A Review of Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer

Li, Yang; Wang, Ji; Ma, Xiaowei; Tan, Li Tee; Yan, Yanli; Xue, Chaofan; Hui, Baojun; Li, Rui; Ma, Hailin; Ren, Juan

doi:10.7150/ijbs.15438

Cited by 197 publications

(143 citation statements)

References 63 publications

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“…We suggested that stage III rectal SRCC should be arranged for PRT. It could reduce the tumour volume and may facilitate the tumour resection, block the tumour invasion like lymph nodes metastasis or mesorectal fascia threatened, and reduce the local recurrence rate37.…”

Section: Discussionmentioning

confidence: 99%

Prognosis and value of preoperative radiotherapy in locally advanced rectal signet-ring cell carcinoma

Chen

Wang

et al. 2017

Sci Rep

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As well known, signet-ring cell carcinoma (SRCC) is a rare histological subtype of colorectal adenocarcinoma, which has been associated with poor prognosis and resistant to non-surgery therapy compared with common adenocarcinoma. In this study, we assessed the effect of preoperative radiotherapy (PRT) for locally advanced rectal SRCC in a large patient group from the Surveillance, Epidemiology, and End Results program (SEER, 1988–2011) database. SRCC was found in 0.9% (n = 622) rectal cancer (RC) patients in our study. In the PRT setting, SRCC had significantly worse cancer-specific survival than mucinous adenocarcinoma and nonmucinous adenocarcinoma patients (log-rank, P < 0.001). In terms of SRCC, stage III RC patients benefited from PRT (log-rank, P < 0.001) while stage II did not (P = 0.095). The multivariate Cox proportional hazard model showed that PRT was an independent benefit factor in stage III rectal SRCC patients (HR, 0.611; 95% CI, 0.407–0.919; P = 0.018). In conclusion, SRCC was an independent predictor of poor prognosis in stage III RC patients, but not in stage II. In the PRT setting of locally advanced RC, SRCC patients had significantly worse prognosis. PRT was an independent prognostic factor associated with improved survival in stage III rectal SRCC.

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Section: Discussionmentioning

confidence: 99%

Prognosis and value of preoperative radiotherapy in locally advanced rectal signet-ring cell carcinoma

Chen

Wang

et al. 2017

Sci Rep

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“…Surgical resection is an efficient option to treat earlier stages of CRC, but, most patients have been diagnosed at higher and advanced stages of the disease. Over the past decade chemoradiation therapy (CRT), synergistic effects of chemotherapy drugs and radiation, often in combination with surgery have been used as an effective CRC treatment for patients with Stages II and III (Li et al, ). Although, the use of CRT before surgical resection have yielded decreased risk for recurrence, shrinking tumor size, and also a better prognosis, but in over 90% of patients with higher stages of the disease the success rate faced with failure because of resistance to treatment (Geng & Wang, ).…”

Section: Introductionmentioning

confidence: 99%

Let‐7e enhances the radiosensitivity of colorectal cancer cells by directly targeting insulin‐like growth factor 1 receptor

Samadi

Afshar

Amini

et al. 2018

Journal Cellular Physiology

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Abnormal expression of various microRNAs (miRNAs), as regulators of biological signaling pathways, has a strong association with cancer resistance to chemotherapy and radiotherapy. The let‐7 family of miRNAs as tumor suppressors have shown to be downregulated in different types of human malignancies including colorectal cancer (CRC). However, the biological function of let‐7 members in the processes of resistance to radiation in CRC has not yet been completely elucidated. Insulin‐like growth factor 1 receptor (IGF‐1R) signaling pathway is amplified in CRC and leads to its progression, development, and also radiation resistance. So, it seems like an attractive target for anticancer therapy. In this study, by using bioinformatics analysis, it has been revealed that IGF‐1R is a direct target of the let‐7e member. Consistent with this, we identified that increased levels of let‐7e in CRC cells reduced IGF‐1R protein level and subsequently its downstream signaling pathways, which resulted in the G1 cell cycle arrest and a significant reduction in the proliferation, survival and also resistance to radiation of CRC cells. Altogether, these results suggested that let‐7e by targeting the IGF‐1R signaling pathway might serve as therapeutics in anticancer therapy.

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“…Furthermore, nRCTx leads to a decrease of the tumor mass, allowing for a higher rate of sphincter sparing surgical methods and a higher rate of R0-resections. 4,5 The histological tumor regression (TRG) grade according to Dworak 6 serves as a system to categorize therapy-induced effects within rectal cancers after nRCTx. 7 Studies demonstrated the clinical relevance as a prognostic factor showing improved disease-free survival after pathologic response.…”

Section: Introductionmentioning

confidence: 99%

Neoadjuvant radiochemotherapy decreases the total amount of tumor infiltrating lymphocytes, but increases the number of CD8+/Granzyme B+ (GrzB) cytotoxic T-cells in rectal cancer

et al. 2017

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Although neoadjuvant radiochemotherapy (nRCTx) is an established oncological treatment in patients with advanced rectal cancer, little is known about its effects on the tumor microenvironment. Quantity and composition of tumor infiltrating lymphocytes (TILs) are known to influence patients' prognosis but nRCTx-induced modifications are still unclear. We determined the composition of the immune cell infiltrate in rectal cancer after nRCTx and its influence on tumor regression, local recurrence rate and survival. We investigated density and composition of tumor infiltrating CD3 and CD8 T-cells and the quantity and ratio of CD8/GrzB T-cells to CD8 T-cells in 130 rectal cancers after nRCTx compared to a cohort of 30 primarily resected rectal cancers. Furthermore, we analyzed 22 pretherapeutic rectal cancer biopsies, later treated with nRCTx and surgery to evaluate nRCTx-induced modifications of the tumor microenvironment. The total numbers of CD3 and CD8 T-cells in tumor stroma (p < 0.001) and tumor epithelium (p < 0.001 CD3; 0.002 CD8) were significantly lower in rectal cancers after nRCTx compared to primarily resected cases, while the ratio of CD8/GrzB T-cells to CD8 T-cells was significantly increased in the nRCTx cohort (p < 0.001). In multivariate analyses, CD8/GrzB T-cells in the tumor stroma were significantly associated with high regression grade and a lower likelihood of local recurrence (p = 0.029). nRCTx modifies the tumor microenvironment of rectal cancer leading to a total decrease of TILs, but a relative increase in CD8/GrzB T-cells in the tumor stroma. CD8/GrzB T-cells may contribute to local tumor control and the better outcome.

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A Review of Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer

Cited by 197 publications

References 63 publications

Prognosis and value of preoperative radiotherapy in locally advanced rectal signet-ring cell carcinoma

Prognosis and value of preoperative radiotherapy in locally advanced rectal signet-ring cell carcinoma

Let‐7e enhances the radiosensitivity of colorectal cancer cells by directly targeting insulin‐like growth factor 1 receptor

Neoadjuvant radiochemotherapy decreases the total amount of tumor infiltrating lymphocytes, but increases the number of CD8+/Granzyme B+ (GrzB) cytotoxic T-cells in rectal cancer

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