Stage II-III Colorectal Cancer Research Articles

Application and Prognostic Analysis of Vacuum Sealing Drainage in the Incision Infection in Patients With Stage II-III Colorectal Cancer.

This study aims to explore the application value of vacuum sealing drainage (VSD) technology in the treatment of incision infection dehiscence after surgery in patients with stage II-III colorectal cancer and analyze its impact on prognosis. This retrospective study included patients who experienced incision infection dehiscence after surgery for colorectal cancer between February 2014 and August 2019. Clinical and pathological data, short-term outcomes, and long-term outcomes were compared between the traditional group and the VSD group. A total of 97 patients were included in this study. There was no significant difference in clinical and pathological data between the traditional group and the VSD group (P > 0.05). The VSD group had fewer dressing changes, lower pain scores during dressing changes, and better granulation tissue growth grading than the traditional group, with statistical significance (P < 0.05). The VSD group started adjuvant chemotherapy earlier and had a higher proportion of ≥4 cycles of chemotherapy. The three-year overall survival rate in the VSD group was better than the traditional group, but the difference was not statistically significant (P > 0.05). The application of VSD technology can promote granulation tissue growth, accelerate incision healing, and facilitate patients to complete subsequent adjuvant chemotherapy. However, further verification of its long-term impact on prognosis requires longer-term follow-up results.

Measure of minimal residual burden on circulating tumor cells with over-expression of programmed death-ligand 1 as a dynamic biomarker in patients with colorectal cancer.

e14553 Background: In stage III colorectal cancer (CRC) patients, the extent of oxaliplatin-combination as an adjuvant therapy is still undetermined. Approx. 25-50% Stage II-III CRC patients are known to develop recurrence and metastasis even after comprehensive treatment, attributed to occult disease and Minimal Residual Disease (MRD). Circulating Tumor Cells (CTCs) are bio-mechanistic extravasation source for micro-metastatic disease. CRC patients, with lower adjuvant therapy from 3 to 6 months are known to exhibit increased CTCs and positivity rate due to the emergence of resistant clones. Assays to detect CTCs and expression of Programmed Cell Death-Ligand 1 (PD-L1) as a dynamic biomarker simultaneously has wide clinical implications. Especially, when the tissue biopsy is not inadequate to detect molecular targets for immune checkpoint inhibitor (ICT) therapy. Methods: Retrospectively, 182 CRC cancer patients were analyzed for the presence of CTC and distribution at baseline and follow-ups (up to 0-4 follow ups). The peripheral blood 1.5 ml was analyzed using the OncoDiscover platform approved by CDSCO, India consisting multifunctional magneto-nanosystem mediated by anti-epithelial cellular adhesion molecule (EpCAM) antibody. CTCs were analyzed in patients with early stages- pre and post treatment, progressive disease, Disease Free Status (DFS) and in metastasis. The isolated cells were immune-stained to detect CK-18 +ve, CD45 -ve, DAPI +ve and PD-L1 +ve expression. PD-L1 expression in CTCs was validated by analyzing the linear intensity gradients of the fluorescence signals. CTCs were termed as PD-L1 -ve based on a weak or no detectable fluorescence signal and termed +ve based on a high fluorescence signal using automated image acquisition Zeiss microscope. Results: In a cohort of 182 CRC patient samples, n = 128 (70.3 %) showed the presence of CTCs. The fluorescence intensity for PD-L1 expression as a robust functional assay on CTCs for molecular characterization was developed. The distribution of CTCs ranged from 1-9. The mean fluorescence intensity value and cut-off for the expression of PD-L1 in CTCs was accounted to be ~1.02. Interestingly, in n = 54 (42.2 %) patients, CTCs showed positive expression of PD-L1. CTC +ve patients with PD-L1 expression were associated at all stages and even in early stage, progressive disease, and metastasis. Patients without any CTCs n = 54 (29.7%) either had clinically stable disease or were in DFS with no radio-graphical image. Conclusions: The presence of PD-L1 over-expression on CTCs is a dynamic biomarker in blood, showing the progression of disease even in patients with DFS status. CTC enumeration and assessing the PD-L1 expression on CTCs could offer highly individualized treatment plans in CRC patients.

Cumulative Incidence, Risk Factors, and Overall Survival of Disease Recurrence after Curative Resection of Stage II-III Colorectal Cancer: A Population-based Study.

Population-based data on recurrent colorectal cancer are rare, but crucial for counseling patients and their physicians. This large nationwide, population-based study provides an up-to-date overview of the epidemiology of recurrent disease in patients with stage II and III primary colon and rectal cancer treated with surgical resection.

