Use of Contrast Media During CT-guided Thermal Ablation of Colorectal Liver Metastasis for Procedure Planning is Associated with Improved Immediate Outcomes.

PURPOSE: The aim of this study was to analyze the impact of using intra-procedural pre-ablation contrast-enhanced CT prior to percutaneous thermal ablation (pre-ablation CECT) of colorectal liver metastases (CLM) on local outcomes. MATERIALS AND METHODS: This retrospective analysis of a prospectively collected liver ablation registry included 144 consecutive patients (median age 57 years IQR [49, 65], 60% men) who underwent 173 CT-guided ablation sessions for 250 CLM between October 2015 and March 2020. In addition to oncologic outcomes, technical success was retrospectively evaluated using a biomechanical deformable image registration software for 3D-minimal ablative margin (3D-MAM) quantification. Bayesian regression was used to estimate effects of pre-ablation CECT on residual unablated tumor, 3D-MAM, and local tumor progression-free survival (LTPFS). RESULTS: Pre-ablation CECT was acquired in 71/173 (41%) sessions. Residual unablated tumor was present in one (0.9%) versus nine tumors (6.6%) ablated with versus without using pre-ablation CECT, respectively (p = 0.024). Pre-ablation CECT use decreased the odds of residual disease on first follow-up by 78% (CI95% [5, 86]) and incomplete ablation (3D-MAM ≤ 0 mm) by 58% (CI95% [13, 122]). The odds ratio for residual unablated tumor for larger CLM was lower when pre-ablation CECT was used (odds ratio 1.0 with pre-ablation CECT vs. 2.52 without). Pre-ablation CECT use was not associated with improvements on LTPFS. CONCLUSIONS: Pre-ablation CECT is associated with improved immediate outcomes by significantly reducing the incidence of residual unablated tumor and by mitigating the risk of incomplete ablation for larger CLM. We recommend performing baseline intra-procedural pre-ablation CECT as a standard imaging protocol. LEVEL OF EVIDENCE: Level 3 (retrospective cohort study).

Effect of Multimodal Prehabilitation on Reducing Postoperative Complications and Enhancing Functional Capacity Following Colorectal Cancer Surgery: The PREHAB Randomized Clinical Trial.

Importance: Colorectal surgery is associated with substantial morbidity rates and a lowered functional capacity. Optimization of the patient's condition in the weeks prior to surgery may attenuate these unfavorable sequelae. Objective: To determine whether multimodal prehabilitation before colorectal cancer surgery can reduce postoperative complications and enhance functional recovery. Design, Setting, and Participants: The PREHAB randomized clinical trial was an international, multicenter trial conducted in teaching hospitals with implemented enhanced recovery after surgery programs. Adult patients with nonmetastasized colorectal cancer were assessed for eligibility and randomized to either prehabilitation or standard care. Both arms received standard perioperative care. Patients were enrolled from June 2017 to December 2020, and follow-up was completed in December 2021. However, this trial was prematurely stopped due to the COVID-19 pandemic. Interventions: The 4-week in-hospital supervised multimodal prehabilitation program consisted of a high-intensity exercise program 3 times per week, a nutritional intervention, psychological support, and a smoking cessation program when needed. Main Outcomes and Measures: Comprehensive Complication Index (CCI) score, number of patients with CCI score more than 20, and improved walking capacity expressed as the 6-minute walking distance 4 weeks postoperatively. Results: In the intention-to-treat population of 251 participants (median [IQR] age, 69 [60-76] years; 138 [55%] male), 206 (82%) had tumors located in the colon and 234 (93%) underwent laparoscopic- or robotic-assisted surgery. The number of severe complications (CCI score >20) was significantly lower favoring prehabilitation compared with standard care (21 of 123 [17.1%] vs 38 of 128 [29.7%]; odds ratio, 0.47 [95% CI, 0.26-0.87]; P = .02). Participants in prehabilitation encountered fewer medical complications (eg, respiratory) compared with participants receiving standard care (19 of 123 [15.4%] vs 35 of 128 [27.3%]; odds ratio, 0.48 [95% CI, 0.26-0.89]; P = .02). Four weeks after surgery, 6-minute walking distance did not differ significantly between groups when compared with baseline (mean difference prehabilitation vs standard care 15.6 m [95% CI, -1.4 to 32.6]; P = .07). Secondary parameters of functional capacity in the postoperative period generally favored prehabilitation compared with standard care. Conclusions and Relevance: This PREHAB trial demonstrates the benefit of a multimodal prehabilitation program before colorectal cancer surgery as reflected by fewer severe and medical complications postoperatively and an optimized postoperative recovery compared with standard care. Trial Registration: trialregister.nl Identifier: NTR5947.

