scholarly journals Genomic and Transcriptomic Characterisation of Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1808
Author(s):  
Sinead Toomey ◽  
Jillian Gunther ◽  
Aoife Carr ◽  
David C. Weksberg ◽  
Valentina Thomas ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiotherapy ◽  
Advanced Rectal Cancer ◽  
Preliminary Evidence ◽  
Locally Advanced Rectal Cancer ◽  
Poor Responders ◽  
Repair Deficiency ◽  
Whole Exome ◽  
Pre Treatment

Standard treatment for locally advanced rectal cancer (LARC) is neoadjuvant chemoradiotherapy (NACRT), followed by surgical resection. However, >70% of patients do not achieve a complete pathological response and have higher rates of relapse and death. There are no validated pre- or on-treatment factors that predict response to NACRT besides tumour stage and size. We characterised the response of 33 LARC patients to NACRT, collected tumour samples from patients prior to, during and after NACRT, and performed whole exome, transcriptome and high-depth targeted sequencing. The pre-treatment LARC genome was not predictive of response to NACRT. However, in line with the increasing recognition of microbial influence in cancer, RNA analysis of pre-treatment tumours suggested a greater abundance of Fusobacteria in intermediate and poor responders. In addition, we investigated tumour heterogeneity and evolution in response to NACRT. While matched pre-treatment, on-treatment and post-treatment tumours revealed minimal genome evolution overall, we identified cases in which microsatellite instability developed or was selected for during NACRT. Recent research has suggested a role for adaptive mutability to targeted therapy in colorectal cancer cells. We provide preliminary evidence of selection for mismatch repair deficiency in response to NACRT. Furthermore, pre-NACRT genomic landscapes do not predict treatment response but pre-NACRT microbiome characteristics may be informative.

scholarly journals Pre-Treatment T2-WI Based Radiomics Features for Prediction of Locally Advanced Rectal Cancer Non-Response to Neoadjuvant Chemoradiotherapy: A Preliminary Study

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1894 ◽  
Author(s):  
Bianca Petresc ◽  
Andrei Lebovici ◽  
Cosmin Caraiani ◽  
Diana Sorina Feier ◽  
Florin Graur ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Tumor Regression ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Neoadjuvant Chemoradiotherapy ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Imaging Biomarkers ◽  
Tumor Regression Grade ◽  
Pre Treatment

Locally advanced rectal cancer (LARC) response to neoadjuvant chemoradiotherapy (nCRT) is very heterogeneous and up to 30% of patients are considered non-responders, presenting no tumor regression after nCRT. This study aimed to determine the ability of pre-treatment T2-weighted based radiomics features to predict LARC non-responders. A total of 67 LARC patients who underwent a pre-treatment MRI followed by nCRT and total mesorectal excision were assigned into training (n = 44) and validation (n = 23) groups. In both datasets, the patients were categorized according to the Ryan tumor regression grade (TRG) system into non-responders (TRG = 3) and responders (TRG 1 and 2). We extracted 960 radiomic features/patient from pre-treatment T2-weighted images. After a three-step feature selection process, including LASSO regression analysis, we built a radiomics score with seven radiomics features. This score was significantly higher among non-responders in both training and validation sets (p < 0.001 and p = 0.03) and it showed good predictive performance for LARC non-response, achieving an area under the curve (AUC) = 0.94 (95% CI: 0.82–0.99) in the training set and AUC = 0.80 (95% CI: 0.58–0.94) in the validation group. The multivariate analysis identified the radiomics score as an independent predictor for the tumor non-response (OR = 6.52, 95% CI: 1.87–22.72). Our results indicate that MRI radiomics features could be considered as potential imaging biomarkers for early prediction of LARC non-response to neoadjuvant treatment.

scholarly journals Carcinoembryonic antigen BEFORE AND AFTER neoadjuvant chemoradiotherapy IN PREDICTION OF pathological complete response in patients with locally advanced rectal cancer

2018 ◽  
Vol 17 (5) ◽  
pp. 60-66
Author(s):  
N. V. Severskaya ◽  
D. V. Erygin ◽  
Yu. V. Aleksandrov ◽  
N. G. Minaeva ◽  
N. Yu. Dvinskikh ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Pathological Complete Response ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiotherapy ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Before And After ◽  
Pre Treatment ◽  
Well Differentiated

