Long-term outcomes of clinical complete responders after neoadjuvant treatment for rectal cancer in the International Watch & Wait Database (IWWD): an international multicentre registry study

Medical imaging can assess the tumor and its environment in their entirety, which makes it suitable for monitoring the temporal and spatial characteristics of the tumor. Progress in computational methods, especially in artificial intelligence for medical image process and analysis, has converted these images into quantitative and minable data associated with clinical events in oncology management. This concept was first described as radiomics in 2012. Since then, computer scientists, radiologists, and oncologists have gravitated towards this new tool and exploited advanced methodologies to mine the information behind medical images. On the basis of a great quantity of radiographic images and novel computational technologies, researchers developed and validated radiomic models that may improve the accuracy of diagnoses and therapy response assessments. Here, we review the recent methodological developments in radiomics, including data acquisition, tumor segmentation, feature extraction, and modelling, as well as the rapidly developing deep learning technology. Moreover, we outline the main applications of radiomics in diagnosis, treatment planning and evaluations in the field of oncology with the aim of developing quantitative and personalized medicine. Finally, we discuss the challenges in the field of radiomics and the scope and clinical applicability of these methods.

The Applications of Radiomics in Precision Diagnosis and Treatment of Oncology: Opportunities and Challenges.

Purpose: To develop and validate a radiomics model for evaluating pathologic complete response (pCR) to neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer (LARC).Experimental Design: We enrolled 222 patients (152 in the primary cohort and 70 in the validation cohort) with clinicopathologically confirmed LARC who received chemoradiotherapy before surgery. All patients underwent T2-weighted and diffusion-weighted imaging before and after chemoradiotherapy; 2,252 radiomic features were extracted from each patient before and after treatment imaging. The two-sample t test and the least absolute shrinkage and selection operator regression were used for feature selection, whereupon a radiomics signature was built with support vector machines. Multivariable logistic regression analysis was then used to develop a radiomics model incorporating the radiomics signature and independent clinicopathologic risk factors. The performance of the radiomics model was assessed by its calibration, discrimination, and clinical usefulness with independent validation.Results: The radiomics signature comprised 30 selected features and showed good discrimination performance in both the primary and validation cohorts. The individualized radiomics model, which incorporated the radiomics signature and tumor length, also showed good discrimination, with an area under the receiver operating characteristic curve of 0.9756 (95% confidence interval, 0.9185-0.9711) in the validation cohort, and good calibration. Decision curve analysis confirmed the clinical utility of the radiomics model.Conclusions: Using pre- and posttreatment MRI data, we developed a radiomics model with excellent performance for individualized, noninvasive prediction of pCR. This model may be used to identify LARC patients who can omit surgery after chemoradiotherapy. Clin Cancer Res; 23(23); 7253-62. ©2017 AACR.

https://clincancerres.aacrjournals.org/content/clincanres/23/23/7253.full.pdf

Radiomics Analysis for Evaluation of Pathological Complete Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer

Importance Treatment of locally advanced rectal (LARC) cancer involves chemoradiation, surgery, and chemotherapy. The concept of total neoadjuvant therapy (TNT), in which chemoradiation and chemotherapy are administered prior to surgery, has been developed to optimize delivery of effective systemic therapy aimed at micrometastases. Objective To compare the traditional approach of preoperative chemoradiation (chemoRT) followed by postoperative adjuvant chemotherapy with the more recent TNT approach for LARC. Design, Setting, and Participants A retrospective cohort analysis using Memorial Sloan Kettering Cancer Center (MSK) records from 2009 to 2015 was carried out. A total of 811 patients who presented with LARC (T3/4 or node-positive) were identified. Exposures Of the 811 patients, 320 received chemoRT with planned adjuvant chemotherapy and 308 received TNT (induction fluorouracil- and oxaliplatin-based chemotherapy followed by chemoRT). Main Outcomes and Measures Treatment and outcome data for the 2 cohorts were compared. Dosing and completion of prescribed chemotherapy were assessed on the subset of patients who received all therapy at MSK. Results Of the 628 patients overall, 373 (59%) were men and 255 (41%) were women, with a mean (SD) age of 56.7 (12.9) years. Of the 308 patients in the TNT cohort, 181 (49%) were men and 127 (49%) were women. Of the 320 patients in the chemoRT with planned adjuvant chemotherapy cohort, 192 (60%) were men and 128 (40%) were women. Patients in the TNT cohort received greater percentages of the planned oxaliplatin and fluorouracil prescribed dose than those in the chemoRT with planned adjuvant chemotherapy cohort. The complete response (CR) rate, including both pathologic CR (pCR) in those who underwent surgery and sustained clinical CR (cCR) for at least 12 months posttreatment in those who did not undergo surgery, was 36% in the TNT cohort compared with 21% in the chemoRT with planned adjuvant chemotherapy cohort. Conclusions and Relevance Our findings provide additional support for the National Comprehensive Cancer Network (NCCN) guidelines that categorize TNT as a viable treatment strategy for rectal cancer. Our data suggest that TNT facilitates delivery of planned systemic therapy. Long-term follow-up will determine if this finding translates into improved survival. In addition, given its high CR rate, TNT may facilitate nonoperative treatment strategies aimed at organ preservation.

