Resection For Colorectal Cancer Research Articles

Improving risk models for patients having emergency bowel cancer surgery using linked electronic health records: a national cohort study.

Life-saving emergency major resection of colorectal cancer (CRC) is a high-risk procedure. Accurate prediction of postoperative mortality for patients undergoing this procedure is essential for both healthcare performance monitoring and preoperative risk assessment. Risk-adjustment models for CRC patients often include patient and tumour characteristics, widely available in cancer registries and audits. The authors investigated to what extent inclusion of additional physiological and surgical measures, available through linkage or additional data collection, improves accuracy of risk models. Linked, routinely-collected data on patients undergoing emergency CRC surgery in England between December 2016 and November 2019 were used to develop a risk model for 90-day mortality. Backwards selection identified a 'selected model' of physiological and surgical measures in addition to patient and tumour characteristics. Model performance was assessed compared to a 'basic model' including only patient and tumour characteristics. Missing data was multiply imputed. Eight hundred forty-six of 10578 (8.0%) patients died within 90 days of surgery. The selected model included seven preoperative physiological and surgical measures (pulse rate, systolic blood pressure, breathlessness, sodium, urea, albumin, and predicted peritoneal soiling), in addition to the 10 patient and tumour characteristics in the basic model (calendar year of surgery, age, sex, ASA grade, TNM T stage, TNM N stage, TNM M stage, cancer site, number of comorbidities, and emergency admission). The selected model had considerably better discrimination compared to the basic model (C-statistic: 0.824 versus 0.783, respectively). Linkage of disease-specific and treatment-specific datasets allowed the inclusion of physiological and surgical measures in a risk model alongside patient and tumour characteristics, which improves the accuracy of the prediction of the mortality risk for CRC patients having emergency surgery. This improvement will allow more accurate performance monitoring of healthcare providers and enhance clinical care planning.

Clinical effect of laparoscopic radical resection of colorectal cancer based on propensity score matching.

The incidence of colorectal cancer (CRC) is increasing annually. Laparoscopic radical resection of CRC is a minimally invasive procedure preferred in clinical practice. To investigate the clinical effect of laparoscopic radical resection of CRC on the basis of propensity score matching (PSM). The clinical data of 100 patients who received inpatient treatment for CRC at Changde Hospital, Xiangya School of Medicine, Central South University (The First People's Hospital of Changde City) were analyzed retrospectively. The control group included patients who underwent open surgery (n = 43), and those who underwent laparoscopic surgery formed the observation group (n = 57). The baseline information of both groups was equipoised using 1 × 1 PSM. Differences in the perioperative parameters, inflammatory response, immune function, degree of pain, and physical status between the groups were analyzed. Thirty patients from both groups were successfully matched. After PSM, baseline data showed no statistically significant differences between the groups: (1) Perioperative parameters: The observation group had a longer surgery time, less intraoperative blood loss, earlier first ambulation and first anal exhaust times, and shorter gastric tube indwelling time than the control group; (2) Inflammatory response: 24 h after surgery, the levels of interleukin-6 (IL-6), C-reactive protein (CRP), and tumor necrosis factor-α (TNF-α) between groups were higher than preoperatively. IL-6, CRP, and TNF-α levels in the observation group were lower than in the control group; (3) Immune function: At 24 h after surgery, counts of CD4-positive T-lymphocytes (CD4+) and CD4+/CD8-positive T-lymphocytes (CD8+) in both groups were lower than those before surgery, whereas CD8+ was higher than that before surgery. At 24 h after surgery, both CD4+ counts and CD4+/CD8+ in the observation group were higher than those in the control group, whereas CD8+ counts were lower; (4) Degree of pain: The visual analog scale scores in the observation group were lower than those in the control group at 24 and 72 h after surgery; and (5) Physical status: One month after surgery, the Karnofsky performance score in the observation group was higher than that in the control group. Laparoscopic radical resection of CRC has significant benefits, such as reducing postoperative pain and postoperative inflammatory response, avoiding excessive immune inhibition, and contributing to postoperative recovery.

Oncological features and prognosis of colorectal cancer in human immunodeficiency virus-positive patients: A retrospective study.

