Defining response to radiotherapy in rectal cancer using magnetic resonance imaging and histopathological scales

Aim: To define good and poor regression using pathology and MRI regression scales after neo-adjuvant chemotherapy for rectal cancer. Methods: A systematic review of all studies up to December 2015, without language restriction that were identified from MEDLINE, Cochrane Controlled Trials Register (1960–2015), and EMBASE (1991–2015). Searches were performed of article bibliographies and conference abstracts. MeSH and text words, included “tumour regression”, “mrTRG”, “poor response” and “colorectal cancers”. Clinical studies using either MRI or histopathological TRG scales to define good and poor responders were included in relation to outcomes (local (LR), distant recurrence (DR), disease free (DFS), overall survival (OS)). There was no age restriction to included patients nor stage of cancer.Data was extracted by two authors independently using pre-defined outcome measures. Results: Quantitative data (prevalence) were extracted and analysed according to meta-analytical techniques using comprehensive meta-analysis. Qualitative data (LR, DR, DFS &OS) were presented as ranges. The overall proportion of poor responders after neo-adjuvant CRT was 37.7% (CI: 30.1 to 45.8). There were 19 different reported histopathological scales and one MRI regression scale (mrTRG). Clinical studies used nine and six histopathological scales for poor and good responders respectively. All studies using MRI to define good and poor response used one scale. The most common histopathological definition for good response was the Mandard grades 1&2 or Dworak grades 3&4; Mandard 3,4&5 and Dworak 0,1&2 were used for poor response. For histopathological grades, the 5-year outcomes for poor responders were LR 3.4-4.3%, DR 14.3-20.3%, DFS 61.7-68.1% and OS 60.7-69.1. Good pathological response 5-year outcomes were LR, 0-1.8%; DR, 0-11.6%; DFS, 78.4-86.7%; and, OS, 77.4-88.2%. A poor response on MRI (mrTRG 4,5) resulted in 5-year LR 4-29%, DR 9%, DFS 31-59% and OS 27-68%. The 5-year outcomes with a good response on MRI (mrTRG 1,2 & 3) was LR 1-14%, DR 3%, DFS 64-83% and OS 72-90%. Conclusions: For histopathology regression assessment Mandard1,2/Dworak3,4 should be used for good and Mandard3,4,5/Dworak0,1,2 for poor response. MRI indicates good and poor response by mrTRG1-3 and mrTRG4-5 respectively

Interobserver agreement of radiologists assessing the response of rectal cancers to preoperative chemoradiation using the MRI tumour regression grading (mrTRG)

AIM: To investigate whether the magnetic resonance imaging (MRI) tumour regression grading (mrTRG) scale can be taught effectively resulting in a clinically reasonable interobserver agreement (>0.4; moderate to near perfect agreement). MATERIALS AND METHODS: This study examines the interobserver agreement of mrTRG, between 35 radiologists and a central reviewer. Two workshops were organised for radiologists to assess regression of rectal cancers on MRI staging scans. A range of mrTRGs on 12 patient scans were used for assessment. RESULTS: Kappa agreement ranged from 0.14–0.82 with a median value of 0.57 (95% CI: 0.37–0.77) indicating good overall agreement. Eight (26%) radiologists had very good/near perfect agreement (κ>0.8). Six (19%) radiologists had good agreement (0.8≥κ>0.6) and a further 12 (39%) had moderate agreement (0.6≥κ>0.4). Five (16%) radiologists had a fair agreement (0.4≥κ>0.2) and two had poor agreement (0.2>κ). There was a tendency towards good agreement (skewness: 0.92). In 65.9% and 90% of cases the radiologists were able to correctly highlight good and poor responders, respectively. CONCLUSIONS: The assessment of the response of rectal cancers to chemoradiation therapy may be performed effectively using mrTRG. Radiologists can be taught the mrTRG scale. Even with minimal training, good agreement with the central reviewer along with effective differentiation between good and intermediate/poor responders can be achieved. Focus should be on facilitating the identification of good responders. It is predicted that with more intensive interactive case-based learning a κ>0.8 is likely to be achieved. Testing and retesting is recommended

Local and distant recurrences in rectal cancer patients are predicted by the nonspecific immune response; specific immune response has only a systemic effect - a histopathological and immunohistochemical study

BACKGROUND: Invasion and metastasis is a complex process governed by the interaction of genetically altered tumor cells and the immunological and inflammatory host reponse. Specific T-cells directed against tumor cells and the nonspecific inflammatory reaction due to tissue damage, cooperate against invasive tumor cells in order to prevent recurrences. Data concerning involvement of individual cell types are readily available but little is known about the coordinate interactions between both forms of immune response. PATIENTS AND METHODS: The presence of inflammatory infiltrate and eosinophils was determined in 1530 patients with rectal adenocarcinoma from a multicenter trial. We selected 160 patients to analyze this inflammatory infiltrate in more detail using immunohistochemistry. The association with the development of local and distant relapses was determined using univariate and multivariate log rank testing. RESULTS: Patients with an extensive inflammatory infiltrate around the tumor had lower recurrence rates (3.4% versus 6.9%, p = 0.03), showing the importance of host response against tumor cells. In particular, peritumoral mast cells prevent local and distant recurrence (44% versus 15%, p = 0.007 and 86% versus 21%, p < 0.0001, respectively), with improved survival as a consequence. The presence of intratumoral T-cells had independent prognostic value for the occurrence of distant metastases (32% versus 76%, p < 0.0001). CONCLUSIONS: We showed that next to properties of tumor cells, the amount and type of inflammation is also relevant in the control of rectal cancer. Knowledge of the factors involved may lead to new approaches in the management of rectal cancer