Interactive training versus self-driven training in the prediction of colorectal polyp histology by trainees using the NICE classification.

BACKGROUND: The COVID-19 pandemic has impacted endoscopic training of the Narrow Band Imaging International Colorectal Endoscopic (NICE) classification, which could accurately predict pathology of colorectal polyps. This study aimed to evaluate the diagnostic performance by trainees of self-driven training vs. interactive training in the prediction of colorectal polyp histology. METHODS: This was a prospective randomized controlled study at five academic centers from January 1, 2021 to May 31, 2021. Trainees with no previous formal training of narrow band imaging or blue light imaging for prediction of colorectal polyp histology were randomly allocated to the self-driven training group or interactive training group. Before and after the training, all trainees were given 20 selected cases of colorectal polyp for testing. Their diagnostic performance was analyzed. RESULTS: Overall, the two training groups showed similar accuracy of NICE classification (79.3% vs. 78.1%; P = 0.637), vessel analysis (77.8% vs. 77.6%, P = 0.939), and surface pattern analysis (78.1% vs. 76.9%, P = 0.616). The accuracy of color analysis in the interactive training group was better (74.4% vs. 80.0%, P = 0.027). For high-confidence predictions, the self-driven training group showed higher accuracy of NICE classification (84.8% vs. 78.7%, P < 0.001) but no difference for analysis of color (79.6% vs. 81.0%), vessel pattern (83.0% vs. 78.5%), and surface pattern (81.8% vs. 78.5%). CONCLUSIONS: Overall, self-driven training showed comparable accuracy of NICE classification, vessel pattern, and surface pattern to interactive training, but lower accuracy of color analysis. This method showed comparable effectiveness and is more applicable than interactive training. It is worth spreading during the COVID-19 pandemic. Trial registration Name of the registry: Chinese Clinical Trial Registry, Trial registration number: ChiCTR2000031659, Date of registration: 06/04/2020, URL of trial registry record: http://www.chictr.org.cn/showproj.aspx?proj=51994.

Malignant polyps in the COVID-19 era: a population-based analysis.

BACKGROUND: Malignant polyps represent the early development of colorectal adenocarcinoma. During 2020, there was widescale rationing of health-care resources in response to the COVID-19 pandemic. In particular there was deferral of some colonoscopy procedures required for timely malignant polyp detection. This study sought to assess how these deferrals affected the diagnosis of malignant polyps. METHODS: A population wide analysis was performed of 2079 malignant polyps, diagnosed in Queensland, Australia from 2011 to 2020. A regression analysis, with 95% prediction intervals, was produced to determine whether there was a significant impact on the number of malignant polyps diagnosed in 2020 compared to previous years. Univariate statistical analysis of patient, procedural, and pathological variables was also performed. RESULTS: In 2020 there were 211 malignant polyps diagnosed, which was significantly lower than was predicted by the univariate regression analysis (r2  = 0.85, 95% prediction interval: 255.07-323.91, P < 0.001). These malignant polyps were less likely to be diagnosed in a private setting (P < 0.001), and exhibited significantly less depth of submucosal invasion (P = 0.017). There was no significant difference in the management strategy (polypectomy, resection or trans-anal resection) between 2011 and 2019 and 2020. CONCLUSION: Because of the significant decrease in the number of malignant polyps, and the natural history of the disease, it is expected that there will be an increase in more advanced colorectal adenocarcinomas presenting in 2021 and beyond. This has implications for healthcare resources, particularly in light of the ongoing strain on health departments as a result of the COVID-19 pandemic.

Third Asia-Pacific consensus recommendations on colorectal cancer screening and postpolypectomy surveillance.