Abstract B106: Assessing racial disparities in the receipt of quality care in the most prevalent cancers in American Indians

Abstract INTRODUCTION Previous SEER-Medicare analyses reported lower receipt of guideline concordant care for American Indian (AI) compared with White (WH) patients across several cancers. While large scale assessments are informative, there is a need to assess cancer outcomes and develop interventions at a level closer to communities. To address this gap, we assessed measures of quality care in AI and WH breast, prostate, and colorectal cancer patients. METHODS We assembled novel cohorts of AI and WH patients from the North Carolina (NC) cancer registry, the state with the largest AI population east of the Mississippi River. Eligible patients were diagnosed with breast, prostate, and colorectal cancers who linked to public and private insurance claims with continuous enrollment (2003-2019). Measures were assessed within 1 year of diagnosis unless stated otherwise. Breast cancer measures included receipt of: (1) HER2 testing within 3 months of diagnosis [NQF #1878]; (2) Tamoxifen/Aromatase Inhibitors for Stage I-III ER/PR+ [NQF #220]; (3) radiation among stage I-III breast conserving surgery or mastectomy patients [NQF #0219]. Stage II-III colorectal cancer measures included receipt of: (1) carcinoembryonic antigen (CEA) testing; (2) surveillance colonoscopy; and (3) computed tomography (CT) among resected patients [NCCN 2.2023 COL-8]. We assessed receipt of prostate-specific antigen (PSA) testing in the first 15 months after prostate cancer diagnosis to monitor disease recurrence. Poisson regression adjusting for sex, urbanicity, insurance type, and age at diagnosis was used to estimate risk ratios (RR) and 95% confidence intervals (CI) comparing the receipt of care between AI and WH patients. RESULTS The sample sizes of AI patients differed across measures, ranging from 104 colorectal to 554 prostate cancer patients. Evidence of disparity was mixed for the breast cancer measures. AI breast cancer patients less frequently received HER2 testing within 3 months of diagnosis (AI=61% vs WH=71%), although adjustment attenuated this association (RR=0.90; CI: 0.81-1.01). Among stage I-III breast cancer patients, AIs more frequently received radiation within 1 year of surgery (AI=75% vs WH=71%) compared with WH patients (RR=1.11; CI: 1.01-1.21). Across colorectal cancer measures, AI patients performed as well or better than WH patients. Notably, AI patients more frequently received CEA testing (AI=71% vs WH=59%), a difference that persisted after adjustment (RR=1.17; CI: 1.03-1.32). AI prostate cancer patients received PSAs less often in the 15 months following diagnosis (AI=82% vs WH=88%) than WH patients (RR=0.96; CI: 0.93-1.00). CONCLUSIONS The magnitude and direction of AI/WH disparities in receipt of quality cancer care differed across measures. Racial misclassification is a challenge in AI health outcomes research, which may misrepresent the experience of AIs. Nevertheless, our findings provide insight into specific areas of breast, prostate, and colorectal cancer care where local tailored interventions can be focused to improve care equity. Citation Format: Bradford E. Jackson, Marc E. Emerson, Lisa P. Spees, Chris D. Baggett, Hayley N. Morris, Ana I. Salas, Angelo Moore, Yadurshini Raveendran, Clare Meernik, Tomi Akinyemiju, Rachel Denlinger-Apte, Ronny A. Bell, Stephanie B. Wheeler. Assessing racial disparities in the receipt of quality care in the most prevalent cancers in American Indians [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B106.

Impact of Postoperative Naples Prognostic Score to Predict Survival in Patients with Stage II-III Colorectal Cancer.

The Naples prognostic score (NPS) is a scoring system that reflects a patient's systemic inflammatory and nutritional status. This study aimed to evaluate whether postoperative NPS is effective in assessing the prognosis of stage II-III colorectal cancer (CRC) patients compared with preoperative NPS. Between 2005 and 2012, a total of 164 patients diagnosed with stage II-III CRC, who underwent curative resection followed by adjuvant chemotherapy, were divided into two groups: Group 0-1 (NPS = 0-2) and Group 2 (NPS = 3 or 4). Preoperative NPS was calculated based on the results before surgeries, and postoperative NPS was assessed using the results obtained before adjuvant chemotherapy. The overall survival of Group 0-1 was higher than that of Group 2 in both pre- and postoperative NPS assessments. According to the ROC curve analysis, the Area Under the Curve (AUC) ratio for postoperative NPS was 0.64, compared with 0.57 for preoperative NPS, 0.52 for the preoperative neutrophil-lymphocyte ratio (p = 0.032), and 0.51 for the preoperative platelet-lymphocyte ratio (p = 0.027). Postoperative NPS is effective in predicting the prognosis of stage II-III CRC patients who underwent curative resection followed by adjuvant chemotherapy. The use of NPS could be beneficial in evaluating the prognosis of CRC patients after surgeries.

