Imaging biomarkers for risk stratification in colorectal and anal cancer

Introduction: “Imaging biomarkers” (IB) are radiological measurements that predict outcomes. Although IBs have been validated for primary colorectal cancer none are available for predicting disease relapse in colorectal or anal cancer. The aim of this thesis was to develop and implement IBs for relapse in colorectal and anal cancer. Methods: A systematic review assessed the completeness of reporting of IB publications in colorectal liver metastases. Potential IBs for anal SCC and mrTRG response assessment in rectal cancer were tested retrospectively. Finally IB implementation was tested by retrospectively and then prospectively assessing the potential role of DW-MRI as a screening tool for synchronous liver metastases in colorectal cancer. Results: Systematic review (n=30) found no IB studies adhered to REMARK but there were areas of good practice. mrT staging and mr-derived depth of extramural spread (DEMS) both predicted for outcome in 131 anal SCC patients, but when combined DEMS >12mm was the only predictor of outcome. mrTRG response in 338 patients predicted for recurrent or metastatic disease (OR 3.6) and described patterns of disease. Retrospectively DW-MRI detected more synchronous liver metastases in high-risk rectal cancer than CT (OR 8.065, P=0.018) with poorer 3 year OS (p<0.05). This led to the multicentre SERENADE study which aimed to validate screening DW-MRI in 262 patients; interim analysis showed DW-MRI detected 5% more synchronous liver metastases than CT. Conclusions and Future Work: REMARK should be required by journals publishing IB work. DEMS is a novel potential IB for anal SCC which could result in a change to TNM staging but first requires external validation against outcomes. Findings related to mrTRG and the timing and site of metastases should be considered when planning follow-up. Risk-adapted screening for liver metastases with DW-MRI has been validated and should be adopted in clinical practice for high-risk patients.Open Acces

Assessing the use of magnetic resonance imaging virtopsy as an alternative to autopsy: a systematic review and meta-analysis

Background The post mortem examination or autopsy is a trusted method of identifying the cause of death. Patients and their families may oppose an autopsy for a variety of reasons, including fear of mutilation or owing to religious and personal beliefs. Imaging alternatives to autopsy have been explored, which may provide a viable alternative. Objective To explore the possibility of using MRI virtopsy to establish the cause of death as an alternative to the traditional post mortem examination or autopsy. Methods Systematic review was carried out of all studies, without language restriction, identified from Medline, Cochrane (1960-2016) and Embase (1991-2016) up to December 2016. Further searches were performed using the bibliographies of articles and abstracts. All studies reporting the diagnosis of the cause of death by both MRI virtopsy and traditional autopsy were included. Results Five studies with 107 patients, contributed to a summative quantitative outcome in adults. The combined sensitivity of MRI virtopsy was 0.82 (95% CI 0.56 to 0.94) with a diagnostic odds ratio (DOR) of 11.1 (95% CI 2.2 to 57.0). There was no significant heterogeneity between studies (Q=1.96, df=4, p=0.75, I-2=0). Eight studies, with 953 patients contributed to a summative quantitative outcome in children. The combined sensitivity of MRI virtopsy was 0.73 (95% CI 0.59 to 0.84) with a DOR of 6.44 (95% CI 1.36 to 30.51). There was significant heterogeneity between studies (Q=34.95, df=7, p<0.01, I-2=80). Conclusion MRI virtopsy may offer a viable alternative to traditional autopsy. By using MRI virtopsy, a potential cost reduction of at least 33% is feasible, and therefore ought to be considered in eligible patients

Prediction of risk of distant recurrence using the 21-gene recurrence score in node-negative and node-positive postmenopausal patients with breast cancer treated with anastrozole or tamoxifen: a TransATAC Study