The Asia-Pacific region has the largest number of cases of colorectal cancer (CRC) and one of the highest levels of mortality due to this condition in the world. Since the publishing of two consensus recommendations in 2008 and 2015, significant advancements have been made in our knowledge of epidemiology, pathology and the natural history of the adenoma-carcinoma progression. Based on the most updated epidemiological and clinical studies in this region, considering literature from international studies, and adopting the modified Delphi process, the Asia-Pacific Working Group on Colorectal Cancer Screening has updated and revised their recommendations on (1) screening methods and preferred strategies; (2) age for starting and terminating screening for CRC; (3) screening for individuals with a family history of CRC or advanced adenoma; (4) surveillance for those with adenomas; (5) screening and surveillance for sessile serrated lesions and (6) quality assurance of screening programmes. Thirteen countries/regions in the Asia-Pacific region were represented in this exercise. International advisors from North America and Europe were invited to participate.

The Impact of Virtual Cancer Care on Chemotherapy Delivery and Clinical Outcomes in Colorectal Cancer Patients Receiving Systemic Therapy: A Pre- and Intra-Pandemic Analysis.

(1) Background: The coronavirus 2019 pandemic has resulted in an abrupt transition to virtual oncology care worldwide. This study's objective is to evaluate chemotherapy delivery and clinical outcomes in patients on systemic treatment for colorectal cancer before and during the pandemic. (2) Methods: Clinical data was collected on patients with colorectal cancer receiving intravenous chemotherapy at The Ottawa Hospital from June 2019 to March 2021. Patients were stratified by whether they were started on chemotherapy pre-pandemic (June 2019-January 2020) or intra-pandemic (February 2020-March 2021). Multiple regression analysis was used to compare outcomes between pandemic periods; (3) Results: There were 220 patients included in this study. The proportion of virtual consultations (1.2% to 64.4%) and follow-up visits (5.2% to 83.3%) increased during the pandemic. There was no difference in the incidence of treatment delays (OR = 1.01, p = 0.78), chemotherapy dose reductions (OR = 0.99, p = 0.69), emergency department visits (OR = 1.23, p = 0.37) or hospitalizations (OR = 0.73, p = 0.43) between pandemic periods. A subgroup analysis revealed no difference in outcomes independent of the presence of metastases; (4) Conclusion: These findings serve as an important quality-care indicator and demonstrate that virtual oncology care appears safe in a cohort of high-risk colorectal cancer patients.

Is qFIT a useful tool in prioritising symptomatic patients referred with suspect colorectal cancer in the COVID-19 era?

Background: The COVID-19 pandemic is an evolving healthcare challenge causing secondary disruption of cancer services. Quantitative Faecal Immunochemical Testing (qFIT) has been established as a screening method in asymptomatic patients. We aim to assess its utility as a triage tool to prioritise investigations in symptomatic patients with suspected colorectal cancer. Methods: At the commencement of the COVID-19 pandemic a database was established to include patients awaiting red flag outpatient consultation or colonic investigations and new red flag referrals from March to June 2020. Patients were supplied with qFIT kits and returned results categorised into 3 priority groups according to the qFIT value. Group 1 >150µg Hb/g, Group 2 ≥10 to ≤150µg Hb/g and Group 3 <10µg Hb/g. Subsequent colonic evaluation was offered by colonoscopy or cross-sectional imaging with urgency determined by qFIT priority group. When identified colorectal cancer, inflammatory bowel disease or high-risk polyps were recorded as "significant colorectal pathology." Findings: Three hundred and seventeen patients were identified with data analysed on 290 patients. Colorectal malignancy was identified in 17 patients; 94% of these patients were in Group 1. A qFIT result >150 µg Hb/g had a sensitivity and specificity for colorectal cancer of 94.12% (95% CI 71.31-99.85) and 91.21% (95% CI 87.20-94.29) respectively. No malignancy was detected in Priority Group 3; negative predictive value of 100% (95% CI 98.06-100). Conclusions: In symptomatic, suspect lower GI cancer patients qFIT is a useful adjunct for prioritising patients and can be used to determine the urgency of colorectal investigations.