The Prognostic Significance of Postoperative Adjuvant Chemotherapy in the Population Aged 75 Years and Older with Stage II-III Colorectal Cancer: A Retrospective Multi-Center Cohort Study.

It is common for elderly patients to be underrepresented in clinical trials for cancer, which can result in a lack of efficacy data and unclear criteria to guide treatment decisions for clinical doctors. Therefore, one of the common challenges in oncology treatment is determining the extent to which patients aged 75 and older have benefited from postoperative chemotherapy. The study aimed to explore the effect of adjuvant chemotherapy (AC) on 3-year recurrence-free survival (RFS) after curative resection in patients aged 75 years and older with stage II-III colorectal cancer (CRC). The retrospective cohort analysis was performed on patients with stage II-III CRC who received curative resection at three cancer centers in China between 2008 and 2017. Kaplan-Meier curves and Multivariable Cox regression models were used to analyze the impact of AC on RFS in patients. Finally, propensity-score matching was used to reduce selection bias and confounding factors in patients aged 75 years and older with stage II-III CRC. A total of 2885 patients were included (1729 (59.9%) male; 1312 (61.5%) received AC). The pre-matching cohort was comprised of 151 patients aged 75 years and older (median age (IQR)77.00 (76.00, 79.00); 97 (64.2%) male, 51 (72.9%) received AC). Age (P=0.001), postoperative carcinoembryonic antigen (CEA)(P=0.02) level were associated with prognosis. But AC was not associated with 3-year RFS (HR, 1.27; 95% CI, 0.80-2.0; log-rank P=0.37). After a predisposition 1: 1 match (with or without AC, n = 42), AC remains uncorrelated with 3-year RFS (HR, 1.39; 95% CI, 0.52-3.70; log-rank P=0.66). Patients over the age of 75 with stage II-III CRC who receive AC or do not face the same risk of postoperative recurrence. As a result, patients with stage II-III postoperative adjuvant chemotherapy can make an informed decision regarding whether they want to undergo chemotherapy based on their age and reduce the unnecessary side effects of chemotherapy.

PD-24 A novel molecular subtype for Chinese stage II-III colorectal cancer based on multi-center and large sample size data

PD-24 A novel molecular subtype for Chinese stage II-III colorectal cancer based on multi-center and large sample size data

Sex difference in tolerability of adjuvant oxaliplatin-based chemotherapy for colorectal cancer and changes in diagnostic components of sarcopenia: A prospective study.

e15625 Background: We previously reported that based on CT images at the 3rd lumbar vertebra, female patients with colorectal cancer (CRC) were more likely to be sarcopenic than male patients after curative resection, and predisposed to develop early dose limiting toxicities (DLTs) in adjuvant CAPOX therapy. Although oxaliplatin-based adjuvant chemotherapy for CRC is prevalently used worldwide, it is largely unknown how the treatment affects patients in terms of sarcopenia. Therefore we conducted a prospectively study on the impact of adjuvant chemotherapy on multifactorial components assessed for sarcopenia. Methods: We examined stage II-III CRC patients who received adjuvant CAPOX after curative surgery after March 2022. Informed consent was obtained from all participants. During this systemic therapy, we assessed nutritional status using Mini-Nutritional Assessment (MNA, an 18-item questionnaire consisting of psychological well-being, diet quality, physical activity and anthropometric metrics; score range:0-30), and examined gait speed and grip strength, as well as whole body skeletal muscle mass, fat mass, and bone mineral using a body composition analyzer. The changes in these metrics were analyzed in association with dose reduction/adverse events of CAPOX. All continuous variables were tested by Wilcoxon rank-sum test. Results: Eighteen men and 13 women (mean age: 61 years old) were included in this study. Seven (39%) male and seven (54%) female patients required dose reduction within the four treatment cycles (p = 0.65). The median MNA, gait speed, grip, muscle mass, fat mass and bone mineral at the first and fourth cycles of CAPOX in men were 20.4 and 24.0, 1.10 and 1.23 m/sec, 30.9 and 31.2 kg, 27.3 and 28.0 kg, 11.8 and 11.9 kg, and 2.8 and 2.9 kg, respectively. The median of these metrics at the first and fourth cycles of CAPOX in women were 21.4 and 22.4, 1.32 and 1.33 m/sec, 22.0 and 22.4 kg, 21.95 and 22.12 kg, 13.43 and 14.62 kg, and 2.34 and 2.31 kg, respectively. The relative values (medians) of the metrics at the fourth cycle to those at the first cycle of CAPOX (men vs women) were as follows; MNA:1.131 vs 1.045 (p = 0.057), gait speed:1.075 vs 0.950 (p = 0.17), grip:1.018 vs 1.044 (p = 0.81), muscle mass:1.028 vs 1.011 (p = 0.036), fat mass:1.029 vs 1.080 (p = 0.47), and bone mineral:1.030 vs 0.991 (p = 0.015). Conclusions: It is suggested that adjuvant CAPOX has negative impact on postoperative recovery of psychological and physical components in female patients.

