Locally advanced rectal adenocarcinoma: Treatment sequences, intensification, and rectal organ preservation

Bigness, Alec; Imanirad, Iman; Şahin, Ibrahim Halil; Xie, Hao; Frakes, Jessica M.; Hoffe, Sarah E.; Laskowitz, Danielle; Felder, Seth

doi:10.3322/caac.21661

Cited by 16 publications

(9 citation statements)

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“…The 5-year survival rates of colorectal cancer were approximately 65% (1). The primary therapeutic approach for early-stage colorectal cancer is surgical resection, and a combination of chemotherapy and targeted therapy may improve the prognosis of patients with advanced-stage disease (2)(3)(4). A subset of patients also responded to immunotherapy that targets PD-1 or CTLA-4 checkpoints (5)(6)(7)(8), suggesting the critical role of the tumor immune microenvironment (TME) in the progression and treatment of colorectal cancer.…”

Section: Introductionmentioning

confidence: 99%

Integrated single-cell RNA-seq analysis identifies immune heterogeneity associated with KRAS/TP53 mutation status and tumor-sideness in colorectal cancers

Liu

et al. 2022

Front. Immunol.

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BackgroundThe main objective of this study was to analyze the effects of KRAS/TP53 mutation status and tumor sideness on the immune microenvironment of colorectal cancer using integrated scRNA-seq data.MethodsA total of 78 scRNA-seq datasets, comprising 42 treatment-naive colorectal tumors, 13 tumor adjacent tissues and 23 normal mucosa tissues were included. Standardized Seurat procedures were applied to identify cellular components with canonical cell marks. The batch-effect was assessed and corrected using harmony algorithm. The scMetabolism algorithm was used for single-cell metabolic analysis. The results and clinical significance were further validated using immunofluorescent-staining and TCGA-COAD datasets. Immune-infiltration scores of bulk-RNA-seq data were estimated using ssGSEA. The presto-wilcoxauc algorithm was used to identify differentially enriched genes or pathways across different subgroups. Two-sided p-value less than 0.05 was considered statistically significant.ResultsWe refined the landscape of functional immune cell subtypes, especially T cells and myeloid cells, across normal mucosa, tumor adjacent and tumor tissue. The existence and function of two states of exhausted CD8+ T (Tex) subtypes in colorectal cancer, and FOLR2+ LYVE1+ macrophages indicating unfavorable prognosis in colorectal cancer were identified and validated. The diverse tumor mutation status reshaped the immune cell function and immune checkpoint ligands/receptors (ICLs/ICRs) expression pattern. Importantly, the KRAS/TP53 dual mutations significantly reduced the major energy metabolic functions in immune cells, and promoted the cell-to-cell communications towards immunosuppression in colorectal cancers. The results revealed LAG3, CD24-SIGLEC10 and HBEGF-CD9 pathways as potential therapeutic targets for dual mutant colorectal cancers.ConclusionsWe revealed that the immune microenvironment underwent a gradual remodeling with an enrichment of immunosuppressive myeloid cells from normal mucosa to tumor regions in colorectal cancers. Moreover, we revealed the metabolic heterogeneity of tumor-infiltrating immune cells and suggested that the KRAS/TP53 dual mutation may impair antitumor immunity by reducing T and myeloid cell energy metabolism and reshaping cellular interactions toward immunosuppression.

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Section: Introductionmentioning

confidence: 99%

Integrated single-cell RNA-seq analysis identifies immune heterogeneity associated with KRAS/TP53 mutation status and tumor-sideness in colorectal cancers

Liu

et al. 2022

Front. Immunol.