DENEB: Development of new criteria for curability after local excision of pathological T1 colorectal cancer using liquid biopsy.

According to the current international guidelines, high-risk patients diagnosed with pathological T1 (pT1) colorectal cancer (CRC) who underwent complete local resection but may have risk of developing lymph node metastasis (LNM) are recommended additional intestinal resection with lymph node dissection. However, around 90% of the patients without LNM are exposed to the risk of being overtreated due to the insufficient pathological criteria for risk stratification of LNM. Circulating tumor DNA (ctDNA) is a noninvasive biomarker for molecular residual disease and relapse detection after treatments including surgical and endoscopic resection of solid tumors. The CIRCULATE-Japan project includes a large-scale patient-screening registry of the GALAXY study to track ctDNA status of patients with stage II to IV or recurrent CRC that can be completely resected. Based on the CIRCULATE-Japan platform, we launched DENEB, a new prospective study, within the GALAXY study for patients with pT1 CRC who underwent complete local resection and were scheduled for additional intestinal resection with lymph node dissection based on the standard pathologic risk stratification criteria for LNM. The aim of this study is to explore the ability of predicting LNM using ctDNA analysis compared with the standard pathological criteria. The ctDNA assay will build new evidence to establish a noninvasive personalized diagnosis in patients, which will facilitate tailored/optimal treatment strategies for CRC patients.

The Impact of the COVID-19 Pandemic on Colorectal Cancer Patients in a Tertiary Center in Romania. Single Center Retrospective Study.

Background: The novel coronavirus, SARS-COV-2, was first reported in Wuhan, China in the end of 2019. To curb its spread, social distancing measures and new safety regulations were implemented which led to major disruptions in colorectal cancer care. It is however unknown how it influenced the Romanian colorectal cancer care. Methods and Material: We assessed the demographical, clinical, intraoperative and pathological data of our colorectal cancer patients, 302 in total, between 15.03.2019-14.03.2021. The first year's data was considered as the control group and the second one, the study (pandemic) group. Results: We observed a 12% decrease in colorectal cancer hospitalizations in the first year, 38,6% in the first six months. The rate of emergency admissions, colo/ileostomy formatting procedures, palliative resections, clinical metastasis was higher in the pandemic group. More advanced locoregional invasion, a higher tumor stage, higher rate of vascular, perineural invasion, positive resection margin, and a higher lymph node yield was seen after the restrictions were implemented. Conclusion: The COVID-19 pandemic and the response against it had a major effect on the colorectal cancer care in our country. The outcomes of these worse clinical and pathological findings are unknown, but it is important to do further research in this field. We think colorectal cancer care should have an absolute priority in future pandemics.

Evaluating potential delays and outcomes of patients undergoing surgical resection for locally advanced and recurrent colorectal cancer during a pandemic.

INTRODUCTION: The COVID-19 pandemic resulted in a significant disruption of colorectal cancer (CRC) care pathways. This study evaluates the management and outcomes of patients with primary locally advanced or recurrent CRC during the pandemic in a single tertiary referral centre. METHODS: Patients undergoing elective surgery for advanced or recurrent CRC with curative intent between March 2020 and March 2021 were identified. Following first multidisciplinary team discussion patients were broadly classified into two groups: straight to surgery (n=22, 45%) or neoadjuvant therapy followed by surgery (n=27, 55%). Primary outcome was COVID-19-related complication rate. RESULTS: Forty-nine patients with a median age of 66 years (interquartile range: 54-73) were included. No patients developed a COVID-19 infection or related complication during hospital admission. Significant delays were identified in the treatment pathway of patients in the straight to surgery group, mostly due to delays in referral from external centres. Nine of 22 patients in the straight to surgery group had evidence of tumour progression compared with 3 of 27 in the neoadjuvant group (p=0.015839). Seven of 27 patients in the neoadjuvant group showed evidence of tumour regression. During the study, surgical waiting times were reduced, and more operations were performed during the second wave of COVID-19. CONCLUSION: This study suggests that it is possible to mitigate the risks of COVID-19-related complications in patients undergoing complex surgery for locally advanced and recurrent CRC. Delay in surgical intervention is associated with tumour progression, particularly in patients who may not have neoadjuvant therapy. Efforts should be made to prioritise resources for patients requiring time-sensitive surgery for advanced and recurrent CRC.