Due to the prolonged life expectancy and increased risk of colorectal cancer (CRC) among patients with human immunodeficiency virus (HIV) infection, the prognosis and pathological features of CRC in HIV-positive patients require examination. To compare the differences in oncological features, surgical safety, and prognosis between patients with and without HIV infection who have CRC at the same tumor stage and site. In this retrospective study, we collected data from HIV-positive and -negative patients who underwent radical resection for CRC. Using random stratified sampling, 24 HIV-positive and 363 HIV-negative patients with colorectal adenocarcinoma after radical resection were selected. Using propensity score matching, we selected 72 patients, matched 1:2 (HIV-positive:negative = 24:48). Differences in basic characteristics, HIV acquisition, perioperative serological indicators, surgical safety, oncological features, and long-term prognosis were compared between the two groups. Fewer patients with HIV infection underwent chemotherapy compared to patients without. HIV-positive patients had fewer preoperative and postoperative leukocytes, fewer preoperative lymphocytes, lower carcinoembryonic antigen levels, more intraoperative blood loss, more metastatic lymph nodes, higher node stage, higher tumor node metastasis stage, shorter overall survival, and shorter progression-free survival compared to patients who were HIV-negative. Compared with CRC patients who are HIV-negative, patients with HIV infection have more metastatic lymph nodes and worse long-term survival after surgery. Standard treatment options for HIV-positive patients with CRC should be explored.

Normal CEA Levels After Neoadjuvant Chemotherapy and Cytoreduction with Hyperthermic Intraperitoneal Chemoperfusion Predict Improved Survival from Colorectal Peritoneal Metastases.

Normal carcinoembryonic antigen (CEA) levels (≤ 2.5 ng/ml) after resection of localized colorectal cancer or liver metastases are associated with improved survival, however, these trends are understudied for colorectal peritoneal metastases (CRPM). We conducted a retrospective single-institution study of patients with CRPM undergoing cytoreductive surgery with hyperthermic intraperitoneal chemoperfusion (CRS/HIPEC) with and without neoadjuvant chemotherapy (NACT). CEA was measured before and after NACT and within 3 months after CRS/HIPEC. A total of 253 patients (mean age 55.3 years) with CRPM undergoing CRS/HIPEC had complete CEA data and 191 also underwent NACT with complete data. The median peritoneal carcinomatosis index score (PCI) of the overall cohort was 12 and 82.7% of patients had complete cytoreduction (CC0). In total, 64 (33.5%) patients had normal CEA levels after NACT with a median overall survival (OS) of 45.2 months compared with those with an elevated CEA (26.4 months, p = 0.004). Patients with normal CEA after NACT had a lower PCI found at the time of surgery than those with elevated CEA (10 versus 14, p < 0.001), 68 (26.9%) patients with an elevated preoperative CEA level experienced normalization after CRS/HIPEC, and 118 (46.6%) patients had elevated CEA after CRS/HIPEC. Patients who experienced normalization demonstrated similar OS to patients that had normal CEA levels pre- and post-surgery and improved OS compared with those with elevated postop CEA (median 41.9 versus 47 months versus 17.1 months, respectively, p < 0.001). Normal CEA levels after NACT and/or CRS/HIPEC are associated with improved survival for patients with CRPM. Patients that normalize CEA levels after surgery have similar survival to those with normal preoperative levels.

P1171 The impact of biological and small molecule therapy on time to colonic resection and cancer rates in patients with Ulcerative Colitis

Abstract Background The expanding medical armamentarium in ulcerative colitis (UC) has contributed to increased control of inflammation. However, simultaneously, postponed colonic resection with an accumulative inflammatory burden might lead to an increased risk of CRC. Recent studies have reported conflicting results regarding the incidence of colorectal cancer (CRC) in UC patients. Aim To analyse the impact of advanced medical therapies (defined as biologicals and small molecules) on time to colonic resection and risk of CRC in UC patients. Methods Consecutive patients ≥18 years with established UC who underwent colonic resection between January 2003 and October 2022 at the Academic Medical Centre Amsterdam or the University Hospital Leuven were included. Primary outcomes were time to colonic resection and CRC rate in colonic specimens, compared between four time periods: P1 (2003-2007), P2 (2008-2012), P3 (2013-2017) and P4 (2018-2022). Secondary outcomes were the effect of advanced medical therapy on time to resection, cancer stage and risk of CRC. CRC was staged according to the AJCC TNM classification (advanced cancer defined as T3/T4, N1/2 or M1). Results A total of 716 patients were included. The usage of advanced medical therapies prior to surgery increased from 38.2% in P1 to 90.2% in P4 (p&amp;lt;0.001). However, this did not result in an increased time to colonic resection (P1: 7 years (2-12) vs P2: 6 years (2-14) vs P3: 7 years (3-14) vs P4: 7 years (2-14), p=0.94). CRC was diagnosed in 72 (10.1%) patients, and this incidence did also not change over time. Time to resection was significantly longer (median 18 years, IQR 10-24) in CRC patients compared to the overall cohort. The majority of CRC patients (64.8%) were diagnosed with advanced cancer, which did not decrease over time. Patients using advanced medical therapies had significantly shorter follow-up compared to therapy-naïve patients (6 years vs. 10 years, p&amp;lt;0.001), which resulted in a decreased risk of CRC (OR 0.17, p=&amp;lt;0.001). However, the finding of an incidental carcinoma rate (i.e. not preoperatively diagnosed) in this group was 18% whereas this was only 4% in patients without advanced medical therapy (p=0.08). Moreover, the incidence of advanced CRC was numerically higher in UC patients who received ≥2 therapies (83.3% vs 61.0%, p=0.14). Conclusion This study demonstrated that in the last two decades, the increased usage of advanced medical therapies did not result in an increased time to resection, nor in a decreased CRC rate in UC patients undergoing colonic resection. A higher incidence of incidental and advanced cancers was seen in patients with ≥2 therapies. Therefore, care should be taken with improved tailored surveillance in this group.

