Dataset Information

Biomarker-based treatment selection in early-stage rectal cancer to promote organ preservation.

ABSTRACT:

Background

Total mesorectal excision (TME) remains commonplace for T1-2 rectal cancer owing to fear of undertreating a small proportion of patients with node-positive disease. Molecular stratification may predict cancer progression. It could be used to select patients for organ-preserving surgery if specific biomarkers were validated.

Methods

Gene methylation was quantified using bisulphite pyrosequencing in 133 unirradiated rectal cancer TME specimens. KRAS mutation and microsatellite instability status were also defined. Molecular parameters were correlated with histopathological indices of disease progression. Predictive models for nodal metastasis, lymphovascular invasion (LVI) and distant metastasis were constructed using a multilevel reverse logistic regression model.

Results

Methylation of the retinoic acid receptor ? gene, RARB, and that of the checkpoint with forkhead and ring finger gene, CHFR, was associated with tumour stage (RARB: 51·9 per cent for T1-2 versus 33·9 per cent for T3-4, P?ConclusionThis methylation biomarker panel provides a step towards accurate discrimination of indolent and aggressive rectal cancer subtypes. This could offer an improvement over the current standard of care, whereby fit patients are offered radical surgery.

SUBMITTER: Leong KJ

PROVIDER: S-EPMC4282074 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

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Publications

Biomarker-based treatment selection in early-stage rectal cancer to promote organ preservation.

Leong K J KJ Beggs A A James J J Morton D G DG Matthews G M GM Bach S P SP

The British journal of surgery 20140723 10

<h4>Background</h4>Total mesorectal excision (TME) remains commonplace for T1-2 rectal cancer owing to fear of undertreating a small proportion of patients with node-positive disease. Molecular stratification may predict cancer progression. It could be used to select patients for organ-preserving surgery if specific biomarkers were validated.<h4>Methods</h4>Gene methylation was quantified using bisulphite pyrosequencing in 133 unirradiated rectal cancer TME specimens. KRAS mutation and microsate ...[more]

PMID: 25052224

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Project description:BACKGROUND:Transanal minimally invasive surgery (TAMIS) is deployed for organ preservation in early rectal cancer and significant rectal polyps. Rapid evaporative ionisation mass spectrometry (REIMS) provides biochemical tissue analysis, which could be applied intraoperatively to give real-time tissue feedback to the surgeon and decrease the risk of an involved margin. However, the accuracy and feasibility of this approach have not been established. METHODS:In this prospective observational study, patients undergoing resection of rectal adenomas or carcinomas were recruited. An electrosurgical handpiece analysed tissues ex vivo using diathermy, with the aerosol aspirated into a Xevo G2-S ToF mass spectrometer. The relative abundance of lipids underwent predictive statistical modelling and leave-one-patient-out cross-validation. The outcomes of interest were the ability of REIMS to differentiate normal, adenomatous and cancerous tissue, or any disease subtype from normal. REIMS was coupled with TAMIS for in vivo sampling, assessing the accuracy of tissue recognition and distinguishing bowel wall layers. RESULTS:Forty-seven patients were included, yielding 266 spectra (121 normal, 109 tumour and 36 adenoma). REIMS differentiates normal, adenomatous and cancerous rectal tissues with 86.8% accuracy, and normal and adenomatous tissue with 92.4% accuracy and 91.4% accuracy when differentiating disease from normal. We have performed the first five in-man mass spectrometry augmented TAMIS (MS-TAMIS). In real time, MS-TAMIS can differentiate rectal mucosa and submucosa based on their relative abundance of triglycerides and glycerophospholipids. The ex vivo accuracy distinguishing diseased and normal tissues is maintained in vivo at 90%, with negative predictive value of 95%. The system identified a deep and lateral involved tumour margin during TAMIS. CONCLUSIONS:REIMS distinguishes rectal tissue types based on underlying lipid biology, and this can be translated in vivo by coupling it to TAMIS. There is a role for this technology in improving the efficacy of resection of early rectal cancers.