Computational study, synthesis and evaluation of active peptides derived from Parasporin-2 and spike protein from Alphacoronavirus against colorectal cancer cells.

Parasporin-2Aa1 (PS2Aa1) is a toxic protein of 37 KDa (30 kDa, activated form produced by proteolysis) that was shown to be cytotoxic against specific human cancer cells, although its mechanism of action has not been elucidated yet. In order to study the role of some native peptide fragments of proteins on anticancer activity, here we investigated the cytotoxic effect of peptide fragments from domain-1 of PS2Aa1 and one of the loops present in the binding region of the virus spike protein from Alphacoronavirus (HCoV-229E), the latter according to scientific reports, who showed interaction with the human APN (h-APN) receptor, evidence corroborated through computational simulations, and thus being possible active against colon cancer cells. Peptides namely P264-G274, Loop1-PS2Aa, and Loop2-PS2Aa were synthesized using the Fmoc solid-phase synthesis and characterized by mass spectrometry (MS). Additionally, one region from loop 1 of HCoV-229E, Loop1-HCoV-229E, was also synthesized and characterized. The A4W-GGN5 anticancer peptide and 5-fluorouracil (5-FU) were taken as a control in all experiments. Circular dichroism revealed an α-helix structure for the peptides derived from PS2Aa1 (P264-G274, Loop1-PS2Aa, and Loop2-PS2Aa) and ß-laminar structure for the peptide derived from Alphacoronavirus spike protein Loop1-HCoV-229E. Peptides showed a hemolysis percentage of less than 20% at 100 µM concentration. Besides, peptides exhibited stronger anticancer activity against SW480 and SW620 cells after exposure for 48 h. Likewise, these compounds showed significantly lower toxicity against normal cells CHO-K1. The results suggest that native peptide fragments from Ps2Aa1 may be optimized as a novel potential cancer-therapeutic agents.

Bioinformatics and in-silico findings reveal medical features and pharmacological targets of biochanin A against colorectal cancer and COVID-19.

Severe mortality due to the COVID-19 pandemic resulted from the lack of effective treatment. Although COVID-19 vaccines are available, their side effects have become a challenge for clinical use in patients with chronic diseases, especially cancer patients. In the current report, we applied network pharmacology and systematic bioinformatics to explore the use of biochanin A in patients with colorectal cancer (CRC) and COVID-19 infection. Using the network pharmacology approach, we identified two clusters of genes involved in immune response (IL1A, IL2, and IL6R) and cell proliferation (CCND1, PPARG, and EGFR) mediated by biochanin A in CRC/COVID-19 condition. The functional analysis of these two gene clusters further illustrated the effects of biochanin A on interleukin-6 production and cytokine-cytokine receptor interaction in CRC/COVID-19 pathology. In addition, pathway analysis demonstrated the control of PI3K-Akt and JAK-STAT signaling pathways by biochanin A in the treatment of CRC/COVID-19. The findings of this study provide a therapeutic option for combination therapy against COVID-19 infection in CRC patients.

Impact of the COVID-19 pandemic on the management of colorectal cancer in Denmark.

INTRODUCTION: The COVID-19 pandemic has had a global impact on cancer care but the extent to which this has affected the management of colorectal cancer (CRC) in different countries is unknown. CRC management in Denmark was thought to have been relatively less impacted than in other nations during the first wave of the pandemic. The aim of this study was to determine the pandemic's impact on CRC in Denmark. METHODS: The Danish national cancer registry identified patients with newly diagnosed with CRC from 1 March 2020 to 1 August 2020 (pandemic interval) and corresponding dates in 2019 (prepandemic interval). Data regarding clinicopathological demographics and perioperative outcomes were retrieved and compared between the two cohorts. RESULTS: Total CRC diagnoses (201 versus 359 per month, P = 0.008) and screening diagnoses (38 versus 80 per month, P = 0.016) were both lower in the pandemic interval. The proportions of patients presenting acutely and the stage at presentation were, however, unaffected. For those patients having surgery, both colonic and rectal cancer operations fell to about half the prepandemic levels: colon (187 (i.q.r. 183-188) to 96 (i.q.r. 94-112) per month, P = 0.032) and rectal cancers (63 (i.q.r. 59-75) to 32 (i.q.r. 28-42) per month, P = 0.008). No difference was seen in surgical practice or postoperative 30-day mortality rate (colon 2.2 versus 2.2 per cent, P = 0.983; rectal 1.0 versus 2.9 per cent, P = 0.118) between the cohorts. Treatment during the pandemic interval was not independently associated with death at 30 or 90 days. CONCLUSION: The initial wave of the COVID-19 pandemic reduced the number of new diagnoses made and number of operations but had limited impact on technique or outcomes of CRC care in Denmark.

