Worse treatment response to neoadjuvant chemoradiotherapy in young patients with locally advanced rectal cancer

Abstract Background: To evaluate the impact of age on the efficacy of neoadjuvant chemoradiotherapy (NCRT) in patients with locally advanced rectal cancer (LARC).Method: LARC patients undergoing NCRT and radical surgery from 2011 to 2018 were divided into young (<40 years) and old (≥40 years) groups. Multivariate analyses were performed to identify predictive factors for pathological complete response (pCR). Predictive nomograms and decision curve analysis were used to compare the models including/excluding age groups. Immunohistochemical analysis was performed to detect CD133 expression in LARC patients.Result: A total of 901 LARC patients were analyzed. The young group was associated with poorly differentiated tumors, more metastatic lymph nodes, higher perineural invasion, and a lower tumor regression grade (P = 0.008; P < 0.001; P < 0.001; P = 0.003). Logistic regression analysis demonstrated that age <40 years (HR = 2.190, P = 0.044), tumor size (HR = 0.538, P < 0.001), pre-NCRT cN stage (HR = 0.570, P = 0.036), and post-NCRT CEA level (HR = 0.877, P = 0.001) were significantly associated with pCR. Predictive nomograms and decision curve analysis demonstrated that the predictive ability of models including the age group was superior to that of models excluding the age group. Higher CD133 expression was more common in young LARC patients.Conclusion: Young patients with LARC were associated with lower pCR rates following NCRT. The ability of the predictive model was greater when based on the age group. Young LARC patients were associated with a higher CD133+ tumor stem cell burden, which contributed to the lower pCR rates.

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Worse treatment response to neoadjuvant chemoradiotherapy in young patients with locally advanced rectal cancer

10.21203/rs.2.20268/v2 ◽

2020 ◽

Author(s):

Yiyi Zhang ◽

Meifang Xu ◽

Yong Wu ◽

Shoufeng Li ◽

Xing Liu ◽

...

Keyword(s):

Rectal Cancer ◽

Locally Advanced ◽

Neoadjuvant Chemoradiotherapy ◽

Young Patients ◽

Advanced Rectal Cancer ◽

Locally Advanced Rectal Cancer ◽

Curve Analysis ◽

Age Group ◽

Decision Curve Analysis ◽

Cd133 Expression

Abstract Background: To evaluate the impact of age on the efficacy of neoadjuvant chemoradiotherapy (NCRT) in patients with locally advanced rectal cancer (LARC).Method: LARC patients undergoing NCRT and radical surgery from 2011 to 2018 were divided into young (<40 years) and old (≥40 years) groups. Multivariate analyses were performed to identify predictive factors for pathological complete response (pCR). Predictive nomograms and decision curve analysis were used to compare the models including/excluding age groups. Immunohistochemical analysis was performed to detect CD133 expression in LARC patients.Result: A total of 901 LARC patients were analyzed. The young group was associated with poorly differentiated tumors, more metastatic lymph nodes, higher perineural invasion, and a lower tumor regression grade (P = 0.008; P < 0.001; P < 0.001; P = 0.003). Logistic regression analysis demonstrated that age <40 years (HR = 2.190, P = 0.044), tumor size (HR = 0.538, P < 0.001), pre-NCRT cN stage (HR = 0.570, P = 0.036), and post-NCRT CEA level (HR = 0.877, P = 0.001) were significantly associated with pCR. Predictive nomograms and decision curve analysis demonstrated that the predictive ability of models including the age group was superior to that of models excluding the age group. Higher CD133 expression was more common in young LARC patients.Conclusion: Young patients with LARC were associated with lower pCR rates following NCRT. The ability of the predictive model was greater when based on the age group. Young LARC patients were associated with a higher CD133+ tumor stem cell burden, which contributed to the lower pCR rates.

