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.

Pathological Complete Response After Neoadjuvant Therapy in Rectal Adenocarcinoma: a 5-Year Follow-up

“…Young age is a reported predictive factor of lower pCR rate following neoadjuvant therapy [29]. Our study population reported a relatively younger patient population who underwent neoadjuvant therapy, which possibly explains the low pCR rate in our study population.…”

“…Our study population reported a relatively younger patient population who underwent neoadjuvant therapy, which possibly explains the low pCR rate in our study population. It was postulated that these younger patients had more aggressive pathological features, believed to be associated with a higher CD133+ cancer stem cell burden, which contributed to poorer response to neoadjuvant therapy [29]. This warrants more research to evaluate the need to optimize the neoadjuvant therapy in young patients.…”

Associations between clinical characteristics and tumor response to neoadjuvant chemoradiotherapy in rectal cancer

“…Therefore, the genomics analysis was not conducted in our research, although some biologically predictive characteristics have been explored in previous studies. 11 , 25 , 31 , 32 , 33 Besides, the chemotherapy regimens in this study were not consistent, and the response assessment might influence the number of chemotherapy cycles during treatment. Therefore, we reduced this limitation by enrolling a considerable number of patients and conducted PSM analysis to balance the differences.…”

The Survival Effect of Radiotherapy on Stage II/III Rectal Cancer in Different Age Groups: Formulating Radiotherapy Decision-Making Based on Age

“…Mismatched biology may be responsible for the inconsistent survival benefits among different age groups. A recent research study reported that young rectal cancer patients have a higher proportion of cancer stem cells (CSCs) ( 29 ), which is considered as an important factor reflecting radiotherapy resistance in rectal cancer ( 30 , 31 ). In addition, we took out stage II RC patients separately for analysis and got similar results comparing to the total stage II/III RC patients ( Supplementary Files ).…”