Neoadjuvant Immune Checkpoint Inhibition Improves Organ Preservation in T4bM0 Colorectal Cancer With Mismatch Repair Deficiency: A Retrospective Observational Study

Han, Kai; Tang, Jinghua; Liao, Leen; Wu, Jihuai; Sui, Qiaoqi; Xiao, Binyi; Li, Wei-Rong; Hong, Zhigang; Li, Yuan; Kong, Ling Heng; Li, Dandan; Zhang, Xiaoshi; Pan, Zhizhong; Steele, Scott R.; Ding, Pei-Rong

doi:10.1097/dcr.0000000000002466

Cited by 19 publications

(14 citation statements)

References 27 publications

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“…A retrospective study of 245 patients with CRC showed that the incidence of MSI-H was higher in patients with right colon cancer and TNM stage I-II disease (30). Another retrospective analysis of 268 patients with CRC showed a high incidence of dMMR in patients with locally advanced (T4b) tumors without distant metastasis (31). Additionally, a recent analysis of 1,014 patients with CRC (100 [9.8%] with dMMR and 914 [90.2%] with pMMR tumors) indicated that advanced-stage tumors were significantly more common among patients with pMMR CRC than among those with dMMR CRC (stage IV: 21% vs. 3%; P < 0.001) (27).…”

Section: Demographic Characteristics and Msi/mmr Status In Crcsmentioning

confidence: 99%

Clinicopathological characteristics of high microsatellite instability/mismatch repair-deficient colorectal cancer: A narrative review

Mei

Qian

et al. 2022

Front. Immunol.

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Colorectal cancers (CRCs) with high microsatellite instability (MSI-H) and deficient mismatch repair (dMMR) show molecular and clinicopathological characteristics that differ from those of proficient mismatch repair/microsatellite stable CRCs. Despite the importance of MSI-H/dMMR status in clinical decision making, the testing rates for MSI and MMR in clinical practice remain low, even in high-risk populations. Additionally, the real-world prevalence of MSI-H/dMMR CRC may be lower than that reported in the literature. Insufficient MSI and MMR testing fails to identify patients with MSI-H/dMMR CRC, who could benefit from immunotherapy. In this article, we describe the current knowledge of the clinicopathological features, molecular landscape, and radiomic characteristics of MSI-H/dMMR CRCs. A better understanding of the importance of MMR/MSI status in the clinical characteristics and prognosis of CRC may help increase the rates of MMR/MSI testing and guide the development of more effective therapies based on the unique features of these tumors.

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Section: Demographic Characteristics and Msi/mmr Status In Crcsmentioning

confidence: 99%

Clinicopathological characteristics of high microsatellite instability/mismatch repair-deficient colorectal cancer: A narrative review

Mei

Qian

et al. 2022

Front. Immunol.

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“…These findings could indicate tumor downstaging with neoadjuvant chemotherapy. Some research has shown promising results with regard to colon cancer downstaging with NAT 19,20 . However, these results should be examined carefully as the higher proportion of T4 tumors in the SRF group may indicate patients presenting with obstructive or near‐obstructive symptoms and cannot tolerate NAT.…”

Section: Discussionmentioning

confidence: 99%

Neoadjuvant chemotherapy does not increase risk for anastomotic leak for simultaneous resection of primary colon cancer with synchronous liver metastasis: A NSQIP‐colectomy analysis

Mankarious

Portolese

Hoskins

et al. 2023

Journal of Surgical Oncology

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Background and Objectives In patients with colon cancer with synchronous liver metastasis, treatment algorithms are complex and often require multidisciplinary evaluation. Neoadjuvant therapy is frequently utilized, but there is an unclear relationship with postoperative outcomes in patients with simultaneous resection. Methods This is a retrospective cohort study from the National Surgical Quality Improvement Program and Targeted Colectomy databases. All patients with stage IV colon cancer undergoing simultaneous colectomy with synchronous liver metastasis resection or ablation between 2015 and 2019 were identified and categorized into subgroups based on receipt of neoadjuvant chemotherapy. Multivariable logistic regression was utilized to assess for risk factors of anastomotic leaks and serious postoperative complications. Results We identified 1006 patients who underwent simultaneous colectomy and liver operations. Of those, 418 (41.6%) received neoadjuvant chemotherapy within 90 days of surgery, while 588 (58.4%) had simultaneous upfront surgery. On multivariable logistic regression, neoadjuvant therapy was not associated with postoperative anastomotic leaks (odds ratio [OR]: 1.30; p = 0.39) or serious complications (OR: 1.04; p = 0.82). Conclusion Neoadjuvant therapy does not increase postoperative complications in simultaneous colon and liver resections. These results may alleviate concerns regarding postoperative morbidity in the decision‐making process of administering neoadjuvant therapy.