Abstract 2306: Potential clinical utility of circulating tumor DNA detected by digital PCR in a nationwide Danish cohort of high-risk colorectal cancer patients

Abstract Introduction: Increasingly, circulating tumor DNA (ctDNA) is proposed as a tool for minimal residual disease (MRD) assessment, with the potential to guide postoperative treatment decisions. Low ctDNA levels immediately after surgery necessitate extremely sensitive detection methods. Additionally, for potential clinical implementation, detection methods should ideally feature short turnaround times (TATs) and low analysis costs. Compared to sequencing-based detection methods, digital PCR is low-cost, and features TATs of less than a day. Consequently, digital PCR is a good candidate for clinical implementation. Here, we present ctDNA detection results from a highly optimized, tumor-informed digital PCR strategy in a large cohort of stage II-III colorectal cancer (CRC) patients. Methods: Stage II-III CRC patients (n=864) treated with curative intent were recruited from Danish surgical centers from 2014 to 2021. Whole exome sequencing was conducted on matched tumor and buffy coat from all patients. After thorough clonality assessment, a mutational target was chosen for digital PCR analysis. Plasma samples (8mL) collected before and within 60 days after surgery, were investigated for ctDNA using digital PCR. Additionally, a subset of patients (n=229) had serial samples collected every three months analyzed for ctDNA. Results: Before surgery, ctDNA was detected in 569/828 (69%) analyzed blood samples. A minimum of 12 months of radiological follow-up was available for 598/864 patients at time of writing, enabling prognostic evaluation of ctDNA detection in these patients. Postoperative ctDNA detection was highly correlated to future recurrence (HR=9.6, 95%CI 6.3-15, P&amp;lt;0.001). The median time to recurrence was significantly shorter for postoperatively ctDNA positive patients (10 months, interquartile range (IQR) 3.8-12 months) compared to ctDNA negative patients (18 months, IQR 12-26 months, P&amp;lt;0.001), indicating a higher disease burden postoperatively in ctDNA positive patients. In a subset of patients with samples collected immediately after adjuvant treatment (n=95) and serially (n=186), ctDNA was also prognostic of recurrence (HR=6.4, CI95% 2.9-14, P&amp;lt;0.001; HR=27, 95%CI 14-52, P&amp;lt;0.001). A minimum of 12 months of follow-up is expected to be available for 700 patients before the AACR meeting 2023. Conclusion: These results from one of the largest ctDNA detection cohorts of stage II-III CRC patients demonstrate that our personalized digital PCR approach effectively detects MRD immediately after surgery. Additionally, our approach shows promise for serial ctDNA detection for recurrence surveillance applications. With digital PCR being a widespread and cost-effective method with low TATs, clinical implementation of ctDNA analysis may be more forthright using this method over cost-intensive sequencing-based methods. Citation Format: Tenna V. Henriksen, Christina Demuth, Amanda Frydendahl, Marijana Nesic, Mads H. Rasmussen, Thomas Reinert, Ole H. Larsen, Anders H. Madsen, Uffe S. Løve, Per V. Andersen, Ole Thorlacius-Ussing, Ismail Gögenur, Jakob Lykke, Allan G. Pedersen, Peter Bondeven, Nis H. Schlesinger, Lene H. Iversen, Kåre A. Gotschalck, Claus L. Andersen. Potential clinical utility of circulating tumor DNA detected by digital PCR in a nationwide Danish cohort of high-risk colorectal cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2306.