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Worse treatment response to neoadjuvant chemoradiotherapy in young patients with locally advanced rectal cancer

10.21203/rs.2.20268/v1 ◽

2020 ◽

Author(s):

Yiyi Zhang ◽

Meifang Xu ◽

Yong Wu ◽

Shoufeng Li ◽

Xing Liu ◽

...

Keyword(s):

Rectal Cancer ◽

Locally Advanced ◽

Neoadjuvant Chemoradiotherapy ◽

Young Patients ◽

Advanced Rectal Cancer ◽

Locally Advanced Rectal Cancer ◽

Curve Analysis ◽

Age Group ◽

Decision Curve Analysis ◽

Cd133 Expression

Abstract Background To evaluate the impact of age on the efficacy of neoadjuvant chemoradiotherapy (NCRT) in patients with locally advanced rectal cancer (LARC) and explore the underlying mechanism.Method LARC patients undergoing NCRT and radical surgery from 2011 to 2018 were divided into young (<40 years) and old (≥40 years) groups. Multivariate analyses were performed to identify predictive factors for pathological complete response (pCR). Predictive nomograms and decision curve analysis were used to compare the models including/excluding age groups. Immunohistochemical analysis was performed to detect CD133 expression in LARC patients.Result A total of 901 LARC patients were analyzed. The young group was associated with poorly differentiated tumors, more metastatic lymph nodes, higher perineural invasion, and a lower tumor regression grade (P = 0.008; P < 0.001; P < 0.001; P = 0.003). Logistic regression analysis demonstrated that age <40 years (HR = 2.190, P = 0.044), tumor size (HR = 0.538, P < 0.001), pre-NCRT cN stage (HR = 0.570, P = 0.036), and post-NCRT CEA level (HR = 0.877, P = 0.001) were significantly associated with pCR. Predictive nomograms and decision curve analysis demonstrated that the predictive ability of models including the age group was superior to that of models excluding the age group. Higher CD133 expression was more common in young LARC patients.Conclusion Young patients with LARC were associated with lower pCR rates following NCRT. The ability of the predictive model was greater when based on the age group. Young LARC patients were associated with a higher CD133+ tumor stem cell burden, which contributed to the lower pCR rates.

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Worse prognosis in young patients with locally advanced rectal cancer following neoadjuvant chemoradiotherapy

Medicine ◽

10.1097/md.0000000000021304 ◽

2020 ◽

Vol 99 (35) ◽

pp. e21304

Author(s):

Yiyi Zhang ◽

Ye Wang ◽

Xing Liu ◽

Bin Chen ◽

Jinfu Zhuang ◽

...

Keyword(s):

Rectal Cancer ◽

Locally Advanced ◽

Neoadjuvant Chemoradiotherapy ◽

Young Patients ◽

Advanced Rectal Cancer ◽

Locally Advanced Rectal Cancer ◽

Worse Prognosis

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Worse treatment response to neoadjuvant chemoradiotherapy in young patients with locally advanced rectal cancer

BMC Cancer ◽

10.1186/s12885-020-07359-2 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Yiyi Zhang ◽

Liangliang Yan ◽

Yong Wu ◽

Meifang Xu ◽

Xing Liu ◽

...

Keyword(s):

Rectal Cancer ◽

Treatment Response ◽

Locally Advanced ◽

Neoadjuvant Chemoradiotherapy ◽

Young Patients ◽

Advanced Rectal Cancer ◽

Locally Advanced Rectal Cancer

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Predicting response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer with serum biomarkers

Annals of The Royal College of Surgeons of England ◽

10.1308/rcsann.2017.0030 ◽

2017 ◽

Vol 99 (5) ◽

pp. 373-377 ◽

Cited By ~ 7

Author(s):

TL Clarke ◽

DA White ◽

ME Osborne ◽

AM Shaw ◽

NJ Smart ◽

...

