A Comprehensive Evaluation of Associations Between Routinely Collected Staging Information and The Response to (Chemo)Radiotherapy in Rectal Cancer

Hammarström, Klara; Imam, Israa; Mezheyeuski, Artur; Ekström, Joakim; Sjöblom, Tobias; Glimelius, Bengt

doi:10.3390/cancers13010016

Cited by 25 publications

(41 citation statements)

References 53 publications

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“…In the mucinous group, no significant differences were found between SCRT and LCRT for survival outcomes [76]. Similarly, a retrospective review by Hammarström found mucinous rectal cancers were more likely to be treated with NACRT or SCRT with additional chemotherapy [77]. There was no difference in pCR rate observed between mucinous and non-mucinous rectal cancers overall [77].…”

Section: Radiotherapy Resistance In Mucinous Colorectal Cancermentioning

confidence: 95%

“…Similarly, a retrospective review by Hammarström found mucinous rectal cancers were more likely to be treated with NACRT or SCRT with additional chemotherapy [77]. There was no difference in pCR rate observed between mucinous and non-mucinous rectal cancers overall [77]. However, no mucinous rectal cancer receiving SCRT alone achieved pCR, but addition of chemotherapy to SCRT improved the pCR rate [77].…”

Section: Radiotherapy Resistance In Mucinous Colorectal Cancermentioning

confidence: 98%

“…There was no difference in pCR rate observed between mucinous and non-mucinous rectal cancers overall [77]. However, no mucinous rectal cancer receiving SCRT alone achieved pCR, but addition of chemotherapy to SCRT improved the pCR rate [77]. Overall, there appears to be a dearth of prospective data comparing radiotherapy approaches for LARC mucinous rectal cancer with evidence heavily reliant on heterogenous database studies.…”

Section: Radiotherapy Resistance In Mucinous Colorectal Cancermentioning

confidence: 99%

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Resistance to Cell Death in Mucinous Colorectal Cancer—A Review

OʼConnell

Reynolds

McNamara

et al. 2021

Cancers

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Mucinous colorectal cancer (CRC) is estimated to occur in approximately 10–15% of CRC cases and is characterized by abundant extracellular mucin. Mucinous CRC is frequently associated with resistance to apoptosis. Inferior prognosis is observed in mucinous CRC, particularly in rectal cancer and metastatic cases. Mucins are heavily glycosylated secretory or transmembrane proteins that participate in protection of the colonic epithelium. MUC2 overexpression is a hallmark of mucinous CRCs. Mucinous CRC is associated with KRAS and BRAF mutation, microsatellite instability and the CpG island methylator phenotype. Mutations of the APC gene and p53 mutations which are characteristic non-mucinous colorectal adenocarcinoma are less common in mucinous CRC. Both physical and anti-apoptotic properties of mucin provide mechanisms for resistance to cell death. Mucin glycoproteins are associated with decreased expression of pro-apoptotic proteins, increased expression of anti-apoptotic proteins and increased cell survival signaling. The role for BCL-2 proteins, including BCL-XL, in preventing apoptosis in mucinous CRC has been explored to a limited extent. Additional mechanisms opposing cell death include altered death receptor expression and altered mutation rates in genes responsible for chemotherapy resistance. The roles of alternate cell death programs including necroptosis and pyroptosis are not well understood in mucinous CRC. While the presence of MUC2 is associated with an immunosuppressive environment, the tumor immune environment of mucinous CRC and the role of immune-mediated tumor cell death likewise require further investigation. Improved understanding of cell death mechanisms in mucinous CRC may allow modification of currently used regimens and facilitate targeted treatment.

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Section: Radiotherapy Resistance In Mucinous Colorectal Cancermentioning

confidence: 95%

Section: Radiotherapy Resistance In Mucinous Colorectal Cancermentioning

confidence: 98%

Section: Radiotherapy Resistance In Mucinous Colorectal Cancermentioning

confidence: 99%

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Resistance to Cell Death in Mucinous Colorectal Cancer—A Review

OʼConnell

Reynolds

McNamara

et al. 2021

Cancers

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“…Hammarström et al reported that tumor length had an AUC of only 0.599 for predicting pCR. 17 In this study, tumor length and clinical T stage exhibited AUCs of 0.578 and 0.561 for predicting a bad response, respectively. Serum biomarkers are safe and convenient indices which could indirectly reflect dynamic interactions between tumor and host, and may assist in response prediction.…”

Section: Discussionmentioning

confidence: 54%

Serum Apolipoprotein A-I Predicts Response of Rectal Cancer to Neoadjuvant Chemoradiotherapy

Guo

Chen

Zeng

et al. 2021

CMAR

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Background: Serum lipids have been reported as prognosticators for malignancies, including rectal cancer (RC). Yet, their value in predicting the response of RC to neoadjuvant chemoradiotherapy (NACRT) remains unknown. This study aimed to assess the predictive abilities of serum lipids for a bad response, and to build a serum lipid-based prediction model. Methods: In total, 751 patients diagnosed with stage cII-III RC and treated with NACRT plus surgery from January 2007 to August 2018 were retrospectively reviewed and randomly divided into two data sets, in a ratio of 1:1. Receiver operating characteristics (ROC) analysis was conducted in the development set to select possible predictors of bad NACRT response from pathoclinical factors, including serum lipids. Multivariate logistic regression was conducted to further determine independent predictors, which were then used to develop a prediction index (PI). Finally, the PI was verified in the validation set, through ROC analysis and chi-squared test. Results: Five independent predictors were identified: tumor length ≥4 cm, cT4 stage, carcinoembryonic antigen ≥5.0 ng/mL, irradiation with three-dimensional conformal radiotherapy technique, and apolipoprotein A-I ≤1.20 g/L. Each of them was assigned a number of points. In the validation set, the area under the curve of PI appeared as 0.642 (95% confidence interval 0.586-0.697). The sensitivity, specificity, positive and negative predictive values, and concordance were 72.3%, 52.3%, 63.8%, 61.9%, and 63.0%, respectively. Conclusion: Serum apolipoprotein A-I was found to correlate negatively with the RC response to NACRT. It could serve as a biomarker for guiding individualized treatment and a potential target for improving sensitivity to chemoradiation.

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“…6,9,10 Thus, the interest in investigating the primary clinicopathological tumor characteristics and treatment strategies that predict a pathological good response is growing, since these aspects may influence the choices of preoperative treatments and subsequent management techniques in the future. 8,[11][12][13] Several prospective clinical trials have investigated the scheduling of nCRT. [14][15][16][17] Gao et al suggested that the sandwich treatment approach, involving induction, concurrent, and consolidation chemotherapy, would result in a 42.2% of pCR rate and 82.2% of downstaging.…”

Section: Introductionmentioning

confidence: 99%