High resection rates of colorectal liver metastases after standardized follow-up and multimodal management: an outcome study within the COLOFOL trial

BackgroundOutcome after colorectal liver metastases (CRLM) resection has improved over time, despite increased resection rates. Hence, it's crucial to identify all patients possible to treat with curative intent. The objectives of this study were to map recurrence pattern, treatment strategy and survival depending on treatment and follow-up strategy. MethodsIn the COLOFOL-trial, patients with radically resected stage II-III colorectal cancer were randomized to high-frequency (6, 12, 18, 24 and 36 months; HF) or low-frequency (12 and 36 months; LF) follow-up. In this study, all CRLM within 5 years were identified and medical files scrutinized. Overall survival (OS) was analysed in uni- and multivariable analyses. Primary endpoint was 5-year OS. ResultsOf 2442 patients, 235 (9.6%) developed metachronous CRLM of which 123 (52.3%) underwent treatment with curative intent, resulting in 5-year OS of 58%. Five-year OS for patients with CRLM was 43% after HF versus 24% after LF. The survival benefit was confirmed for HF 8 years from resection of the primary tumour, HR 0.63 (CI 0.46–0.85). ConclusionA high proportion of metachronous CRLM was possible to treat with curative intent, yielding high survival rates. More intense follow-up after colorectal cancer resection might be of value in high-risk patients.

High Infiltration of CD203c+ Mast Cells Reflects Immunosuppression and Hinders Prognostic Benefit in Stage II-III Colorectal Cancer.

Activated mast cells (AMCs) have been fully researched in inflammation and allergic reactions. However, the protumoral role of AMCs and their biomarker CD203c has not yet been investigated in colorectal cancer (CRC). We retrospectively collected 449 postoperative patients with stage II-III CRC at two different hospitals as the training (n=310) and validation (n=139) cohorts. These findings were further validated in the independent cohort (Integration of GSE39582 and GSE17536, n=489). The AMC density was assessed using CD203c staining or the CIBERSORT method. The main analysis wasrecurrence-free survival (RFS) and overall survival (OS). As an independent factor, high AMC infiltration was associated with worse RFS/OS in the training (hazard ratio [HR]=3.437/3.014, all p<0.001) and validation (HR=3.537/2.382, all p<0.001) cohorts. We developed and validated an AMC-based nomogram for better stratification for postoperative recurrence in these two cohorts. The role of AMC density was further validated in the independent cohort. High AMC infiltration was associated with decreased RFS/OS after adjuvant chemotherapy (all p<0.05). Approximately 74.2% of intramural CD203c+ AMCs expressed a high level of PD-L1. Multiple immunosuppressive pathways were enriched in high AMC infiltration tumors, including upregulation of the TNF-α/NF-κB and angiogenesis pathways and downregulation of the IFN-γ and IFN-α responses. AMC infiltration was reversely associated with CD8+ T-cell infiltration (all p<0.05). High AMC infiltration is associated with worse survival outcomes in stages II-III CRC. AMC density may serve as a potential biomarker for survival benefit in patients receiving adjuvant chemotherapy. This AMC-based nomogram could provide better recurrence stratification. Immunosuppression in tumors with high AMC infiltration might contribute to promoting tumor progression.

Patient-Reported Symptom Burden and Supportive Care Needs of Patients With Stage II-III Colorectal Cancer During and After Adjuvant Systemic Treatment: A Real-World Evidence Study.

Patients with colorectal cancer (CRC) experience a range of physical and psychologic symptoms, and supportive care needs throughout the illness trajectory. We used patient-reported outcomes and administrative health data to describe symptom burden and supportive care needs during and after adjuvant treatment and determine factors associated with changes to symptom burden. A retrospective population-based cohort study of patients who were newly diagnosed with stage II-III CRC in Alberta, Canada, between January 1, 2016, and January 31, 2019. Adults age 18 years or older who completed a patient-reported outcomes survey (Edmonton Symptom Assessment System) and supportive care needs (Canadian Problem Checklist) within 3 months after starting adjuvant treatment (during treatment) and > 7 months after starting treatment (after treatment) were included. Changes to symptom severity were stratified as stable, improved, or deteriorated. Multivariable logistic regression was used to evaluate factors associated with these changes. We included 303 patients (median age 60 years, 62% male, 84.5% stage III, 51.2% rectal v colon). Prevalent symptoms included tiredness (80.5%), pain (50.8%), and poor well-being (50%) during treatment, and tiredness (71.3%), pain (44.2%), and poor well-being (62.1%) after treatment. The results were heterogeneous with respect to improvements, stability, or deterioration. Pain worsened for 25% of the cohort, tiredness for 28%, and depression, anxiety, and well-being for 21%, 22%, and 31%, respectively. Deterioration of some symptoms was associated with older age, stage II, comorbidities, rural setting, and higher income. We demonstrated symptom severity was generally low and most symptoms remained stable or improved after treatment. Particular groups of patients were at greater risk for more severe and/or more persistent symptoms. Ongoing assessments and interventions to address physical and psychologic symptoms, and supportive care needs in patients with CRC during and after treatment are needed.