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Adoption of Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer.

A watch-and-wait approach for locally advanced rectal cancer after a clinical complete response following neoadjuvant chemoradiation: a systematic review and meta-analysis

Summary Background Induction of a clinical complete response with chemoradiotherapy, followed by observation via a watch-and-wait approach, has emerged as a management option for patients with rectal cancer. We aimed to address the shortage of evidence regarding the safety of the watch-and-wait approach by comparing oncological outcomes between patients managed by watch and wait who achieved a clinical complete response and those who had surgical resection (standard care). Methods Oncological Outcomes after Clinical Complete Response in Patients with Rectal Cancer (OnCoRe) was a propensity-score matched cohort analysis study, that included patients of all ages diagnosed with rectal adenocarcinoma without distant metastases who had received preoperative chemoradiotherapy (45 Gy in 25 daily fractions with concurrent fluoropyrimidine-based chemotherapy) at a tertiary cancer centre in Manchester, UK, between Jan 14, 2011, and April 15, 2013. Patients who had a clinical complete response were offered management with the watch-and-wait approach, and patients who did not have a complete clinical response were offered surgical resection if eligible. We also included patients with a clinical complete response managed by watch and wait between March 10, 2005, and Jan 21, 2015, across three neighbouring UK regional cancer centres, whose details were obtained through a registry. For comparative analyses, we derived one-to-one paired cohorts of watch and wait versus surgical resection using propensity-score matching (including T stage, age, and performance status). The primary endpoint was non-regrowth disease-free survival from the date that chemoradiotherapy was started, and secondary endpoints were overall survival, and colostomy-free survival. We used a conservative p value of less than 0·01 to indicate statistical significance in the comparative analyses. Findings 259 patients were included in our Manchester tertiary cancer centre cohort, 228 of whom underwent surgical resection at referring hospitals and 31 of whom had a clinical complete response, managed by watch and wait. A further 98 patients were added to the watch-and-wait group via the registry. Of the 129 patients managed by watch and wait (median follow-up 33 months [IQR 19–43]), 44 (34%) had local regrowths (3-year actuarial rate 38% [95% CI 30–48]); 36 (88%) of 41 patients with non-metastatic local regrowths were salvaged. In the matched analyses (109 patients in each treatment group), no differences in 3-year non-regrowth disease-free survival were noted between watch and wait and surgical resection (88% [95% CI 75–94] with watch and wait vs 78% [63–87] with surgical resection; time-varying p=0·043). Similarly, no difference in 3-year overall survival was noted (96% [88–98] vs 87% [77–93]; time-varying p=0·024). By contrast, patients managed by watch and wait had significantly better 3-year colostomy-free survival than did those who had surgical resection (74% [95% CI 64–82] vs 47% [37–57]; hazard ratio 0·445 [95% CI 0·31–0·63; p Interpretation A substantial proportion of patients with rectal cancer managed by watch and wait avoided major surgery and averted permanent colostomy without loss of oncological safety at 3 years. These findings should inform decision making at the outset of chemoradiotherapy. Funding Bowel Disease Research Foundation.

/pdf/watch-and-wait-approach-versus-surgical-resection-after-37ua3cikgd.pdf

Watch-and-wait approach versus surgical resection after chemoradiotherapy for patients with rectal cancer (the OnCoRe project): a propensity-score matched cohort analysis

Abdominal closure in the presence of enterocutaneous fistula, stoma or infection can be challenging. A single-surgeon’s experience of performing components separation abdominal reconstruction and reinforcement with mesh in the difficult abdomen is presented. Medical records from patients undergoing components separation and reinforcement with hernia mesh at Royal Liverpool Hospital from 2009 to 2012 were reviewed. Patients were classified by the Ventral Hernia Working Group (VHWG) grading system. Co-morbidities, previous surgeries, specific type of reconstruction technique, discharge date, complications and hernia recurrence were recorded. Twenty-three patients’ (15 males, 8 females) notes were reviewed. Median age was 57 years (range 20-76 years). Median follow-up at the time of review was 17 months (range 2-48 months). There were 13 grade III hernias and 10 grade IV hernias identified. Synthetic mesh was placed to reinforce the abdomen in 6 patients, cross-linked porcine dermis was used in 3, and a Biodesign® Hernia Graft was placed in 14. Complications included wound infection (13%), superficial wound dehiscence (22%), seroma formation (22%) and stoma complications (9%). To date, hernias have recurred in 3 patients (13%). Components separation and reinforcement with biological mesh is a successful technique in the grade III and IV abdomen with acceptable rate of recurrence and complications.