Keyword(s):

Rectal Cancer ◽

Pathological Complete Response ◽

Locally Advanced ◽

Neoadjuvant Chemoradiotherapy ◽

Complete Response ◽

Advanced Rectal Cancer ◽

Locally Advanced Rectal Cancer ◽

Serum Biomarkers ◽

Curve Analysis ◽

Roc Curve Analysis

Introduction The aim of this study was to identify patient factors including serum biomarkers that may predict response to neoadjuvant chemoradiotherapy (CRT) in patients with locally advanced rectal cancer staged on magnetic resonance imaging. Prediction of response may be helpful when selecting patients for a non-operative programme. Methods A retrospective review was carried out of patients undergoing neoadjuvant CRT for rectal cancer, conducted at the Royal Devon and Exeter Hospital. All patients were managed through the multidisciplinary team. Receiver operating characteristic (ROC) curve analysis was undertaken to assess the ability of biomarkers to predict response to neoadjuvant CRT. The biomarkers assessed included neutrophils, lymphocytes, monocytes, haemoglobin, platelets, C-reactive protein and carcinoembryonic antigen. Results Seventy-three patients underwent neoadjuvant CRT between January 2006 and December 2011. Nine (12.3%) of these experienced a clinical complete response and were managed with a ‘watch and wait’ approach. An additional ten patients (13.7%) had a pathological complete response following surgery. Using ROC curve analysis, the biomarkers with the largest area under the curve (AUC) were pre-CRT haemoglobin and post-CRT lymphocyte concentrations, producing AUC values of 0.673 and 0.618 respectively for clinical complete response. Pre-CRT haemoglobin and neutrophil concentrations produced the highest AUC values for pathological complete response at 0.591 and 0.614 respectively. Conclusions None of the assessed biomarkers offer the ability to predict response to neoadjuvant CRT in patients with rectal cancer. They cannot therefore assist in identifying complete clinical or pathological responders who could be considered for a non-operative, observational approach.

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Molecular and Dynamic Evaluation of Proteins Related to Resistance to Neoadjuvant Treatment with Chemoradiotherapy in Circulating Tumor Cells of Patients with Locally Advanced Rectal Cancer

Cells ◽

10.3390/cells10061539 ◽

2021 ◽

Vol 10 (6) ◽

pp. 1539

Author(s):

Virgílio Souza e Silva ◽

Emne Ali Abdallah ◽

Bianca de Cássia Troncarelli Flores ◽

Alexcia Camila Braun ◽

Daniela de Jesus Ferreira Costa ◽

...

Keyword(s):

Rectal Cancer ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Transforming Growth Factor ◽

Locally Advanced ◽

Neoadjuvant Treatment ◽

Neoadjuvant Chemoradiotherapy ◽

Disease Free Survival ◽

Advanced Rectal Cancer ◽

Locally Advanced Rectal Cancer

The heterogeneity of response to neoadjuvant chemoradiotherapy (NCRT) is still a challenge in locally advanced rectal cancer (LARC). The evaluation of thymidylate synthase (TYMS) and RAD23 homolog B (RAD23B) expression in circulating tumor cells (CTCs) provides complementary clinical information. CTCs were prospectively evaluated in 166 blood samples (63 patients) with LARC undergoing NCRT. The primary objective was to verify if the absence of RAD23B/TYMS in CTCs would correlate with pathological complete response (pCR). Secondary objectives were to correlate CTC kinetics before (C1)/after NCRT (C2), in addition to the expression of transforming growth factor-β receptor I (TGF-βRI) with survival rates. CTCs were isolated by ISET and evaluated by immunocytochemistry (protein expression). At C1, RAD23B was detected in 54.1% of patients with no pCR and its absence in 91.7% of patients with pCR (p = 0.014); TYMS− was observed in 90% of patients with pCR and TYMS+ in 51.7% without pCR (p = 0.057). Patients with CTC2 > CTC1 had worse disease-free survival (DFS) (p = 0.00025) and overall survival (OS) (p = 0.0036) compared with those with CTC2 ≤ CTC1. TGF-βRI expression in any time correlated with worse DFS (p = 0.059). To conclude, RAD23B/TYMS and CTC kinetics may facilitate the personalized treatment of LARC.

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