Carcinoembryonic antigen (CEA) is widely used to evaluate the effectiveness of treatment in patients with rectal cancer.The aim of the studywas to investigate whether the CEA levels measured before and after neoadjuvant chemoradiotherapy (nCRT) can be used to predict pathological complete response (pCR) in patients with locally advanced rectal cancer.Material and methods.179 patients with locally advanced rectal cancer were treated with nCRT followed by surgical treatment. The serum CEA level was measured before and 610 weeks after the completion of nCRT. Preand post nCRT CEA levels were compared with pCR. The factors associated with pCR were studied.Results.pCR after nCRT was achieved in 12 % (22/179) patients. The incidence of pCR was higher in patients with normal (<5 ng/mL) pre-treatment CEA level (20 %vs8 %, p=0.019). In patients with the elevated pre-treatment CEA level (> 5 ng/mL), there were no significant differences in the incidence of pCR between cases with normalization and without normalization of CEA level after treatment (p=0.08). The maximum likelihood of pCR determined by the ROC curve was <2.8 ng/mL with pre-treatment CEA (31 %) and <1.8 ng/mL with post-treatment CEA (23 %). Well differentiated tumors (G1) had higher likelihood of pCR (46%) in patients with low pre-treatment CEA (<2.8 ng/mL).Conclusion.Low CEA before and after nCRT is a predictor of pCR. Well differentiated tumors increase the probability of pCR after nCRT.

scholarly journals A panel of tumor biomarkers to predict complete pathological response to neo-adjuvant treatment in Locally Advanced Rectal Cancer

2021 ◽  
Author(s):  
Chiara Dalle Fratte ◽  
Silvia Mezzalira ◽  
Jerry Polesel ◽  
Elena De Mattia ◽  
Antonio Palumbo ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Cancer Patients ◽  
Pathological Complete Response ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiotherapy ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Classification And Regression Tree ◽  
Pre Treatment

Pathological complete response after neoadjuvant chemoradiotherapy in locally advanced rectal cancer patients is related to a favorable prognosis. The identification of early biomarkers predictive of pathological complete response would help to optimize the multimodality management of the patients. A panel of 11 tumor-related proteins was investigated by immunohistochemistry in the pre-treatment biopsy of a group of locally advanced rectal cancer patients, to identify early biomarkers of pathological complete response to neoadjuvant chemoradiotherapy. A mono-institutional retrospective cohort of 95 stage II/III locally advanced rectal cancer patients treated with neoadjuvant chemoradiotherapy and surgery was selected based on clinical-pathological characteristics and the availability of a pre-treatment tumor biopsy. Eleven selected protein markers expression (MLH1, GLUT1, Ki67, CA-IX, CXCR4, COX2, CXCL12, HIF1, VEGF, CD44, and RAD51) was investigated. The optimal cut-off values were calculated by receiver operating characteristic curve analysis. Classification and regression tree analysis was performed to investigate the biomarkers interaction. Patients presenting either Ki67, HIF1 or RAD51 below the cut-off value, or CXCR4 or COX2 above the cut-off value, were more likely to get a pathological complete response. Classification and regression tree analysis identified three groups of patients resulting from the combination of Ki67 and CXCR4 expression. Patients with high expression of Ki67 had the lowest chance to get a pathological complete response (18%), as compared to patients with low expression of both Ki67 and CXCR4 (29%), and patients with low Ki67 and high CXCR4 expression (70%). Pre-treatment Ki67, CXCR4, COX2, HIF1, RAD51 in tumor biopsies are associated with pathological complete response after neoadjuvant chemoradiotherapy in locally advanced rectal cancer. A combined evaluation of Ki67 and CXCR4 would increase their predictive potential. If validated, their optimal cut-off could be used to select patients for a tailored multi-modality treatment.