Identification of Prognostic Gene Signatures by Developing a scRNA-Seq-Based Integration Approach to Predict Recurrence and Chemotherapy Benefit in Stage II-III Colorectal Cancer.

Prospective identification of robust biomarkers related to prognosis and adjuvant chemotherapy has become a necessary and critical step to predict the benefits of adjuvant therapy for patients with stage II–III colorectal cancer (CRC) before clinical treatment. We proposed a single-cell-based prognostic biomarker recognition approach to identify and construct CRC up- and down-regulated prognostic signatures (CUPsig and CDPsig) by integrating scRNA-seq and bulk datasets. We found that most genes in CUPsig and CDPsig were known disease genes, and they had good prognostic abilities in CRC validation datasets. Multivariate analysis confirmed that they were two independent prognostic factors of disease-free survival (DFS). Significantly, CUPsig and CDPsig could effectively predict adjuvant chemotherapy benefits in drug-treated validation datasets. Additionally, they also performed well in patients with CMS4 subtype. Subsequent analysis of drug sensitivity showed that expressions of these two signatures were significantly associated with the sensitivities of CRC cell lines to multiple drugs. In summary, we proposed a novel prognostic biomarker identification approach, which could be used to identify novel prognostic markers for stage II–III CRC patients who will undergo adjuvant chemotherapy and facilitate their further personalized treatments.

331P Predicting outcomes following colorectal cancer resection: Using real-world data to empower adjuvant treatment decision making

Guidelines advocate adjuvant therapy for selected patients with resected stage II-III colorectal cancer. Risks however remain poorly defined. ESMO guidelines describe 5-year survival after resection alone of 68-83% for stage II and 45-65% for stage III; rates can be improved by 3-5% in high-risk stage II colon cancer and 10-15% in stage III with 5FU, and a further 4-5% with oxaliplatin. These windows are wide and do not take many patient factors into account. Informed decision making with discussion of the risk to benefit ratio of chemotherapy is paramount. Grade 3-4 toxicities can occur in as many as 25-55% of patients, depending on regimen and duration of treatment. Such wide ranges make balancing potential benefit and risk very challenging. In breast cancer, the widely used PREDICT online tool allows clinicians and patients to quantitively evaluate risk in a simple and user-friendly manner. There is a clear need for a similar tool in GI oncology. The CORECT-R database is a curated, linked dataset of over 600,000 patients with colorectal cancer in England. Data is available on patient and tumour characteristics, treatments and outcomes. Using overall survival as our primary outcome we performed Cox proportional hazards modelling to compare patients receiving chemotherapy with those who did not. Multivariate modelling including both patient factors, such as age and frailty, and tumour factors, such as staging information, was used. A prototype web interface to view these data was built. We present a prototype web-based tool to predict the benefits of adjuvant chemotherapy, with appropriate confidence intervals, based on a large dataset of real-world data. Quantitative, user-friendly tools such as PREDICT are invaluable for empowering patients to make informed decisions regarding adjuvant treatment. Here we use real-world data at unprecedented scale to provide a proof-of-concept tool for colorectal cancer. Following further validation, this could be transformative for adjuvant treatment decision making.

