Symptoms and General Pathology

All Conditions

Neoplasms

Recurrence

Cicatrix

Neoplasm Recurrence, Local

Disease Attributes

Neoplastic Processes

EMR scar is interrogated using WLE followed by NBI

EMR scar is interrogated using NBI followed by WLE

EMR scar is inspected using WLE followed by NBI or vice versa

WLE followed by NBI or NBI followed by WLE (crossover design)

Miguel Areia, PhD

Nowadays endoscopic mucosal resection (EMR) is the gold standard for the removal of large laterally spreading and sessile colorectal lesions ≥ 20 mm. However, recurrence rate after successful EMR (defined by the absence of neoplastic tissue at the completion of the procedure after careful inspection of the post-EMR mucosal defect and margin) is about 15-20%. Consequently, current guidelines recommend a surveillance colonoscopy between 4 and 6 months after resection for detection of residual or recurrent polyp.

There are few studies that have examined the accuracy of advanced endoscopic imaging for the prediction of histological recurrence but none of these imaging modalities have been validated for surveillance after EMR. Therefore, current guidelines strongly recommend systematic biopsy of EMR scar.

The main aim of this study is to assess the incremental benefit of narrow band imaging (NBI) and white light endoscopy (WLE) randomizing the initial technique for the endoscopic detection of post-EMR recurrence and to asses if this advanced imaging method achieve sufficient diagnostic accuracy to exclude recurrence without the need for biopsy.

a. Study type: multicenter randomized crossover trial: i. prospective inclusion of consecutive patients undergoing first follow-up surveillance colonoscopy after successful EMR of colorectal lesion; ii. crossover randomization by computer generated tables; iii. allocation concealment by sealed, opaque envelopes; iv. pathologist-blinded - pathologists are blinded to the study protocol and samples are received as 'EMR scar for assessment' .

b. Selection patient method: inclusion by invitation of patients undergoing the first follow-up surveillance colonoscopy after successful EMR of colorectal lesion.

c. Sample size: 210 (two groups of 105 patients). To improve accuracy from 85% (value obtained by a study that did not show significant differences in the accuracy of NBI followed by WLE vs. WLE followed by NBI) to 95% and assuming a normal distribution and a power of 80% (α=0.05), the calculated sample size of each of the 2 groups was 96; allowing for a 10% dropout rate, the sample size is 105 per group (210 patients overall).

d. Procedures and data collection methods: i. Each procedure is performed by the same endoscopist. ii. All patients receive split dose bowel preparation. iii. All colonoscopies are performed using high definition colonoscopes with NBI ( EVIS EXERA III CV 185 and CV 190; Olympus Inc., Tokyo, Japan). iv. Colon inspection is done with WLE during withdrawal. v. At the proximity of the scar WLE and NBI were used randomly one after the other (WLE\>NBI or NBI\>WLE). If NBI is the first technique used, it is switched prior to scar detection, avoiding, as far as possible, a glance with WLE. The edges of the scar are interrogated followed by the centre of the scar and finding are recorded. vi. After both evaluations, if there is no suspicion of recurrence, the site is sampled by at least 2 biopsies of the scar edge. If there is any suspicion of recurrence, tissue sample is obtained and then treated by endoscopic resection using standard methods. At least 2 biopsies specimens from normal appearing scar are also obtained.

e. Analysed variables: i. patient characteristics; ii. data from baseline colonoscopy; iii. data from first surveillance colonoscopy (see outcome measures).

f. Statistical analysis: i. Performed using statistical software IBM SPSS Statistics, Version 25.0. Armonk, NY: IBM Corp. ii. Continuous variables are reported as mean and standard deviation or median and interquartile range, if they have normal or not normal distribution, respectively; categorical variables as absolute and relative frequency. iii. Continuous variables are compared between two groups using Student's T test if they have a normal distribution and homogeneity of variance or Mann-Whitney U if these conditions are not met. Categorical variables are compared using Pearson's X2 test or Fisher test. iv. Sensitivity, specificity, negative and positive predictive values and accuracy are calculated using 2x2 contingency tables. v. All hypotheses are two-tailed and a P-value\<0.05 is considered statistically significant.