Neutrophil Extracellular Traps in Colorectal Cancer Progression and Metastasis.

Neutrophils form sticky web-like structures known as neutrophil extracellular traps (NETs) as part of innate immune response. NETs are decondensed extracellular chromatin filaments comprising nuclear and cytoplasmic proteins. NETs have been implicated in many gastrointestinal diseases including colorectal cancer (CRC). However, the regulatory mechanisms of NET formation and potential pharmacological inhibitors in the context of CRC have not been thoroughly discussed. In this review, we intend to highlight roles of NETs in CRC progression and metastasis as well as the potential of targeting NETs during colon cancer therapy.

Curative treatments for colon cancer during the COVID-19 pandemic era.

During the coronavirus disease 2019 (COVID-19) pandemic, to protect patients with cancer, reduction in hospital access, reduction in myelosuppression risk, and postponing/withholding unnecessary treatments were important in order to reduce risk of infection. Little is known about the risk burden for patients with resected colorectal cancer (CRC). Use of an oral chemotherapy regimen represents a convenient, safe, and manageable therapy for both fit and elderly patients. In the metastatic setting, treatment of solitary metastases may be performed, omitting postresection chemotherapy due to lack of literature data. In case of unresectable CRC, short induction chemotherapy, followed by a maintenance phase, may improve compliance and reduce toxicity. In the adjuvant setting, a shorter duration (3 months) may be discussed with patients except in very high-risk cases. Clinical judgment may reduce the risk of COVID-19 exposure in patients with CRC. Oral regimens, treatment delay, and chemotherapy holiday are ways to minimize the global risk for patients during the COVID-19 era.

Association of COVID-19 Lockdown With the Tumor Burden in Patients With Newly Diagnosed Metastatic Colorectal Cancer.

Importance: The COVID-19 pandemic has been associated with substantial reduction in screening, case identification, and hospital referrals among patients with cancer. However, no study has quantitatively examined the implications of this correlation for cancer patient management. Objective: To evaluate the association of the COVID-19 pandemic lockdown with the tumor burden of patients who were diagnosed with metastatic colorectal cancer (mCRC) before vs after lockdown. Design, Setting, and Participants: This cohort study analyzed participants in the screening procedure of the PANIRINOX (Phase II Randomized Study Comparing FOLFIRINOX + Panitumumab vs FOLFOX + Panitumumab in Metastatic Colorectal Cancer Patients Stratified by RAS Status from Circulating DNA Analysis) phase 2 randomized clinical trial. These newly diagnosed patients received care at 1 of 18 different clinical centers in France and were recruited before or after the lockdown was enacted in France in the spring of 2020. Patients underwent a blood-sampling screening procedure to identify their RAS and BRAF tumor status. Exposures: mCRC. Main Outcomes and Measures: Circulating tumor DNA (ctDNA) analysis was used to identify RAS and BRAF status. Tumor burden was evaluated by the total plasma ctDNA concentration. The median ctDNA concentration was compared in patients who underwent screening before (November 11, 2019, to March 9, 2020) vs after (May 14 to September 3, 2020) lockdown and in patients who were included from the start of the PANIRINOX study. Results: A total of 80 patients were included, of whom 40 underwent screening before and 40 others underwent screening after the first COVID-19 lockdown in France. These patients included 48 men (60.0%) and 32 women (40.0%) and had a median (range) age of 62 (37-77) years. The median ctDNA concentration was statistically higher in patients who were newly diagnosed after lockdown compared with those who were diagnosed before lockdown (119.2 ng/mL vs 17.3 ng/mL; P < .001). Patients with mCRC and high ctDNA concentration had lower median survival compared with those with lower concentration (14.7 [95% CI, 8.8-18.0] months vs 20.0 [95% CI, 14.1-32.0] months). This finding points to the potential adverse consequences of the COVID-19 pandemic and related lockdown. Conclusions and Relevance: This cohort study found that tumor burden differed between patients who received an mCRC diagnosis before vs after the first COVID-19 lockdown in France. The findings of this study suggest that CRC is a major area for intervention to minimize pandemic-associated delays in screening, diagnosis, and treatment.