Irregular delay of adjuvant chemotherapy correlated with poor outcome in stage II-III colorectal cancer

AimsAdjuvant chemotherapy (ACT) plays an important role in improving the survival of stage II-III colorectal cancer (CRC) patients after curative surgery. However, the prognostic role of irregular delay of ACT (IDacT) for these patients has been less studied.Materials and methodsA total of 117 stage II-III CRC patients who underwent radical resection and received at least 3 months ACT were enrolled retrospectively. The significance of IDacT, including total delay (TD) and delay per cycle (DpC), in predicting disease-free survival (DFS) was determined using receiver operating characteristic curve (ROC) analysis. The survival differences between the TD, DpC-short and DpC-long subgroups were tested using Kaplan–Meier analysis, and risk factors for prognosis were determined using a Cox proportional hazards model.ResultsUsing 35.50 and 3.27 days as the optimal cut-off points for TD and DpC, respectively, ROC analysis revealed that TD and DpC had sensitivities of 43.60% and 59.00% and specificities of 83.30% and 62.80%, respectively, in predicting DFS (both P < 0.05). No differences in the clinicopathological parameters were found between the TD, DpC-short or -long subgroups except histological differentiation in different TD subgroups and combined T stages in different DpC subgroups (both P = 0.04). Patients in the TD or DpC-long group exhibited significantly worse survival than in the -short group (TD: Log rank = 9.11, P < 0.01; DpC: Log rank = 6.09, P = 0.01). DpC was an independent risk factor for prognosis (HR = 2.54, 95% CI: 1.32–4.88, P = 0.01).ConclusionsIDacT had a profound effect on the outcome for stage II-III CRC. Although TD and DpC were significant for the prognosis, DpC was more robust, and patients who presented DpC for a long time had a significantly worse DFS.

Clinical impact of primary tumor sidedness and sex on unresectable post-recurrence survival in resected pathological stage II-III colorectal cancers: a nationwide multicenter retrospective study

BackgroundSeveral studies have demonstrated that right-sided tumors have poorer prognosis than left-sided tumors in patients with unresectable colorectal cancer (CRC). The predictive ability of the tumor sidedness in CRC treated with chemotherapy in each sex is unclear.MethodsSubjects were 964 unresectable recurrent patients treated with chemotherapy with stage II-III CRC after curative resection between 2004 and 2012. Post-recurrence cancer-specific survival (CSS) for each sex was examined.ResultsPatients were 603 males (222 right-side tumors (cecum to transverse colon) and 381 left-sided tumors (descending colon to rectum)), and 361 females (167 right-side tumors and 194 left-sided tumors). Right-sided tumors developed peritoneal recurrences in males and females. Left-sided tumors were associated with locoregional recurrences in males and with lung recurrences in females. Right-sided tumors were associated with shorter post-recurrence CSS in both sexes. In males, multivariate analyses showed that right-sided tumors were associated with shorter post-recurrence CSS (HR: 1.53, P < 0.0001) together with the presence of regional lymph node metastasis histopathological type of other than differentiated adenocarcinoma, the recurrence of liver only, the recurrence of peritoneal dissemination only, and relapse-free interval less than one-year. In females, multivariate analyses showed that right-sided tumors were associated with shorter post-recurrence CSS (HR: 1.50, P = 0.0019) together with advanced depth of invasion, the presence of regional lymph node metastasis, and recurrence of liver only.ConclusionsPrimary tumor sidedness in both sexes in unresectable recurrent CRC patients treated with chemotherapy may have prognostic implications for post-recurrence CSS.

Application of Prognostic Models Based on Psoas Muscle Index, Stage, Pathological Grade, and Preoperative Carcinoembryonic Antigen Level in Stage II-III Colorectal Cancer Patients Undergoing Adjuvant Chemotherapy.

Objective To investigate the effect of sarcopenia on the prognosis of stage II-III colorectal cancer patients undergoing adjuvant chemotherapy. Methods A total of 196 stage II-III colorectal cancer patients who received 8 cycles of postoperative chemotherapy were retrospectively analyzed. An abdominal CT acquired at 3-4 weeks after surgery was used to calculate the psoas muscle index. Subsequently, once gender-specific receiver operating characteristic curves were plotted and cut-off values of psoas muscle index were defined, the clinicopathological characteristics and the prognosis of patients with high and low values were compared. Lastly, prognostic models were established based on the independent prognostic factors of relapse-free survival and overall survival identified by COX analysis. Results Based on the psoas muscle index, the prevalence of sarcopenia was 37.5% among 196 patients. This prevalence has significant correlation with patients' age and gender. However, it was not related to the AJCC stage, T stage, lymph node metastasis, pathological grade, grade III-IV myelosuppression, or preoperative carcinoembryonic antigen level. In addition, both the relapse-free and the overall survival of patients with low and high psoas muscle indexes were significantly different. COX analysis indicated that the psoas muscle index was an independent prognostic factor. Both the overall survival prognostic model based on patients' psoas muscle index, stage, pathological grade, and preoperative carcinoembryonic antigen level and the relapse-free survival prognostic model based on patients' psoas muscle index, pathological grade, and preoperative carcinoembryonic antigen level could accurately predict the prognosis of patients. Conclusion For stage II-III colorectal cancer patients, the presence of sarcopenia before adjuvant chemotherapy would adversely affect their recurrence-free and overall survival. Prognostic models based on psoas muscle index, stage, pathological grade, and preoperative carcinoembryonic antigen level could accurately predict the prognosis in these patients.