Follow-up Protocol of Colorectal Endoscopic Mucosal Resection Scars

Follow-up Protocol of Colorectal Endoscopic Mucosal Resection Scars: a Multicentre Randomized Single-blinded Crossover Trial

Sensitivity, specificity, negative predictive value, positive predictive value and accuracy of NBI and WLE for each group calculated using 2x2 contingency tables

WLE recurrent adenoma identification for each group

NBI recurrent adenoma identification for each group

Adenoma recurrence confirmed by histology

Lesion size and location, Paris classification, NICE classification, number of pieces, use of adjunctive ablative techniques and those identification and histology. Data collected by endoscopic reports consultation

Scar size, presence or absence of recurrence, in case of recurrence: number of sites, location (edge of the scar, within the scar or both), morphology of recurrence, NICE classification (for NBI evaluation)

Portuguese Oncology Institute, Coimbra

Medical Doctor

Skin and Connective Tissue Diseases

Breast Neoplasms

Carcinoma

Hyperplasia

Carcinoma, Intraductal, Noninfiltrating

Breast Diseases

Skin Diseases

Adenocarcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Carcinoma in Situ

Breast Carcinoma In Situ

Bone Density Conservation Agents

Antineoplastic Agents

All Drugs and Chemicals

Anticoagulants

Other Dietary Supplements

Tamoxifen

Citric Acid

Sodium Citrate

Estrogens

Estrogen Antagonists

Estrogen Receptor Antagonists

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Selective Estrogen Receptor Modulators

Estrogen Receptor Modulators

Citrate

tamoxifen at daily dose of 5 mg for a total treatment time of 3 years

placebo at daily dose of 5 mg for a total treatment time of 3 years

placebo

Andrea DeCensi, MD

The aim of the study is to evaluate whether tamoxifen at a low dose of 5mg/d reduces in the long term the incidence of invasive breast cancer and ductal carcinoma in situ, DCIS (DIN 1c, 2, 3) of the breast, in woman operated for lobular intraepithelial neoplasia (LIN1, 2 and 3) or ER-positive ductal intraepithelial neoplasia (DIN 1b, DIN2, DIN3, 1a excluded) of the breast.

To improve the risk-benefit ratio, the use of lower doses of the drug has been proposed.

Biomarker trials revealed that 5 mg/d was noninferior to 20 mg/d in inhibiting proliferation of breast cancer and normal endometrial tissue.

By contrast, the risk of endometrial cancer si dose-dependent, and the dose reduction can lead a substantial decrease. Morover a dose of 5 mg/day is associated with an overall decrease of the estrogenic activity of tamoxifen on insulin like growth factor (IGF-I), sex hormone-binding globulin (SHBG) and antithrombin-III, with a decrease of venous thromboembolic events. Moreover, tamoxifen exhibits a high tissue distribution, so that a dose of 5 mg/day attains at the breast tissue level a concentration 10 times higher than that needed to inhibit cell growth in vitro.

A prospective cohort study also showed that 10 mg on alternate days halves recurrence of DCIS in postmenopausal women.

It has been shown that the treatment of dysplasia or pre-cancer drives the reduction of the invasive neoplasms onset. This is a chemoprevention trial designed to validatate the low-dose Tamoxifen in women with diseases at high evolutionary risk. The demonstration of efficacy and safety of such a treatment for the prevention of the invasive breast cancer would lead improvements in term of survival and quality of life for the patients at increased risk.

Italian, multicenter, phase III trial: controlled, parallel group comparision, randomized (1:1) duble blind, tamoxifen 5 mg/d versus placebo administered for 3 years. A total of 500 women 75 years of age or younger with newly diagnosed non-invasive breast cancer have been included in the study. The long-term study implies a minimum 10 year follow up after treatment completion.

Trial of Low Dose Tamoxifen in Women With Breast Intraepithelial Neoplasia - Long Term Follow-up

Randomized Placebo-controlled Phase III Trial of Low Dose Tamoxifen in Women With Breast Intraepithelial Neoplasia - Long Term Follow-up

Authors are open to share data based on a request for collaboration that includes a data analysis plan.

Please send an e-mail to both: andrea.decensi@galliera.it; mpuntoni@ao.pr.it

Number of neoplastic events, i.e., invasive breast cancer or ductal carcinoma in situ of the breast from the start of treatment up to at least 16 years from treatment initiation.

