Efficacy and Safety of Neoadjuvant Monoimmunotherapy With PD-1 Inhibitor for dMMR/MSI⁃H Locally Advanced Colorectal Cancer: A Single-Center Real-World Study

Zhang, Xuan; Yang, Renfang; Wu, Tao; Cai, Xinyi; Li, Guoyu; Yu, Kun; Li, Yong; Ding, Rong; Dong, Chao; Li, Jinsha; Hu, Ruixi; Qian, Feng; Li, Yunfeng

doi:10.3389/fimmu.2022.913483

Cited by 25 publications

(27 citation statements)

References 37 publications

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“…[20] Immunotherapy has also shown some preliminary results in neoadjuvant treatment for locally advanced rectal cancer. [31][32][33][34] As research progresses, individualized treatment plans need to be developed for specific patients.…”

Section: Discussionmentioning

confidence: 99%

Neoadjuvant chemoradiotherapy with capecitabine based regimen in locally advanced rectal cancer: A retrospective study

Li,

Zhang,

et al. 2023

Medicine

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Capecitabine-based neoadjuvant chemoradiotherapy (nCRT) is the standard treatment for locally advanced rectal cancer. The objective of this study is to analyze overall survival (OS), disease-free survival (DFS) and prognostic factors of patients with stage II to III rectal cancer treated with nCRT in our institution. Between March 2014 to June 2020, 121 locally advanced rectal cancer patients were retrospectively reviewed and analyzed. All of the enrolled patients were treated with capecitabine-based nCRT (pelvic radiotherapy: 45–50.4 Gy, 1.8 Gy/d plus concomitant capecitabine-based chemotherapy), total mesorectal excision surgery (surgery was carried out 8–12 weeks after the end of CRT), and capecitabine-based adjuvant chemotherapy. We examined the pathological complete response rate, 3-year OS, 3-year DFS and the other prognostic factors. Kaplan–Meier method and Log-rank test were used to estimate and compare survival rate. With a median follow-up of 36 months, 3-year DFS and 3-year OS was 74.4% and 83.2%, respectively. Among the 121 patients, 24 achieved pathological complete remission (19.8%). After multivariate analysis, ypTNM stage (TNM stage after neoadjuvant therapy) was significantly associated with DFS. Positive mesorectal fasciae (MRF) status on magnetic resonance imaging and ypTNM stage were significantly related to OS. CRT with capecitabine based regimen provides high rates of survival and sphincter preservation with acceptable toxicity. YpTNM stage was significantly associated with DFS; magnetic resonance imaging MRF status and ypTNM stage were significant factors for OS after multivariate analysis. Distant metastasis is the dominant mode of treatment failure, and it is crucial to optimize systemic treatment for newly diagnosed patients.

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Section: Discussionmentioning

confidence: 99%

Neoadjuvant chemoradiotherapy with capecitabine based regimen in locally advanced rectal cancer: A retrospective study

Li,

Zhang,

et al. 2023

Medicine

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“…Recent studies have suggested favorable pathological outcomes following neoadjuvant chemoradiotherapy plus targeted therapy ( 31 , 32 ). Immunotherapies, such as programmed cell death-1 or programmed cell death-ligand 1 inhibitors, also demonstrate encouraging clinical benefits including response rate, and the immune checkpoint represent a useful target to enhance tumor regression ( 33 , 34 ). Further investigation in a large cohort study is needed to improve prognosis in patients who are resistant to TNT.…”

Section: Discussionmentioning

confidence: 99%

Active surveillance in long period of total neoadjuvant therapy in rectal cancer: Early prediction of poor regression response

Zhang

Cao

et al. 2022

Front. Oncol.

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AimTo analyze locally advanced rectal cancer (LARC) patients and tumor characteristics during the period of total neoadjuvant therapy (TNT) and explore the risk factors that may predict poor tumor regression in response to TNT.Materials and methodsThe data of 120 LARC patients who received TNT from December 2016 and September 2019 in our hospital were retrospectively analyzed. The clinicopathological characteristics of patients with different tumor regression responses were compared. Then we divided patients into two groups according to the carcinoembryonic antigen (CEA) clearance pattern after chemoradiation to explore risk factors that might predict the tumor regression response.ResultsOf 120 LARC patients, 34 (28.3%) exhibited poor regression. Stratified analysis by tumor response showed that patients with poor response to TNT were more likely to obtain elevated CEA during the course of TNT (all P < 0.05). For those with elevated pretreatment CEA, fewer patients with poor response obtained normal CEA after chemoradiation (13.6% vs. 72.7%, P < 0.001). Besides, less patients’ CEA levels in the poor response group decreased by greater than 50% after chemoradiation when compared with that in the good response group (18.2% vs. 60.6%, P = 0.002). Stratified analysis by CEA clearance pattern after chemoradiation showed patients who obtained an elevated pretreatment CEA and decreased by less than 50% after chemoradiation were more likely to have poor response to TNT compared to others (76.2% vs. 18.2%, P < 0.001). Logistic multivariate analysis revealed that cN2 (95% CI 1.553-16.448), larger tumors (95% CI 2.250-21.428) and CEA clearance pattern after chemoradiation (95% CI 1.062-66.992) were independent risk factors for poor tumor regression response.ConclusionApproximately one-fourth of LARC patients with TNT achieved a poor regression response. Here, cN2, larger tumor size before treatment and elevated CEA levels were considered predictive features of a poor response. Active surveillance of CEA levels during the TNT course are potentially important, and CEA levels after chemoradiation might have important implications for the tumor response to TNT.

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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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Efficacy and Safety of Neoadjuvant Monoimmunotherapy With PD-1 Inhibitor for dMMR/MSI⁃H Locally Advanced Colorectal Cancer: A Single-Center Real-World Study

Cited by 25 publications

References 37 publications

Neoadjuvant chemoradiotherapy with capecitabine based regimen in locally advanced rectal cancer: A retrospective study

Neoadjuvant chemoradiotherapy with capecitabine based regimen in locally advanced rectal cancer: A retrospective study

Active surveillance in long period of total neoadjuvant therapy in rectal cancer: Early prediction of poor regression response

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

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