Purpose: To determine whether the Recurrence Score (RS) provided independent information on risk of distant recurrence (DR) in the tamoxifen and anastrozole arms of the Arimidex, Tamoxifen, Alone or in Combination (ATAC) Trial. Patients and Methods: RNA was extracted from 1,372 tumor blocks from postmenopausal patients with hormone receptor positive primary breast cancer in the monotherapy arms of ATAC. Twenty-one genes were assessed by quantitative reverse transcriptase polymerase chain reaction, and the RS was calculated. Cox proportional hazards models assessed the value of adding AS to a model with clinical variables (age, tumor size, grade, and treatment) in node-negative (NO) and node-positive (N+) women. Results: Reportable scores were available from 1,231 evaluable patients (NO, n = 872; N+, n = 306; and node status unknown, n = 53); 72, 74, and six DRs occurred in NO, N+, and node status unknown patients, respectively. For both NO and N+ patients, AS was significantly associated with time to DR in multivariate analyses (P < .001 for NO and P = .002 for N+). AS also showed significant prognostic value beyond that provided by Adjuvant! Online (P < .001). Nine-year DR rates in low (RS < 18), intermediate (RS = 18 to 30), and high RS (RS≥31) groups were 4%, 12%, and 25%, respectively, in NO patients and 17%, 28%, and 49%, respectively, in N+ patients. The prognostic value of AS was similar in anastrozole- and tamoxifen-treated patients. Conclusion: This study confirmed the performance of AS in postmenopausal HR+ patients treated with tamoxifen in a large contemporary population and demonstrated that AS is an independent predictor of DR in NO and N+ hormone receptor positive patients treated with anastrozole, adding value to estimates with standard clinicopathologic features

Global variation in postoperative mortality and complications after cancer surgery: a multicentre, prospective cohort study in 82 countries

© 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 licenseBackground: 80% of individuals with cancer will require a surgical procedure, yet little comparative data exist on early outcomes in low-income and middle-income countries (LMICs). We compared postoperative outcomes in breast, colorectal, and gastric cancer surgery in hospitals worldwide, focusing on the effect of disease stage and complications on postoperative mortality. Methods: This was a multicentre, international prospective cohort study of consecutive adult patients undergoing surgery for primary breast, colorectal, or gastric cancer requiring a skin incision done under general or neuraxial anaesthesia. The primary outcome was death or major complication within 30 days of surgery. Multilevel logistic regression determined relationships within three-level nested models of patients within hospitals and countries. Hospital-level infrastructure effects were explored with three-way mediation analyses. This study was registered with ClinicalTrials.gov, NCT03471494. Findings: Between April 1, 2018, and Jan 31, 2019, we enrolled 15 958 patients from 428 hospitals in 82 countries (high income 9106 patients, 31 countries; upper-middle income 2721 patients, 23 countries; or lower-middle income 4131 patients, 28 countries). Patients in LMICs presented with more advanced disease compared with patients in high-income countries. 30-day mortality was higher for gastric cancer in low-income or lower-middle-income countries (adjusted odds ratio 3·72, 95% CI 1·70–8·16) and for colorectal cancer in low-income or lower-middle-income countries (4·59, 2·39–8·80) and upper-middle-income countries (2·06, 1·11–3·83). No difference in 30-day mortality was seen in breast cancer. The proportion of patients who died after a major complication was greatest in low-income or lower-middle-income countries (6·15, 3·26–11·59) and upper-middle-income countries (3·89, 2·08–7·29). Postoperative death after complications was partly explained by patient factors (60%) and partly by hospital or country (40%). The absence of consistently available postoperative care facilities was associated with seven to 10 more deaths per 100 major complications in LMICs. Cancer stage alone explained little of the early variation in mortality or postoperative complications. Interpretation: Higher levels of mortality after cancer surgery in LMICs was not fully explained by later presentation of disease. The capacity to rescue patients from surgical complications is a tangible opportunity for meaningful intervention. Early death after cancer surgery might be reduced by policies focusing on strengthening perioperative care systems to detect and intervene in common complications. Funding: National Institute for Health Research Global Health Research Unit

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

© 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licenseBackground: Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide. Methods: A multimethods analysis was performed as part of the GlobalSurg 3 study—a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital. Findings: Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3·85 [95% CI 2·58–5·75]; p<0·0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63·0% vs 82·7%; OR 0·35 [0·23–0·53]; p<0·0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer. Interpretation: Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised. Funding: National Institute for Health and Care Research