Number of other non-invasive breast disorders (LCIS, atypical ductal or lobular hyperplasia), endometrial cancer, ovarian cancer, thromboembolic events; bone fractures, cardiovascular and thromboembolic events, clinically manifested cataracts and melanoma; change of mammographic density from the start of treatment up to at least 16 years from treatment initiation.

Blood concentrations of metabolites including circulating IGF-I,IGFBP-3, SHBG, hormones (testosterone, estradiol, SHBG, CRP), tamoxifen metabolites (4OH tamoxifen and endoxifen).

Esploratory analisis of some SNPS of the cytochrome P450 genes involved in tamoxifen metabolism such as CYP2D6.

Associazione Italiana per la Ricerca sul Cancro

European Institute of Oncology

Andrea DeCensi

Medical Oncology Director

Adenoma

Colonic Polyps

Polyps

Intestinal Polyps

Pathological Conditions, Anatomical

Post procedural prophylactic coagulation of the entire margin of the resection site creating a 2-3mm rim.

Thermal ablation of the entire resection margin

Snare tip soft coagulation

Gijs Kemper, MD

Gijs Kemper

Peter Siersema

The primary objective of this trial is to investigate whether thermal ablation EMR with soft tip snare coagulation (STSC) reduces the recurrence rate of lateral spreading or sessile polyps ≥20mm compared to standard EMR.

Rationale:

Lowering the EMR recurrence rate will potentially lead to fewer colonoscopies resulting in less additional costs, less compliance burdens and less exposure to possible procedure related risks.

Objective:

To investigate whether thermal ablation EMR with snare tip soft coagulation (STSC) reduces the recurrence rate of lateral spreading or sessile polyps ≥20mm compared to standard EMR.

Study design:

This study entails a patient-blinded multicenter prospective randomized controlled trial that will be conducted between January 2022 and May 2025 in 1 academic and 7 non-academic hospitals in The Netherlands and it will take place in the outpatient clinics of the participating centers.

Study population:

All patients aged ≥ 18 years with proven colorectal sessile of lateral spreading polyps (Paris classification 0-IIa/b/c, Is) with a diameter of ≥ 20mm requiring piecemeal resection with EMR are eligible for inclusion.

Intervention:

Snare tip soft coagulation of the entire EMR margin is a technique for the removal of potential residual adenoma.

Main study endpoint:

Polyp recurrence after 6 months follow up. Recurrence is evaluated histologically and endoscopically with biopsies taken during follow up colonoscopy.

Recurrences After Standard EMR vs Plus Thermal Ablation EMR

Recurrences After Standard EMR vs Plus Thermal Ablation EMR of Advanced Sessile and Lateral Spreading Colorectal Adenoma

There is no particular plan. But the investigators are willing to share the data with colleagues depending which research question they want to answer.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Follow-up Protocol of Colorectal Endoscopic Mucosal Resection Scars	NCT04239365	Colorectal Canc... Recurrence, Loc...	WLE followed by...	18 Years -	Portuguese Oncology Institute, Coimbra
Trial of Low Dose Tamoxifen in Women With Breast Intraepithelial Neoplasia - Long Term Follow-up	NCT01357772	Carcinoma, Intr... Recurrence, Loc... Breast Neoplasm... Atypical Hyperp...	Tamoxifen placebo	18 Years - 75 Years	Ente Ospedaliero Ospedali Galliera
Trial of Low Dose Tamoxifen in Women With Breast Intraepithelial Neoplasia - Long Term Follow-up	NCT01357772	Carcinoma, Intr... Recurrence, Loc... Breast Neoplasm... Atypical Hyperp...	Tamoxifen placebo	18 Years - 75 Years	Ente Ospedaliero Ospedali Galliera
Recurrences After Standard EMR vs Plus Thermal Ablation EMR	NCT05121805	Polyps of Colon Recurrence, Loc...	Snare tip soft ...	18 Years -	Radboud University Medical Center
Recurrences After Standard EMR vs Plus Thermal Ablation EMR	NCT05121805	Polyps of Colon Recurrence, Loc...	Snare tip soft ...	18 Years -	Radboud University Medical Center

Spots Global Cancer Trial Database for recurrence, local neoplasm