Predicting pathological complete response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer: a systematic review

Ryan, J.; Warrier, Satish; Lynch, A. C.; Ramsay, Robert G.; Phillips, Wayne A.; Heriot, Alexander G.

doi:10.1111/codi.13207

Cited by 132 publications

(123 citation statements)

References 103 publications

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“…Complete pathologic response occurred in 14 patients (28%), 22 patients (44%) had a partial response and 14 patients (28%) had no response to neoadjuvant chemoradiation, which is consistent with previously published studies (7, 15) with the exception of complete pathologic response that was slightly higher in our study (Table 2). The distribution of TS genotype frequencies as related to tumor regression grade (TRG) is shown in Figure 3.…”

Section: Resultssupporting

confidence: 93%

“…Approximately 70% of patients exhibit pathologic downstaging following treatment, 15–20% of patients exhibit complete pathologic response, while 10–15% of patients have no pathologic response to 5-FU treatment (7) . Currently, response to nCRT is most commonly assessed following completion of treatment by physical examination, magnetic resonance imaging or computed tomography scan.…”

Section: Introductionmentioning

confidence: 99%

“…There are presently no accurate biomarkers to predict a patient’s response to 5-FU based preoperative neoadjuvant treatment (7) . Therefore, patients who have a complete pathologic response with no remaining viable cancer cells may be exposed to unnecessary surgery.…”

Section: Introductionmentioning

confidence: 99%

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Genetic polymorphisms in 5-Fluorouracil–related enzymes predict pathologic response after neoadjuvant chemoradiation for rectal cancer

Nelson

Carter

Eichenberger

et al. 2016

Surgery

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Background Patients with rectal cancer undergo preoperative neoadjuvant chemoradiation with approximately 70% exhibiting pathologic down-staging in response to treatment. There is currently no accurate test to predict patients who are likely to be complete responders to therapy. 5-Fluorouracil (5-FU) is regularly used in the neoadjuvant treatment of rectal cancer. Genetic polymorphisms affect the activity of thymidylate synthase (TS), an enzyme involved in 5-FU metabolism. This may account for observed differences in response to neoadjuvant treatment between patients. Detection of such polymorphisms might identify patients likely to have a complete response to neoadjuvant therapy and perhaps allow them to avoid surgery. Methods DNA was isolated from whole blood taken from patients with newly diagnosed rectal cancer who received neoadjuvant therapy (n=50). Response to therapy was calculated with a tumor regression score, based upon histology, from the time of surgery. PCR was performed targeting the promoter region of TS. PCR products were separated using electrophoresis to determine whether patients were homozygous for a double-tandem repeat (2R), a triple-tandem repeat (3R), or heterozygous (2R/3R). A single nucleotide polymorphism (SNP), 3G or 3C, may also be present in the second repeat unit of the 3R allele. Restriction fragment length polymorphism assays were performed in patients with at least one 3R allele using HaeIII. Results Patients with at least one TS 3G allele were more likely to have complete or partial pathological response to 5-FU neoadjuvant therapy (OR 10.4 95% CI 1.3–81.6) (p=0.01) than those without at least one 3G allele. Conclusions Identification of patients with specific genetic polymorphisms in enzymes involved in 5-FU metabolism appears to predict the likelihood of complete or partial pathologic response of rectal cancer to preoperative neoadjuvant therapy.

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Section: Resultssupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

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Genetic polymorphisms in 5-Fluorouracil–related enzymes predict pathologic response after neoadjuvant chemoradiation for rectal cancer

Nelson

Carter

Eichenberger

et al. 2016

Surgery

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“…Imaging modalities including positron emission tomography-computed tomography, magnetic resonance imaging (MRI) and endoscopic ultrasound are currently used for pretreatment staging, assessment of response to nCRT, and restaging after nCRT [25,26,27,28,29,30,31,32]. Findings from these imaging modalities, including tumor regression rates and circumferential resection margin, can potentially predict response to nCRT in rectal cancer [30,31,32,33]. However the utility of these clinicopathological and radiological features are currently limited due to low sensitivity and specificity.…”

Section: Introductionmentioning

confidence: 99%

Predictive and Prognostic Molecular Biomarkers for Response to Neoadjuvant Chemoradiation in Rectal Cancer

Dayde

Tanaka

Jain

et al. 2017

IJMS

144

152

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Abstract:The standard of care in locally advanced rectal cancer is neoadjuvant chemoradiation (nCRT) followed by radical surgery. Response to nCRT varies among patients and pathological complete response is associated with better outcome. However, there is a lack of effective methods to select rectal cancer patients who would or would not have a benefit from nCRT. The utility of clinicopathological and radiological features are limited due to lack of adequate sensitivity and specificity. Molecular biomarkers have the potential to predict response to nCRT at an early time point, but none have currently reached the clinic. Integration of diverse types of biomarkers including clinicopathological and imaging features, identification of mechanistic link to tumor biology, and rigorous validation using samples which represent disease heterogeneity, will allow to develop a sensitive and cost-effective molecular biomarker panel for precision medicine in rectal cancer. Here, we aim to review the recent advance in tissue-and blood-based molecular biomarker research and illustrate their potential in predicting nCRT response in rectal cancer.

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“…Because response to pCRT correlates to positive survival outcomes4, it is necessary to investigate the mechanisms of pCRT response in LARCs. A common approach for investigating mechanisms of pCRT response is firstly identifying differentially expressed (DE) genes between the non-responders and responders567891011121314151617. However, such DE genes may have various origins.…”

mentioning

confidence: 99%

Discriminating cancer-related and cancer-unrelated chemoradiation-response genes for locally advanced rectal cancers

Guo

Cheng

et al. 2016

Sci Rep

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For patients with locally advanced rectal cancer (LARC) treated with preoperation chemoradiation (pCRT), identifying differentially expressed (DE) genes between non-responders and responders is a common approach for investigating mechanisms of chemoradiation resistance. However, some of such DE genes might be irrelevant to cancer itself but simply reflect the pharmacokinetic differences of the normal tissues. In this study, we adopted the RankComp algorithm to identify DE genes for each of LARC sample compared with its own normal state. Then, we identified genes with significantly different deregulation frequencies between the non-responders and responders, defined as cancer-related pCRT-response genes. Pathway enrichment and protein-protein interaction analyses showed that these genes specifically and intensively interacted with currently known effective genes of pCRT, involving in DNA replication, cell cycle and DNA repair. In contrast, after excluding the cancer-related pCRT-response genes, the other DE genes between non-responders and responders were enriched in many pathways of drug and protein metabolisms and transports, and interacted with both the known effective genes and pharmacokinetic genes. Hence, these two types of DE genes should be distinguished for investigating mechanisms of pCRT response in LARCs.

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Predicting pathological complete response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer: a systematic review

Cited by 132 publications

References 103 publications

Genetic polymorphisms in 5-Fluorouracil–related enzymes predict pathologic response after neoadjuvant chemoradiation for rectal cancer

Genetic polymorphisms in 5-Fluorouracil–related enzymes predict pathologic response after neoadjuvant chemoradiation for rectal cancer

Predictive and Prognostic Molecular Biomarkers for Response to Neoadjuvant Chemoradiation in Rectal Cancer

Discriminating cancer-related and cancer-unrelated chemoradiation-response genes for locally advanced rectal cancers

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