https://link.springer.com/content/pdf/10.1186%2F1471-2482-14-25.pdf

Abdominal wall reconstruction with components separation and mesh reinforcement in complex hernia repair

Background Acute uncomplicated diverticulitis (AUD) is common and antibiotics are the cornerstone of traditional conservative management. This approach lacks clear evidence base and studies have recently suggested that avoidance of antibiotics is a safe and efficacious way to manage AUD. The aim of this systematic review is to determine the safety and efficacy of treating AUD without antibiotics. Methods A systematic search of Embase, Cochrane library, MEDLINE, Science Citation Index Expanded, and ClinicalTrials. gov was performed. Studies comparing antibiotics versus no antibiotics in the treatment of AUD were included. Meta-analysis was performed using the random effects model with the primary outcome measure being diverticulitis-associated complications. Secondary outcomes were readmission rate, diverticulitis recurrence, mean hospital stay, requirement for surgery and requirement for percutaneous drainage. Results Eight studies were included involving 2469 patients; 1626 in the non-antibiotic group (NAb) and 843 in the antibiotic group (Ab). There was a higher complication rate in the Ab group however this was not significant (1.9% versus 2.6%) with a combined risk ratio (RR) of 0.63 (95% CI, 0.25 to 1.57, p=0.32). There was a shorter mean length of hospital stay in the Nab group (standard mean difference of -1.18 (95% CI, -2.34 to -0.03 p= 0.04). There was no significant difference in readmission, recurrence and surgical intervention rate or requirement for percutaneous drainage. Conclusion Treatment of AUD without antibiotics may be feasible with outcomes that are comparable to antibiotic treatment and with potential benefits for patients and the NHS. Large scale randomised multicentre studies are needed. This article is protected by copyright. All rights reserved.

Antibiotics versus no antibiotics in the treatment of acute uncomplicated diverticulitis - a systematic review and meta-analysis.

Objectives To establish the prevalence of small, flat carcinomas in surgically resected colon. To determine whether tumour morphology influences stage at presentation.



Method  1763 surgically resected colorectal cancers from one UK centre excised between 1995 and 2004 were examined. Age 69 years, (42–90), M:F equal. Sixty-one tumours 20 mm across were identified. Slides were reviewed by a consultant histopathologist and classified using Japanese Research Society Classification, JRSC and TNM staging. Fisher's exact test was used for analysis.



Results  In 61 small cancers, 64% (39/61) showed flat morphology and 33% (20/61) polypoid. Two lesions were unclassifiable. Prevalence was 2.2% of all resected colorectal cancers. More T1 tumours at presentation were polypoid, (30% vs. 8%; P = 0.033). T3 tumours were more likely to be flat than polypoid, (49% vs. 20%; P = 0.016). Infiltration into musclaris mucosa occurred in 77% (30/39) flat tumours. Rates of metastases were high in both groups, (30% polypoid vs. 39% flat, not significant).



Conclusions  The prevalence of small, flat cancers in resected specimens in the UK concurs with that of Japanese studies. Small, flat cancers should be staged carefully because of high rates of T3/4 disease. The results support the theory of accelerated carcinogenesis in flat cancers.

Small, flat colorectal cancers in the UK population: an analysis of resected specimens

Single-stage repair of incisional hernias in contaminated fields has a high rate of surgical site infection (30–42%) when biologic grafts are used for repair. In an attempt to decrease this risk, a novel graft incorporating gentamicin into a biologic extracellular matrix derived from porcine small intestine submucosa was developed. This prospective, multicenter, single-arm observational study was designed to determine the incidence of surgical site infection following implantation of the device into surgical fields characterized as CDC Class II, III, or IV. Twenty-four patients were enrolled, with 42% contaminated and 25% dirty surgical fields. After 12 months, 5 patients experienced 6 surgical site infections (21%) with infection involving the graft in 2 patients (8%). No grafts were explanted. The incorporation of gentamicin into a porcine-derived biologic graft can be achieved with no noted gentamicin toxicity and a low rate of device infection for patients undergoing single-stage repair of ventral hernia in contaminated settings. The study was registered March 27, 2015 at www.clinicaltrials.gov as NCT02401334.

https://link.springer.com/content/pdf/10.1186/s12893-020-00715-w.pdf

Paul S Rooney

Papers

Watch-and-wait approach versus surgical resection after chemoradiotherapy for patients with rectal cancer (the OnCoRe project): a propensity-score matched cohort analysis

Abdominal wall reconstruction with components separation and mesh reinforcement in complex hernia repair

Antibiotics versus no antibiotics in the treatment of acute uncomplicated diverticulitis - a systematic review and meta-analysis.

Small, flat colorectal cancers in the UK population: an analysis of resected specimens

Single-stage repair of contaminated hernias using a novel antibiotic-impregnated biologic porcine submucosa tissue matrix.