Chemoradiation Therapy for Rectal Cancer

• Kim NK
• Hur H

• KMID: 2345872
• DOI: http://doi.org/10.3349/ymj.2015.56.6.1461

Abstract

Preoperative chemoradiation therapy (CRT) is the standard treatment for patients with locally advanced rectal cancer (LARC) and can improve local control and survival outcomes. However, the responses of individual tumors to CRT are not uniform and vary widely, from complete response to disease progression. Patients with resistant tumors can be exposed to irradiation and chemotherapy that are both expensive and at times toxic without benefit. In contrast, about 60% of tumors show tumor regression and T and N down-staging. Furthermore, a pathologic complete response (pCR), which is characterized by sterilization of all tumor cells, leads to an excellent prognosis and is observed in approximately 10-30% of cases. This variety in tumor response has lead to an increased need to develop a model predictive of responses to CRT in order to identify patients who will benefit from this multimodal treatment. Endoscopy, magnetic resonance imaging, positron emission tomography, serum carcinoembryonic antigen, and molecular biomarkers analyzed using immunohistochemistry and gene expression profiling are the most commonly used predictive models in preoperative CRT. Such modalities guide clinicians in choosing the best possible treatment options and the extent of surgery for each individual patient. However, there are still controversies regarding study outcomes, and a nomogram of combined models of future trends is needed to better predict patient response. The aim of this article was to review currently available tools for predicting tumor response after preoperative CRT in rectal cancer and to explore their applicability in clinical practice for tailored treatment.

Keyword

Rectal neoplasms; chemoradiotherapy; biological markers

MeSH Terms

Biomarkers, Tumor/blood
Carcinoembryonic Antigen/blood
*Chemoradiotherapy
Combined Modality Therapy
Female
Gene Expression Profiling
Humans
Immunohistochemistry/methods
Middle Aged
Neoadjuvant Therapy
Positron-Emission Tomography/methods
Predictive Value of Tests
Preoperative Care/*methods
Prognosis
Rectal Neoplasms/*drug therapy/*radiotherapy/surgery
Remission Induction
Biomarkers, Tumor
Carcinoembryonic Antigen

Figure

• 

  Fig. 1 Primary tumor response after preoperative chemoradiation therapy for rectal cancer. (A) Complete pathologic response. (B) Poor response. The arrow indicates the residual tumor.

• 

  Fig. 2 Systemic progression of disease during preoperative chemoradiation therapy. The arrow indicates the liver metastasis (A) and the paraaortic lymph node metastasis (B).

• 

  Fig. 3 Various endoscopic findings of primary tumors after preoperative chemoradiation therapy. (A) Whitening of the mucosa. (B) Association of telangiectasia. (C) Deep ulceration. (D) Palpable nodule.

• 

  Fig. 4 Various findings according to MRI after preoperative chemoradiation therapy for rectal cancer. Good response: (A) MRI before preoperative CRT; (B) MRI after preoperative CRT. Poor response: (C) MRI before preoperative CRT; (D) MRI after preoperative CRT. CRT, chemoradiation therapy.

• 

  Fig. 5 Perfusion MRI imaging. (A) Good response. (B) Poor response.

• 

  Fig. 6 18F-FDG PET before and after preoperative chemoradiation therapy for rectal cancer. (A) Before and (B) after in a pathologic complete response case. (C) Before and (D) after in a poor response case. 18F-FDG PET, fluorine-18-fluorodeoxyglucose/positron emission tomography.

• 

  Fig. 7 Direct invasion of seminal vesicles and prostate gland with a positive circumferential resection margin after preoperative CRT. The arrow indicates tumor before preoperative CRT (A) and after preoperative CRT (B). CRT, chemoradiation therapy.

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