T‐stage downstaging of locally advanced rectal cancer after neoadjuvant chemoradiotherapy is not associated with reduced recurrence after adjusting for tumour characteristics

Hayes, Ian; Milanzi, Elasma; Pelly, Rachel; Gibbs, Peter; Reece, Jeanette C.

doi:10.1002/jso.26932

Cited by 3 publications

(2 citation statements)

References 49 publications

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“…The study by Hayes et al showed similar results. [ 32 ] Their investigation on 528 rectal cancer patients showed that even in the absence of adverse prognostic factors, ypT downstaging was not associated with reduced tumor recurrence. [ 32 ] This is in accordance with our finding that the LARC patients were more than 2 times more likely to have a tumor relapse with the positive ypN status.…”

Section: Discussionmentioning

confidence: 99%

“…[ 32 ] Their investigation on 528 rectal cancer patients showed that even in the absence of adverse prognostic factors, ypT downstaging was not associated with reduced tumor recurrence. [ 32 ] This is in accordance with our finding that the LARC patients were more than 2 times more likely to have a tumor relapse with the positive ypN status. American joint comitee on cancer recommends harvesting a minimum of 12 lymph nodes in the surgical specimens to ensure the adequacy of surgery in CRC patients.…”

Section: Discussionmentioning

confidence: 99%

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Risk-factors for locally advanced rectal cancer relapse after neoadjuvant chemoradiotherapy: A single center experience

Stupar,

Jungić,

Gojković

et al. 2023

Medicine

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The overall prognosis of locally advanced rectal cancer (LARC) remains unsatisfactory due to a high incidence of disease relapse. The present understanding of the factors that determine the likelihood of recurrence is limited or ineffective. We aimed to identify the main risk factors influencing tumor relapse in LARC patients after neoadjuvant chemoradiotherapy (nCRT) and surgical treatment in a single center in Republika Srpska. Patients with stage II or stage III who received nCRT before surgery for primary rectal cancer at the Oncology Clinic, University Clinical Center of Republika Srpska from January 2017 and December 2022 were included in the study. We collected patient demographics, clinical stage and characteristics, neoadjuvant therapy, and surgical methods, along with the pathological response after treatment completion, and analyzed them to identify the risk factors for tumor relapse. Out of 109 patients diagnosed with LARC, 34 (31,2%) had tumor relapse. The median time to relapse was 54 months. Participants with clinical T4 stage had a significantly shorter relapse time compared to the patients with clinical T2/3 stage. Subjects with positive lymph nodes removed, perivascular and perineural invasion, intraoperative perforation and patients without ypN stage improvement had significantly shorter time to relapse. Subjects with T4 stage had more than 4 times higher risk of relapse than patients with clinical T2/3 stage. Higher clinical T stage was an essential risk factor for tumor relapse in LARC patients after nCRT and surgical treatment. Comprehensive understanding and identification of the risk factors for tumor relapse in LARC patients are crucial for improving their long-term outcomes.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Risk-factors for locally advanced rectal cancer relapse after neoadjuvant chemoradiotherapy: A single center experience

Stupar,

Jungić,

Gojković

et al. 2023

Medicine

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T‐stage downstaging of locally advanced rectal cancer after neoadjuvant chemoradiotherapy is not associated with reduced recurrence after adjusting for tumour characteristics