Should the surgeon or the general practitioner (GP) follow up patients after surgery for colon cancer? A randomized controlled trial protocol focusing on quality of life, cost-effectiveness and serious clinical events

This trial has been registered at ClinicalTrials.gov. The trial registration number is: NCT00572143.© 2008 Augestad et al; licensee BioMed Central Ltd.This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0),which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Evaluation of appendicitis risk prediction models in adults with suspected appendicitis

Background Appendicitis is the most common general surgical emergency worldwide, but its diagnosis remains challenging. The aim of this study was to determine whether existing risk prediction models can reliably identify patients presenting to hospital in the UK with acute right iliac fossa (RIF) pain who are at low risk of appendicitis. Methods A systematic search was completed to identify all existing appendicitis risk prediction models. Models were validated using UK data from an international prospective cohort study that captured consecutive patients aged 16–45 years presenting to hospital with acute RIF in March to June 2017. The main outcome was best achievable model specificity (proportion of patients who did not have appendicitis correctly classified as low risk) whilst maintaining a failure rate below 5 per cent (proportion of patients identified as low risk who actually had appendicitis). Results Some 5345 patients across 154 UK hospitals were identified, of which two‐thirds (3613 of 5345, 67·6 per cent) were women. Women were more than twice as likely to undergo surgery with removal of a histologically normal appendix (272 of 964, 28·2 per cent) than men (120 of 993, 12·1 per cent) (relative risk 2·33, 95 per cent c.i. 1·92 to 2·84; P < 0·001). Of 15 validated risk prediction models, the Adult Appendicitis Score performed best (cut‐off score 8 or less, specificity 63·1 per cent, failure rate 3·7 per cent). The Appendicitis Inflammatory Response Score performed best for men (cut‐off score 2 or less, specificity 24·7 per cent, failure rate 2·4 per cent). Conclusion Women in the UK had a disproportionate risk of admission without surgical intervention and had high rates of normal appendicectomy. Risk prediction models to support shared decision‐making by identifying adults in the UK at low risk of appendicitis were identified

An audit comparing the reporting of staging MRI scans for rectal cancer with the London Cancer Alliance (LCA) guidelines.

This article focuses on the audit and assessment of clinical practice before and after introduction of MRI reporting guidelines. Standardised proforma based reporting may improve quality of MRI reports. Uptake of the use may be facilitated by endorsement from regional and national cancer organisations.This audit was divided into 2 phases. MRI reports issued between April 2014 and June 2014 were included in the first part of our audit. Phase II included MRI reports issued between April 2015 and June 2015.14 out of 15 hospitals that report MRI scans in the LCA responded to our audit proposal. The completion rate of key MRI metrics/metrics was better in proforma compared to prose reports both before (98% vs 73%; p < 0.05) and after introduction of the guidelines (98% vs 71%; p < 0.05). There was an approximate doubling of proforma reporting after the introduction of guidelines and workshop interventions (39% vs 65%; p < 0.05). Evaluation of locally advanced cancers (tumours extending to or beyond the circumferential resection margin) for beyond TME surgery was reported in 3% of prose reports vs. 42% in proformas.Incorporation of standardised reporting in official guidelines improved the uptake of proforma based reporting. Proforma based reporting captured more MRI reportable items compared to prose summaries, before and after the implementation of guidelines. MRI reporting of advanced cancers for beyond TME surgery falls short of acceptable standards but is more detailed in proforma based reports. Further work to improve completion especially in beyond TME reporting is required

Significance of extranodal tumour deposits in colorectal cancer: A systematic review and meta-analysis.

Aims The presence and significance of extranodal tumour deposits (ENTDs) in colorectal cancer (CRC) continue to cause controversy in terms of origin, classification and prognostic significance. This review aims to assess current evidence on the origin of ENTDs in CRC and their effect on overall and disease-free survival.Methods A systematic review and meta-analysis were carried out in accordance with the Preferred Reporting Items for Systematic reviews and Meta-analyses (PRISMA) guidelines. End-points included prevalence of ENTDs, relationship with extramural venous invasion (EMVI), overall survival (OS) and disease-free survival (DFS). Pooled hazard ratios (HRs) and odds ratios (ORs) were calculated using Stata software.Results Twenty-six studies comprising 19,980 patients were included. The prevalence of ENTDs ranged from 10.2% to 44.2% (median 21.3%). There was a significantly increased odds of having ENTD if EMVI was present with a pooled OR of 2.51 (95% CI 2.27-2.77) p ≤ 0.001. The pooled HR for adverse OS in patients with ENTD was 1.63 (95% CI 1.44-1.61), p ≤ 0.001. For adverse DFS the pooled HR was 1.77 (95% CI 1.37-2.11), p ≤ 0.001.Conclusion This meta-analysis confirms the negative impact of ENTDs on OS and DFS despite variations in classification and prevalence. ENTDs are significantly associated with EMVI. The prognostic implications of ENTDs are not sufficiently recognised in current staging systems. TNM 8 has failed to address this and has not made use of the available evidence to determine the correct position of ENTDs according to their prognostic effect. The prognostic hierarchy should be N0, N1, N2 with N1c being the most severe. Additionally the exclusion of lesions of vascular, lymphatic and perineural origin by TNM 8 has no evidence base