Complete pathological response in rectal cancer utilising novel treatment strategies for neo-adjuvant therapy: A systematic review

Wilson, Kasmira; Flood, Michael P.; Narasimhan, Vignesh; Pham, Toàn; Warrier, Satish; Ramsay, Robert G.; Michael, M; Heriot, Alexander G.

doi:10.1016/j.ejso.2021.03.245

Cited by 12 publications

(11 citation statements)

References 104 publications

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“…Histopathological examination showed that samples from the rectum were significantly smaller and showed higher levels of necrosis, possibly due to neoadjuvant therapy [ 26 ]. Survival analysis indicated that tumor budding assessment in CRC was significantly associated with survival, as previously described in the literature [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

PINK1 Immunoexpression Predicts Survival in Patients Undergoing Hepatic Resection for Colorectal Liver Metastases

Celis-Pinto

Fernández-Velasco

Corte-Torres

et al. 2023

IJMS

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PTEN-induced kinase-1 (PINK1) is the initiator of the canonical mitophagy pathway. Our aim was to study the immunoexpression of PINK1 in surgical specimens from ninety patients with metastatic colorectal adenocarcinoma (CRC) to the liver (CRLM). Tissue arrays were produced, and immunohistochemical studies were analyzed by the H-Score method. The mean immunoexpression of PINK1 in normal tissues was between 40 to 100 points. In tumoral tissues, positive PINK1 immunoexpression was observed in all samples, and no differences were noted between CRCs. In CRLMs, a significant under-expression was noted for PINK1 from the rectum (71.3 ± 30.8; p < 0.042) compared to other sites. Altered PINK1 immunoexpression in CRCs, either higher than 100 points or lower than 40 points, was associated with worse overall survival (OS) (p < 0.012) due to a shorter post-metastatic survival (PMS) (p < 0.023), and it was found to be a significant independent predictor of prognosis in a multivariate model for OS and PMS (HR = 1.972, 95% CI 0.971–4.005; p = 0.022. HR = 2.023, 95% CI 1.003–4.091; p = 0.037, respectively). In conclusion, altered PINK1 immunoexpression determined in CRCs with resected CRLM predicts a worse prognosis, possibly due to the abnormal function of mitophagy.

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Section: Discussionmentioning

confidence: 99%

PINK1 Immunoexpression Predicts Survival in Patients Undergoing Hepatic Resection for Colorectal Liver Metastases

Celis-Pinto

Fernández-Velasco

Corte-Torres

et al. 2023

IJMS

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“…According to previous reports, the pCR rate of RC patients at the time of surgery is in the range of only 8% to 20%. Up to 40% of RC patients are resistant to neoadjuvant chemoradiotherapy (nCRT), with some experiencing a progression of disease and others showing a slight regression to stable disease [3][4][5]. Clearly, different responses to nCRT contribute to varying clinical out-comes, including disease-free survival (DFS) and overall survival (OS) [2,3].…”

Section: Introductionmentioning

confidence: 99%

Biomarkers for Predicting the Response to Radiation-Based Neoadjuvant Therapy in Rectal Cancer

Chen¹,

Yang²,

Chen³

et al. 2022

Front. Biosci. (Landmark Ed)

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Locally advanced rectal cancer (RC) is treated with neoadjuvant chemoradiotherapy (nCRT) followed by radical surgery. Currently, organ-sparing approaches and/or "watch-and-wait" strategies other than unnecessary surgery have been suggested as the best option for patients who achieve complete regression after neoadjuvant treatment. However, patients respond differently to nCRT, hence the urgent need for effective methods to predict whether individual rectal cancer patients could benefit from this treatment. In this review, we summarize the biomarkers reported to be potential predictors of the therapeutic response of RC to nCRT. Biomarkers that are associated with genes, ribonucleic acid (RNA) and proteins are summarized and described first, followed by other types including immune and tumour microenvironment-related biomarkers, imaging biomarkers, microbiome-associated biomarkers, and blood-based biomarkers.

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“… 6 , 7 With the widespread implementation of NCRT as the standard of care, approximately 15–25% of patients who were treated with NCRT prior to surgery had no traces of neoplastic cells in the pathological specimen, a phenomenon widely known as pathological complete response (pCR). 8 , 9 This finding has led to the introduction of a new therapeutic strategy of watch and wait that omits surgery, with its significant implication on patients’ quality of life. It includes close clinical, radiological, and endoscopic follow-up in patients who achieve a complete response.…”

Section: Introductionmentioning

confidence: 99%

Total Neoadjuvant Therapy Is a Predictor for Complete Pathological Response in Patients Undergoing Surgery for Rectal Cancer

Horesh

Freund

Garoufalia

et al. 2022

Journal of Gastrointestinal Surgery

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Introduction Total neoadjuvant therapy (TNT) is a new therapeutic strategy in patients with rectal cancer. We examined the role of TNT, in addition to other pre-operative factors, as a predictor for pathologic complete response (pCR). Methods A retrospective analysis of all rectal cancer patients who underwent surgery between 2016 and 2021 was conducted. Patients were classified into two groups—pCR group and residual tumor group. Patient data were reviewed and entered into univariate and multivariate analyses to determine predictors of pCR. Results A total of 172 patients were treated with neoadjuvant therapy and underwent surgery during the study period. Sixty patients (34.9%) were treated with TNT while 112 (65.1%) were treated with traditional neoadjuvant chemoradiation. The overall pCR rate was 25.6% (44 patients), with 31.6% (19 patients) in patients who received TNT compared to 22.3% (25 patients) in patients who received neoadjuvant chemoradiation (NCRT). Univariate analysis of clinical and radiological factors correlated with pCR demonstrated no significant differences between the two groups in cT stage ( p = 0.46), cN stage ( p = 0.52), positive circumferential resection margin (CRM) ( p = 0.72), tumor location ( p = 0.35), symptomatic presentation ( p = 0.09), and anal sphincter involvement ( p = 0.68). Multivariate logistic analysis demonstrated that only pre-operative TNT (OR:2.35; 95% CI 1.06–5.25; p = 0.03) was predictive of pCR, while extramural vascular invasion (EMVI) was a predictor for lower rates of pCR (OR: 0.28; 95% CI 0.09–0.9; p = 0.03). Conclusion Rectal cancer patients undergoing TNT prior to surgery have a higher chance of developing a complete pathologic response. Evaluation of this therapy should be continued and extended to larger numbers of patients to see if the differences we observed are real.

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Complete pathological response in rectal cancer utilising novel treatment strategies for neo-adjuvant therapy: A systematic review

Cited by 12 publications

References 104 publications

PINK1 Immunoexpression Predicts Survival in Patients Undergoing Hepatic Resection for Colorectal Liver Metastases

PINK1 Immunoexpression Predicts Survival in Patients Undergoing Hepatic Resection for Colorectal Liver Metastases

Biomarkers for Predicting the Response to Radiation-Based Neoadjuvant Therapy in Rectal Cancer

Total Neoadjuvant Therapy Is a Predictor for Complete Pathological Response in Patients Undergoing Surgery for Rectal Cancer

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