Adjuvant chemotherapy following neoadjuvant chemoradiotherapy and surgery for locally advanced rectal cancer.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 626-626
Author(s):  
Kirsten Elizabeth Jean Laws ◽  
Christina Wilson ◽  
David McIntosh ◽  
Stephen Harrow
Keyword(s):  
Decision Making ◽  
Rectal Cancer ◽  
Adjuvant Chemotherapy ◽  
Adjuvant Treatment ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiotherapy ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Number Of Patients ◽  
Pre Treatment

626 Background: Established guidelines exist for indications of adjuvant chemotherapy in colon cancer. However, in patients receiving neoadjuvant chemoradiotherapy for locally advanced rectal cancer, the benefit of adjuvant chemotherapy remains unproven. We evaluated clinical decision making behind adjuvant chemotherapy for locally advanced rectal cancer patients in our institute. Methods: Patients treated with long course chemoradiotherapy between January 2008 and December 2009 were identified. Exclusion criteria were inoperable disease, postoperative, recurrence, or palliative intent. 231 cases were examined retrospectively for the decisions behind giving or withholding adjuvant chemotherapy. Results: 35 (15%) were ineligible for consideration of adjuvant chemotherapy due to disease progression. 38 patients (16.4%) received chemotherapy in the adjuvant setting and 158 patients (68.4%) were potentially eligible for adjuvant chemotherapy, but did not receive it. The majority of clinicians based their decisions on post operative pathology results, and the key factor in decision making was final pathological stage in 65%. Clinicians considered pre-treatment imaging a key factor in only 14% of cases, despite a considerable number of patients being downstaged from a potentially higher initial pre-treatment stage that could have warranted adjuvant treatment. A considerable number of patients (25%) were deemed unfit for adjuvant treatment following neoadjuvant chemoradiotherapy and surgery due to toxicity of combined treatment. Conclusions: This analysis highlights the difficulty in clinical decision making for adjuvant chemotherapy in rectal cancer. The accuracy of pre-treatment staging is difficult to ascertain and its use to justify post operative treatment uncertain. It appears the majority of clinicians in our institute base their decision on post operative pathology. A considerable number of patients were not fit for consideration of adjuvant treatment due to toxicity of previous treatment. Further research is warranted as to the benefits of adjuvant chemotherapy, particularly in a setting where prior treatment already causes significant toxicity.

scholarly journals Molecular and Dynamic Evaluation of Proteins Related to Resistance to Neoadjuvant Treatment with Chemoradiotherapy in Circulating Tumor Cells of Patients with Locally Advanced Rectal Cancer

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1539
Author(s):  
Virgílio Souza e Silva ◽  
Emne Ali Abdallah ◽  
Bianca de Cássia Troncarelli Flores ◽  
Alexcia Camila Braun ◽  
Daniela de Jesus Ferreira Costa ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Transforming Growth Factor ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Neoadjuvant Chemoradiotherapy ◽  
Disease Free Survival ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer

The heterogeneity of response to neoadjuvant chemoradiotherapy (NCRT) is still a challenge in locally advanced rectal cancer (LARC). The evaluation of thymidylate synthase (TYMS) and RAD23 homolog B (RAD23B) expression in circulating tumor cells (CTCs) provides complementary clinical information. CTCs were prospectively evaluated in 166 blood samples (63 patients) with LARC undergoing NCRT. The primary objective was to verify if the absence of RAD23B/TYMS in CTCs would correlate with pathological complete response (pCR). Secondary objectives were to correlate CTC kinetics before (C1)/after NCRT (C2), in addition to the expression of transforming growth factor-β receptor I (TGF-βRI) with survival rates. CTCs were isolated by ISET and evaluated by immunocytochemistry (protein expression). At C1, RAD23B was detected in 54.1% of patients with no pCR and its absence in 91.7% of patients with pCR (p = 0.014); TYMS− was observed in 90% of patients with pCR and TYMS+ in 51.7% without pCR (p = 0.057). Patients with CTC2 > CTC1 had worse disease-free survival (DFS) (p = 0.00025) and overall survival (OS) (p = 0.0036) compared with those with CTC2 ≤ CTC1. TGF-βRI expression in any time correlated with worse DFS (p = 0.059). To conclude, RAD23B/TYMS and CTC kinetics may facilitate the personalized treatment of LARC.

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