LncRNA PCAT1 might coordinate ZNF217 to promote CRC adhesion and invasion through regulating MTA2/MTA3/Snai1/E-cadherin signaling.

LncRNA prostate cancer-associated transcript 1 (PCAT1) is a well-known oncogene, but the mechanisms of exosomes PCAT1 in colorectal cancer (CRC) remain largely unknown. Thus, the mechanisms of exosomes lncRNA PCAT1 were investigated. The expressions of exosomes lncRNA PCAT1 in tissues from stage 0-I and stage II-III CRC patients, and intestinal epithelial cell line FHC and two CRC cell lines, HT29 and HCT8 were measured by real-time quantitative PCR. The effects of lncRNA PCAT1 on adhesion and invasion of two CRC cell lines were investigated by cell-matrix adhesion and transwell assays. In addition, the target of PCAT1 (ZNF217) was validated using an RNA immune precipitation assay. Finally, the protein levels of MTA2, MTA3, SNAI1, and E-cadherin in normal participants, stage 0-I and stage II-III CRC patients, as well as two cell lines with stable ZNF217 knockdown were investigated by western blotting. The plasma exosomal lncRNA PCAT1 was found to be significantly increased in the CRC tissues and cell lines. In addition, lncRNA PCAT1 knockdown significantly inhibited the adhesion and invasion of HT29 and HCT8 cells. RIP assay results showed lncRNA PCAT1 could target ZNF217, and downregulation of lncRNA PCAT1 could decrease the protein expressions of ZNF217 in two CRC cells lines. Moreover, ZNF217 knockdown significantly decreased MTA2, MTA3, and SNAI1 expressions, but increased E-cadherin expressions in both CRC cells lines. Exosomal lncRNA PCAT1 can promote the adhesion and invasion of CRC cells, and PCAT1 overexpression may lead to ZNF217 upregulation that regulates EMT-related MTA2/MTA3/Snai1/E-cadherin signaling.

Three Macrophage-Based Subgroups for Predicting Treatment Relapse in Stage II-III Colorectal Cancer. An Integrated Analysis of CD86+ and CD206+ Macrophages

Three Macrophage-Based Subgroups for Predicting Treatment Relapse in Stage II-III Colorectal Cancer. An Integrated Analysis of CD86+ and CD206+ Macrophages

The Ratio of CD86+/CD163+ Macrophages Predicts Postoperative Recurrence in Stage II-III Colorectal Cancer.

Tumor-associated macrophages (TAMs) are pivotal for tumor progression and metastasis. We investigated the stromal CD86+TAM/CD163+TAM (CD86/CD163) ratio as a novel prognostic biomarker for stage II-III colorectal cancer (CRC). Two independently clinical cohorts of stage II-III CRC were retrospectively enrolled in this study. TAMs were detected using immunohistochemical staining for CD86 and CD163. The stromal CD86/CD163 ratio was calculated as a prognostic biomarker for recurrence-free survival (RFS) and overall survival (OS). Patients with a low CD86/CD163 ratio had shorter RFS (HR=0.193, p<0.001) and OS (HR=0.180, p<0.001) than patients with a high CD86/CD163 ratio in the training cohort. CD86/CD163 ratio may be an independent predictor for RFS (HR=0.233, p<0.001) and OS (HR=0.224, p<0.001) in the training cohort. We obtained equivalent results in the validation cohort. The CD86/CD163 ratio tends to have better predictive values than tumor stage in the training (AUC: 0.682 vs 0.654, p=0.538) and validation (AUC: 0.697 vs 0.659, p=0.586) cohorts. CD86/CD163 ratio effectively predicts RFS for stage II (HR=0.203, p<0.001) and stage III CRC (HR=0.302, p<0.001). CD86/CD163 ratio also effectively predicts RFS in CRC patients with adjutant chemotherapy (HR=0.258, p<0.001) and without adjutant chemotherapy (HR=0.205, p<0.001). The stromal CD86/CD163 ratio could be used for individual risk assessment of recurrence and mortality for stage II-III CRC. Together with tumor stage, this ratio will aid in the personal treatment.