Project description:Non-operative management of rectal cancer is increasingly being used in selected patients. Most reports include patients treated with chemoradiotherapy (CRT) before inclusion into a Watch & Wait (W&W) programme. The aim of this study was to report outcomes from a single-centre W&W programme involving a large cohort of patients. Patients treated with chemoradiotherapy (CRT) or short-course radiotherapy (SCRT) with or without chemotherapy, between 2008 and 2020, who showed signs of a clinical complete response (cCR) were reviewed. Patients were assessed using digital rectal examination, flexible endoscopy, carcinoembryonic antigen measurement, MRI, and CT imaging, discussed at the multidisciplinary tumour board meeting, and followed up in a dedicated W&W programme as from 2015. Outcomes including regrowth and 3-year survival (time to regrowth or death) were prospectively evaluated. Of 142 patients who were assessed, 88 fulfilled the criteria for cCR. Treatment before cCR included CRT, SCRT with chemotherapy, and SCRT alone in 16 (18 per cent), 28 (32 per cent), and 44 (50 per cent) patients, respectively. Patients treated with CRT and SCRT with chemotherapy had more advanced clinical T- and N-stage, compared with patients treated with SCRT alone (clinical T-stage > 2: 81 per cent and 89 per cent versus 47 per cent, respectively; clinical N-stage > 0: 75 per cent and 93 per cent versus 68 per cent, respectively). Overall rate of regrowth was 19 per cent, with 31 per cent, 21 per cent, and 14 per cent following CRT, SCRT with chemotherapy, and SCRT alone, respectively. Uni- and multivariable analyses evaluating the clinical parameters revealed no statistically significant associations with risk of local regrowth. All but one patient with regrowth underwent salvage surgery. The 3-year survival rate (death with regrowth as competing risk) was 93 per cent, with no significant difference between treatment groups. In this cohort of W&W patients, the vast majority received SCRT with or without chemotherapy and results consistent with previous W&W reports were obtained. No statistically significant differences in terms of regrowth rate were obtained when comparing CRT, SCRT with chemotherapy, and SCRT alone. SCRT can induce sustained cCR and may precede a W&W strategy.

Project description:BackgroundOvarian preservation treatment (OPT) was recommended in young women with early-stage endometrial cancer [superficial myometrial invasion (MI) and grades (G) 1/2-endometrioid adenocarcinoma (EEC)]. A radiomics nomogram was developed to assist radiologists in assessing the depth of MI and in selecting eligible patients for OPT.MethodsFrom February 2014 to May 2021, 209 G 1/2-EEC patients younger than 45 years (mean 39 ± 4.3 years) were included. Of them, 104 retrospective patients were enrolled in the primary group, and 105 prospective patients were enrolled in the validation group. The radiomics features were extracted based on multi-parametric magnetic resonance imaging, and the least absolute shrinkage and selection operator algorithm was applied to reduce the dimensionality of the data and select the radiomics features that correlated with the depth of MI in G 1/2-EEC patients. A radiomics nomogram for evaluating the depth of MI was developed by combing the selected radiomics features with the cancer antigen 125 and tumor size. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic performance of the radiomics nomogram and of radiologists without and with the aid of the radiomics nomogram. The net reclassification index (NRI) and total integrated discrimination index (IDI) based on the total included patients to assess the clinical benefit of radiologists with the radiomics nomogram were calculated.ResultsIn the primary group, for evaluating the depth of MI, the AUCs were 0.96 for the radiomics nomogram; 0.80 and 0.86 for radiologists 1 and 2 without the aid of the nomogram, respectively; and 0.98 and 0.98 for radiologists 1 and 2 with the aid of the nomogram, respectively. In the validation group, the AUCs were 0.88 for the radiomics nomogram; 0.82 and 0.83 for radiologists 1 and 2 without the aid of the nomogram, respectively; and 0.94 and 0.94 for radiologists 1 and 2 with the aid of the nomogram, respectively. The yielded NRI and IDI values were 0.29 and 0.43 for radiologist 1 and 0.23 and 0.37 for radiologist 2, respectively.ConclusionsThe radiomics nomogram outperformed radiologists and could help radiologists in assessing the depth of MI and selecting eligible OPTs in G 1/2-EEC patients.

Dataset Information

Biomarker-based treatment selection in early-stage rectal cancer to promote organ preservation.

Background

Methods

Results

Publications

Biomarker-based treatment selection in early-stage rectal cancer to promote organ preservation.

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