Predictors for complete pathological response for stage II and III rectal cancer following neoadjuvant therapy - A systematic review and meta-analysis

Huang, Yeqian; Lee, Daniel; Young, Christopher J.

doi:10.1016/j.amjsurg.2020.01.001

Cited by 28 publications

(16 citation statements)

References 29 publications

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“…When the median size (5 cm) was used as cut-off, an association with CR was seen only among patients receiving scRT+CT. The results confirm the clinical impression that even tumors larger than 5 cm can respond completely, with increasing proportions CR with more intensive treatment, but that smaller tumors reach CR more often [39]. In the study by Garland et al including 294 patients, size was predictive (p = 0.008), but no cut-off was defined [13].…”

Section: Discussionsupporting

confidence: 76%

A Comprehensive Evaluation of Associations Between Routinely Collected Staging Information and The Response to (Chemo)Radiotherapy in Rectal Cancer

Hammarström

Imam

Mezheyeuski

et al. 2020

Cancers

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Radiotherapy (RT) or chemoradiotherapy (CRT) are frequently used in rectal cancer, sometimes resulting in complete tumor remission (CR). The predictive capacity of all clinical factors, laboratory values and magnetic resonance imaging parameters performed in routine staging was evaluated to understand what determines an excellent response to RT/CRT. A population-based cohort of 383 patients treated with short-course RT (5 × 5 Gy in one week, scRT), CRT, or scRT with chemotherapy (scRT+CT) and having either had a delay to surgery or been entered into a watch-and-wait program were included. Complete staging according to guidelines was performed and associations between investigated variables and CR rates were analyzed in univariate and multivariate analyses. In total, 17% achieved pathological or clinical CR, more often after scRT+CT and CRT than after scRT (27%, 18% and 8%, respectively, p < 0.001). Factors independently associated with CR included clinical tumor stage, small tumor size (<3 cm), tumor level, and low CEA-value (<3.8 μg/L). Size or stage of the rectal tumor were associated with excellent response in all therapy groups, with small or early stage tumors being significantly more likely to reach CR (p = 0.01 (scRT), p = 0.01 (CRT) and p = 0.02 (scRT+CT). Elevated level of carcinoembryonic antigen (CEA) halved the chance of response. Extramural vascular invasion (EMVI) and mucinous character may indicate less response to RT alone.

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Section: Discussionsupporting

confidence: 76%

A Comprehensive Evaluation of Associations Between Routinely Collected Staging Information and The Response to (Chemo)Radiotherapy in Rectal Cancer

Hammarström

Imam

Mezheyeuski

et al. 2020

Cancers

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“…None of the other factors we investigated showed a similar correlation with pCR. Tumor size, 25 clinical T and N stage, 26 tumor grade, 27 circumferential involvement, and tumor shape 28 were all equivocal in patients who achieved pCR and those who did not, despite previous descriptions in the literature regarding their possible predictive role for pCR. However, it is plausible that a small sample size did not allow enough power to detect significant associations between these factors and pCR.…”

Section: Discussionmentioning

confidence: 81%

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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“…Diverse clinical, radiological, pathological, and molecular factors have been associated to LARC treatment efficacy. Whereas all these contribute to the understanding of the biology of therapeutic response, we still have no markers reaching the precision required for clinical applications, when responsive patients identified prior to cancer treatment would benefit from the adoption of non-operative therapies (“watch and wait”) ( 3 , 47 ) and refractory subjects could be spared from the conventional nCRT treatment. Despite the continuous search for histological, serological, cellular, and molecular markers, there are no established predictive factors to the response to nCRT in rectal cancer ( 48 ).…”

Section: Discussionmentioning

confidence: 99%

Exome and Tissue-Associated Microbiota as Predictive Markers of Response to Neoadjuvant Treatment in Locally Advanced Rectal Cancer

et al. 2022

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The clinical and pathological responses to multimodal neoadjuvant therapy in locally advanced rectal cancers (LARCs) remain unpredictable, and robust biomarkers are still lacking. Recent studies have shown that tumors present somatic molecular alterations related to better treatment response, and it is also clear that tumor-associated bacteria are modulators of chemotherapy and immunotherapy efficacy, therefore having implications for long-term survivorship and a good potential as the biomarkers of outcome. Here, we performed whole exome sequencing and 16S ribosomal RNA (rRNA) amplicon sequencing from 44 pre-treatment LARC biopsies from Argentinian and Brazilian patients, treated with neoadjuvant chemoradiotherapy or total neoadjuvant treatment, searching for predictive biomarkers of response (responders, n = 17; non-responders, n = 27). In general, the somatic landscape of LARC was not capable to predict a response; however, a significant enrichment in mutational signature SBS5 was observed in non-responders (p = 0.0021), as well as the co-occurrence of APC and FAT4 mutations (p < 0.05). Microbiota studies revealed a similar alpha and beta diversity of bacteria between response groups. Yet, the linear discriminant analysis (LDA) of effect size indicated an enrichment of Hungatella, Flavonifractor, and Methanosphaera (LDA score ≥3) in the pre-treatment biopsies of responders, while non-responders had a higher abundance of Enhydrobacter, Paraprevotella (LDA score ≥3) and Finegoldia (LDA score ≥4). Altogether, the evaluation of these biomarkers in pre-treatment biopsies could eventually predict a neoadjuvant treatment response, while in post-treatment samples, it could help in guiding non-operative treatment strategies.

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Predictors for complete pathological response for stage II and III rectal cancer following neoadjuvant therapy - A systematic review and meta-analysis

Cited by 28 publications

References 29 publications

A Comprehensive Evaluation of Associations Between Routinely Collected Staging Information and The Response to (Chemo)Radiotherapy in Rectal Cancer

A Comprehensive Evaluation of Associations Between Routinely Collected Staging Information and The Response to (Chemo)Radiotherapy in Rectal Cancer

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

Exome and Tissue-Associated Microbiota as Predictive Markers of Response to Neoadjuvant Treatment in Locally Advanced Rectal Cancer

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