A prospective clinical study assessing the presence of exfoliated cancer cells and rectal washout including tumors in patients who receive neoadjuvant chemoradiotherapy for rectal cancer

Abstract Purpose:To investigate the prognostic effects of baseline volumetric PET/CT parameters including the maximum standard uptake value(SUVmax), metabolic tumor volume(MTV), and tumor lesion glycolysis(TLG) on treatment response and prognosis in locally-advanced rectal cancer(LARC) treated with neoadjuvant chemoradiotherapy(NACRT).Methods:Between 2015 and 2018, 51 patients with LARC treated with NACRT followed by surgery were included in this retrospective study. Patients were divided into 2 groups by tumor regression grade(TRG) as follows;Group I=TRG 1(No detectable cancer cells)+TRG 2(single cells and/or small groups of cancer cells) and Group II=TRG3(residual tumor outgrown by fibrosis)+TRG 4(remarkable fibrosis outgrown by tumor cells)+TRG 5(No fibrosis with extensive residual cancer).Results:Of the 51 patients, 34(66.7%) were male. The median age was 55(range,37-78) years. According to TRG status, 14(27.4%) patients were in group I and 37(72.6%) patients were in group II. The area under the curve(95% CI) was 0.749(0.593-0.905) in the ROC curve plotted for MTV. The cut of value for MTV was 12, with 70% sensitivity and 65% specificity. MTV was≥12 in 32(62.8%) patients. MTV and TLG values were significantly different between Group I and II, whereas there was no significant difference between the groups in terms of SUVmax values (p=0.006, p=0.033, and p=0.673, respectively). The disease-free survival was not reached in patients with MTV<12 vs. 20 months in those with MTV≥12 (p=0.323). In multivariate analysis, MTV(OR, 95% Cl, 5.00[1.17-21.383]) was found to be the factor that affected pathological complete response.Conclusion:In LARC treated with NACRT, MTV prior to treatment can help predict the response to treatment.

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Screening of MicroRNA Related to Irradiation Response and the Regulation Mechanism of miRNA-96-5p in Rectal Cancer Cells

Frontiers in Oncology ◽

10.3389/fonc.2021.699475 ◽

2021 ◽

Vol 11 ◽

Author(s):

Fengpeng Wu ◽

Bingyue Wu ◽

Xiaoxiao Zhang ◽

Congrong Yang ◽

Chaoxi Zhou ◽

...

Keyword(s):

Rectal Cancer ◽

Cancer Cells ◽

Locally Advanced ◽

Neoadjuvant Chemoradiotherapy ◽

Signal Transduction Pathway ◽

Advanced Rectal Cancer ◽

Locally Advanced Rectal Cancer ◽

Regulation Mechanism ◽

Canonical Wnt ◽

Irradiation Resistance

Neoadjuvant chemoradiotherapy has been widely used in the treatment of locally advanced rectal cancer due to the excellent advantages of irradiation in cancer therapy. Unfortunately, not every patient can benefit from this treatment, therefore, it is of great significance to explore biomarkers that can predict irradiation sensitivity. In this study, we screened microRNAs (miRNAs) which were positively correlated with irradiation resistance and found that miRNA-552 and miRNA-183 families were positively correlated with the irradiation resistance of rectal cancer, and found that high expression of miRNA-96-5p enhanced the irradiation resistance of rectal cancer cells through direct regulation of the GPC3 gene and abnormal activation of the canonical Wnt signal transduction pathway. Based on the radioreactivity results of patient-derived xenograft models, this is the first screening report for radio-resistant biomarkers in rectal cancer. Our results suggest that miRNA-96-5p expression is an important factor affecting the radiation response of colorectal cancer cells.

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SU-F-R-48: Early Prediction of Pathological Response of Locally Advanced Rectal Cancer Using Perfusion CT:A Prospective Clinical Study

Medical Physics ◽

10.1118/1.4955819 ◽

2016 ◽

Vol 43 (6Part7) ◽

pp. 3384-3384 ◽

Cited By ~ 1

Author(s):

K Nie ◽

L Shi ◽

N Yue ◽

S Jabbour ◽

S Kim ◽

...

Keyword(s):

Rectal Cancer ◽

Clinical Study ◽

Locally Advanced ◽

Advanced Rectal Cancer ◽

Locally Advanced Rectal Cancer ◽

Pathological Response ◽

Prospective Clinical Study ◽

Early Prediction

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O11: MYOFERLIN: A NOVEL BIOMARKER OF RADIOSENSITIVITY IN LOCALLY ADVANCED RECTAL CANCER

British Journal of Surgery ◽

10.1093/bjs/znab117.011 ◽

2021 ◽

Vol 108 (Supplement_1) ◽

Author(s):

H Fowler ◽

P Sutton ◽

D Bowden ◽

J Parsons ◽

D Vimalachandran

Keyword(s):

Colorectal Cancer ◽

Rectal Cancer ◽

Cancer Cells ◽

Locally Advanced ◽

Neoadjuvant Chemoradiotherapy ◽

Advanced Rectal Cancer ◽

Locally Advanced Rectal Cancer ◽

Radiation Doses ◽

Clonogenic Assays ◽

Colorectal Cancer Cells

Abstract Introduction Our proteomic data has validated that high levels of the protein myoferlin confers poorer response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer. Myoferlin plays a role in membrane repair and VEGF signal transduction, and is associated with worse prognosis in numerous other epithelial cancers. We aim to assess the impact of myoferlin on the radiosensitivity of rectal cancer. Method Clonogenic assays were performed using immortalised colorectal cancer cells (HCT116,HT29,LIM,MDST8) to assess survival at escalating radiation doses following knockdown with myoferlin siRNA or a small molecular inhibitor(WJ460). 3D models (spheroids) were used to examine the effect of WJ460 on tumour growth. Result Quantification of myoferlin using immunoblotting demonstrated that MDST8 and LIM were higher expressors than HCT116 and HT29. Higher levels correlated with increasing radio-resistance as calculated by colony formation efficiency (CFE). Using clonogenic assays, cells treated with myoferlin siRNA or WJ460 demonstrated increased radiosensitivity compared to controls across all radiation doses, most significantly at 4Gy. Treatment of spheroids with WJ460 significantly reduced growth compared to controls at all radiation doses (p<0.05), with WJ460 limiting growth considerably more than treatment with the current gold standard 5-FU. HCT116 spheroid volume day 15; WJ460 4.96um3,5-FU 6.74um3,DMSO 24.9um3. Conclusion Inhibition of myoferlin is associated with increased radiosensitivity of colorectal cancer cells, and treatment with a small molecular inhibitor significantly reduces growth in spheroid models. Further work is required further validate its potential use as a biomarker in locally advanced rectal cancer. Take-home message We have found that myoferlin is a protein associated with poor response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer. Manipulation of this protein sensitises the cancer cells to radiotherapy.

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