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“…From these, 8 studies met the eligibility criteria. [11][12][13][14][15][16][17][18] No new studies were included in the PubMed search between April and September 2023. A flow diagram is in Supplemental Figure 1 at http://links.…”

Section: Systematic Reviewmentioning

confidence: 99%

Systematic Review of Neoadjuvant Immunotherapy for Mismatch Repair Deficient Locally Advanced Colon Cancer: An Emerging Strategy

Loria,

Ammann,

Olowokure

et al. 2024

Diseases of the Colon &Amp; Rectum

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BACKGROUND: In April 2023, the National Comprehensive Cancer Network endorsed neoadjuvant immunotherapy for select patients with non-metastatic mismatch repair deficient colon cancer. Approximately 15% of incident colon cancers are mismatch repair deficient, resulting in a distinct molecular subtype with high microsatellite instability that is responsive to immune checkpoint inhibition. OBJECTIVE: To describe the existing evidence supporting neoadjuvant immunotherapy for mismatch repair deficient, microsatellite unstable non-metastatic colon cancer. DATA SOURCES: A medical librarian performed PubMed, Embase, and Web of Science searches most recently on April 24, 2023. The PubMed search was re-run on September 26, 2023, to identify any additional studies published during the interim from April to September 2023. STUDY SELECTION: Two authors screened titles and abstracts in the published studies. The inclusion criteria were (1) English-language; (2) adults with primary cancer of the colon; (3) non-metastatic disease; (4) neoadjuvant immunotherapy; (5) reporting on 10 or more cases. INTERVENTION: Neoadjuvant immunotherapy. MAIN OUTCOME MEASUREs: Safety (Grade 3+ treatment related adverse events) and efficacy (complete pathologic responses). RESULTS: From 7,691 studies identified, 6,370 were screened, and 8 included. Various agents, dosing regimens, and treatment durations were employed, with durations of immunotherapy ranging from 1-16 cycles. Complete R0 resections were consistently achieved in 98%-100% of resections. Of patients who received neoadjuvant immunotherapy and underwent resection, 50%-91% had ypT0N0 pathology. The safety profiles were generally favorable, with Grade 1-2 treatment-related adverse events (mostly immune-related) during immunotherapy reported in 22.2%-70% of patients. Postoperative complications following neoadjuvant immunotherapy were reassuring, with no severe complications reported. LIMITATIONS: Small number of heterogeneous and uncontrolled studies precluding a meta-analysis. CONCLUSIONS: Neoadjuvant immune checkpoint inhibition is associated with high rates of pathologic complete responses in locally advanced colon cancer. The literature is limited, particularly for postoperative outcomes, and more studies are needed to understand the safety and positioning of these regimens in the neoadjuvant context.

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Neoadjuvant Immune Checkpoint Inhibition Improves Organ Preservation in T4bM0 Colorectal Cancer With Mismatch Repair Deficiency: A Retrospective Observational Study

Cited by 19 publications

References 27 publications

Clinicopathological characteristics of high microsatellite instability/mismatch repair-deficient colorectal cancer: A narrative review

Clinicopathological characteristics of high microsatellite instability/mismatch repair-deficient colorectal cancer: A narrative review

Neoadjuvant chemotherapy does not increase risk for anastomotic leak for simultaneous resection of primary colon cancer with synchronous liver metastasis: A NSQIP‐colectomy analysis

Systematic Review of Neoadjuvant Immunotherapy for Mismatch Repair Deficient Locally Advanced Colon Cancer: An Emerging Strategy

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