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“…Unfortunately, the incorporation of oxaliplatin, irinotecan, biological agents (such as antivascular endothelial growth factor [bevacizumab] or antiepidermal growth factor receptors [cetuximab]), and PARP (poly[ADP]‐ribose polymerase) inhibitors in concurrent chemoradiotherapy regimens has not been found to improve the pathological complete response (pCR) or systemic recurrence rates 4–11 . The addition of neoadjuvant chemotherapy that is delivered prior to or after chemoradiotherapy has shown a reduction in the incidence of distant recurrences in recent studies; however, overall survival data are still pending 12–16 . Several attempts have been made to reduce the recurrence rate through adjuvant chemotherapy, however, this has not been shown to improve the results primarily because of reduced compliance 17–19 …”

Section: Introductionmentioning

confidence: 99%

“…[4][5][6][7][8][9][10][11] The addition of neoadjuvant chemotherapy that is delivered prior to or after chemoradiotherapy has shown a reduction in the incidence of distant recurrences in recent studies; however, overall survival data are still pending. [12][13][14][15][16] Several attempts have been made to reduce the recurrence rate through adjuvant chemotherapy, however, this has not been shown to improve the results primarily because of reduced compliance. [17][18][19] Gemcitabine is a well-known radiosensitizer.…”

Section: Introductionmentioning

confidence: 99%

Neoadjuvant concurrent chemoradiotherapy using infusional gemcitabine in locally advanced rectal cancer: A phase II trial

et al. 2022

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“…Secondary hemorrhage of advanced colorectal cancer is one of the most common complications of this disease (1)(2)(3). Because most patients with advanced cancer are complicated with distant organ metastasis or weak constitution after multiple radiotherapy and chemotherapy cycles, they are unable to undergo further surgical intervention (4,5). Moreover, as the hemostatic effect of internal medicine is not immediately apparent, interventional embolization hemostasis is the most effective method for the treatment of secondary bleeding of advanced colorectal cancer (6)(7)(8), which both prolongs survival and greatly improves patients' quality life (9,10).…”

Section: Introductionmentioning

confidence: 99%

Multiple interventional embolizations for hemostasis in hemorrhage following advanced colorectal cancer treatment: a case report

Yang

Shi

et al. 2022

J Gastrointest Oncol

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Background: In recent years, the incidence of serious complications in patients with advanced colorectal cancer has been progressively increasing, and the fatality rate of secondary bleeding is the highest, while most patients cannot undergo surgical intervention due to physical weakness, while interventional embolization therapy has attracted more and more attention of clinicians because of its advantages of small trauma and quick effect. Among them, multiple cases of secondary hemorrhage of different arteries are very rare. In this case, the changes of vital signs of patients were significantly stabilized after each interventional embolization therapy. Interventional embolization therapy can be used as one of the first choices for secondary hemorrhage.Case Description: Retrospectively analyzed the clinical data of a patient with advanced colorectal cancer who successively developed 7 times of secondary hemorrhage within 10 months. The two times of hemorrhage had different degrees of hemorrhagic shock, and five times showed unexplained progressive decrease in hemoglobin. The location of each hemorrhage and the arteries invaded by the tumor were different, and the embolization materials and treatment methods used each time were not the same. The effect of interventional embolization each time could effectively stop bleeding, and the patient greatly improved the quality of life with tumor survival. The patient prolonged the survival cycle for up to 16 months from the first secondary hemorrhage.Conclusions: For patients with advanced colorectal cancer complicated with secondary hemorrhage, interventional embolization can be used to control the disease and prolong the life cycle, which is one of the preferred treatment methods in clinical application.

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Locally advanced rectal adenocarcinoma: Treatment sequences, intensification, and rectal organ preservation

Abstract: underwent ileostomy reversal in June 2020. He is currently under surveillance with normal CEA and no radiographic evidence of disease. He experiences urgency and clustering of bowel movements, consistent with low anterior resection syndrome.

Cited by 16 publications

References 65 publications

Integrated single-cell RNA-seq analysis identifies immune heterogeneity associated with KRAS/TP53 mutation status and tumor-sideness in colorectal cancers

Integrated single-cell RNA-seq analysis identifies immune heterogeneity associated with KRAS/TP53 mutation status and tumor-sideness in colorectal cancers

Neoadjuvant concurrent chemoradiotherapy using infusional gemcitabine in locally advanced rectal cancer: A phase II trial

Multiple interventional embolizations for hemostasis in hemorrhage following advanced colorectal cancer treatment: a case report

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