Do clinical trials change practice? A longitudinal, international assessment of colorectal cancer prescribing practices.

INTRODUCTION: Over half of the 1.5 million individuals globally who are diagnosed with colorectal cancer (CRC) present with stage II-III disease. Understanding clinician attitudes towards treatment for this group is paramount to contextualise real-world outcomes and plan future trials. The aim of this study was to assess clinician awareness of trials assessing the optimal duration of CRC adjuvant therapy, their attitudes towards shorter treatment and their self-reported practice. METHODS: A survey was developed using OnlineSurveys® and distributed to clinicians in April 2019, with a follow-up survey disseminated to a subset of respondents in August 2020. Microsoft Excel® and Stata® were used for analysis. RESULTS: 265 clinicians replied to the first survey, with the majority aware of findings from the International Duration Evaluation of Adjuvant Therapy collaboration and contributory trials. Practice change was greatest for patients under 70 with low-risk stage III CRC, with most uncertainty around using 3-months of doublet chemotherapy for high-risk stage II disease. In August 2020, clinicians (n = 106) were more likely to use 3-months of FOLFOX for low-risk stage III disease and 3-months of CAPOX for stage II disease compared to April 2019. There was no indication that the COVID-19 pandemic had enduring changes on treatment decisions beyond those made in response to trial evidence. DISCUSSION: Clinicians use a risk-stratified approach to treat CRC the adjuvant setting. Lower utilisation of doublet chemotherapy for older and stage II patients has affected the extent of trial implementation. Active dialogue regarding how trial results apply to these groups may improve consensus.

CIRCULATE-Japan: Circulating tumor DNA-guided adaptive platform trials to refine adjuvant therapy for colorectal cancer.

Adjuvant chemotherapy has reduced the risk of tumor recurrence and improved survival in patients with resected colorectal cancer. Potential utility of circulating tumor DNA (ctDNA) prior to and post surgery has been reported across various solid tumors. We initiated a new type of adaptive platform trials to evaluate the clinical benefits of ctDNA analysis and refine precision adjuvant therapy for resectable colorectal cancer, named CIRCULATE-Japan including three clinical trials. The GALAXY study is a prospectively conducted large-scale registry designed to monitor ctDNA for patients with clinical stage II to IV or recurrent colorectal cancer who can undergo complete surgical resection. The VEGA trial is a randomized phase III study designed to test whether postoperative surgery alone is noninferior to the standard therapy with capecitabine plus oxaliplatin for 3 months in patients with high-risk stage II or low-risk stage III colon cancer if ctDNA status is negative at week 4 after curative surgery in the GALAXY study. The ALTAIR trial is a double-blind, phase III study designed to establish the superiority of trifluridine/tipiracil as compared with placebo in patients with resected colorectal cancer who show circulating tumor-positive status in the GALAXY study. Therefore, CIRCULATE-Japan encompasses both "de-escalation" and "escalation" trials for ctDNA-negative and -positive patients, respectively, and helps to answer whether measuring ctDNA postoperatively has prognostic and/or predictive value. Our ctDNA-guided adaptive platform trials will accelerate clinical development toward further precision oncology in the field of adjuvant therapy. Analysis of ctDNA status could be utilized as a predictor of risk stratification for recurrence and to monitor the effectiveness of adjuvant chemotherapy. ctDNA is a promising, noninvasive tumor biomarker that can aid in tumor monitoring throughout disease management.