Hayes

Milanzi

Pelly

et al. 2022

Journal of Surgical Oncology

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Background and Objectives: Prior studies examining prognostic outcomes of locally advanced rectal adenocarcinomas achieving a complete pathological response following neoadjuvant chemoradiotherapy (nCRT) did not adjust for adverse prognostic factors in multivariate analyses and account for magnetic resonance imaging tumour staging inaccuracy pre-nCRT. We aimed to clarify prognostic outcomes in mT3 rectal adenocarcinomas with ypT-downstaging post-nCRT in robust adjusted analyses.Methods: Retrospective analysis of prospectively-collected clinical data from 528 mT3 rectal adenocarcinomas ≤12 cm from the anal verge, any N-stage, no metastases, post-nCRT following total mesorectal excision (TME). Recurrence outcomes (local and distant combined) of tumours with complete ypT-downstaging (ypT0) post-nCRT before TME compared with no ypT-downstaging (≥ypT3) were examined using multivariate Cox regression, adjusting for confounders and accounting for pre-nCRT mT3-staging inaccuracy using bootstrapping.Results: Complete ypT-downstaging was achieved in of 17.6% tumours and correlated strongly with complete pathological response. Complete ypTdownstaging was not associated with reduced recurrence hazards compared with no ypT-downstaging (hazard ratio = 0.60; 95% confidence interval [CI]: 0.23−1.56; p = 0.30). Lymphovascular invasion (LVI) and ypN+ve increased recurrence hazards by 1.8-fold (95% CI: 1.10−2.79; p = 0.02) and 2.3-fold (95% CI: 1.48−3.54; p = 0.0002), respectively. Conclusion:Complete ypT-downstaging was not associated with reduced recurrence after adjusting for confounders and accounting for mT3-staging inaccuracy, even in the absence of adverse prognostic factors (ypN+, LVI).

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Multi-dataset study on neoadjuvant treatment-related prognostic model and molecular network mechanism of locally advanced rectal cancer

Su,

Wu,

Xing

2024

Preprint

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Backgrounds Local advanced rectal cancer (LARC) is a common disease occurrence in clinical settings due to its unique anatomical location and treatment approach. The effectiveness of neoadjuvant chemoradiotherapy (nCRT) plays a crucial role in determining the appropriate treatment and prognosis for patients. Currently, there exists no universally acknowledged benchmark for prognosticating the effectiveness of neoadjuvant therapy. Our study obtained the GSE150082 dataset from the NCBI Geo Public Database, consisting of expression profile data for 39 groups of patients who either responded to nCRT or did not. Differential gene analysis was performed using the Limma package with a significance threshold of p < 0.05 and |log fold change| > 0.585. The functions and pathways associated with the differentially expressed genes were analyzed, and a protein interaction network was constructed using Cytoscape software. Additionally, the TCGA data was used to identify prognostic-related genes from the differential genes through Cox univariate regression and the lasso regression algorithm. Predictive models were then constructed and validated using both internal and external datasets. Results A total of 633 differentially expressed genes associated with nCRT were identified, comprising 238 up-regulated and 395 down-regulated genes. These genes are predominantly enriched in pathways related to innate immune response, regulation of biological stimulus-response, and cell activation. The results from gene screening and the construction of a predictive model demonstrate the model's efficacy in effectively distinguishing between high- and low-risk patients. This predictive capability was validated in both the training set and an external validation set. Additionally, an analysis of the relationship between the risk score and immune infiltration in the tumor microenvironment unveiled a potential molecular mechanism, suggesting that the risk score may impact patient prognosis by modulating specific immune cell populations and immune-related genes. Conclusions MCOLN3、CINP、HAND2 and CCDC85A might be the identified key genes and play a critical role in several pathways associated with response to nCRT. Furthermore, a risk score model was constructed based on prognosis-related genes, providing potential molecular markers and therapeutic targets for personalized strategies in nCRT. Our findings could potentially offer a fresh and innovative outlook for future treatment for patients with LARC.

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T‐stage downstaging of locally advanced rectal cancer after neoadjuvant chemoradiotherapy is not associated with reduced recurrence after adjusting for tumour characteristics

Cited by 3 publications

References 49 publications

Risk-factors for locally advanced rectal cancer relapse after neoadjuvant chemoradiotherapy: A single center experience

Risk-factors for locally advanced rectal cancer relapse after neoadjuvant chemoradiotherapy: A single center experience

T‐stage downstaging of locally advanced rectal cancer after neoadjuvant chemoradiotherapy is not associated with reduced recurrence after adjusting for tumour characteristics

Multi-dataset study on neoadjuvant treatment-related prognostic model and molecular network mechanism of locally advanced rectal cancer

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