National analysis of racial disparities in emergent surgery for colorectal cancer

BackgroundRacial disparities in access to preoperative evaluation for colorectal cancer remain unclear. Emergent admission may indicate lack of access to timely care. The present work aimed to evaluate the association of admission type with race among patients undergoing colorectal cancer surgery. MethodsAll adults undergoing resection for colorectal cancer in 2011–2020 National Inpatient Sample were identified. Multivariable regression models were developed to examine the association of admission type with race. Primary outcome was major adverse events (MAE), including mortality and complications. Secondary outcomes included costs and length of stay (LOS). Interaction terms between year, admission type, and race were used to analyze trends. ResultsOf 722,736 patients, 67.6 % had Elective and 32.4 % Emergent admission. Black (AOR 1.38 [95 % CI 1.33–1.44]), Hispanic (1.45 [1.38–1.53]), and Asian/Pacific Islander or Native American (1.25 [1.18–1.32]) race were associated with significantly increased odds of Emergent operation relative to White. Over the study period, non-White patients consistently comprised over 5 % greater proportion of the Emergent cohort compared to Elective. Furthermore, Emergent admission was associated with 3-fold increase in mortality and complications, 5-day increment in LOS, and $10,100 increase in costs. MAE rates among Emergent patients remained greater than Elective with a widening gap over time. Non-White patients experienced significantly increased MAE regardless of admission type. ConclusionNon-White race was associated with increased odds of emergent colorectal cancer resection. Given the persistent disparity over the past decade, systematic approaches to alleviate racial inequities in colorectal cancer screening and improve access to timely surgical treatment are warranted.

Japanese Society of Medical Oncology clinical guidelines: Molecular testing for colorectal cancer treatment, 5th edition.

Molecular testing to determine optimal therapies is essential for managing patients with colorectal cancer (CRC). In October 2022, the Japanese Society of Medical Oncology published the 5th edition of the Molecular Testing Guideline for Colorectal Cancer Treatment. In this guideline, in patients with unresectable CRC, RAS/BRAF V600E mutational and mismatch repair tests are strongly recommended prior to first-line chemotherapy to select optimal first- and second-line therapies. In addition, HER2 testing is strongly recommended because the pertuzumab plus trastuzumab combination is insured after fluoropyrimidine, oxaliplatin, and irinotecan in Japan. Circulating tumor DNA (ctDNA)-based RAS testing is also strongly recommended to assess the indications for the readministration of anti-EGFR antibodies. Both tissue- and ctDNA-based comprehensive genomic profiling tests are strongly recommended to assess the indications for targeted molecular drugs, although they are currently insured in patients with disease progression after receiving standard chemotherapy (or in whom disease progression is expected in the near future). Mutational and mismatch repair testing is strongly recommended for patients with resectable CRC, and RAS/BRAF V600E mutation testing is recommended to estimate the risk of recurrence. Mutational and mismatch repair and BRAF testing are also strongly recommended for screening for Lynch syndrome. Circulating tumor DNA-based minimal residual disease (MRD) testing is strongly recommended for estimating the risk of recurrence based on clinical evidence, although MRD testing was not approved in Japan at the time of the publication of this guideline.

Association of county-level food deserts and food swamps on postoperative outcomes among patients undergoing colorectal surgery

Although malnutrition has been linked to worse healthcare outcomes, the broader context of food environments has not been examined relative to surgical outcomes. We sought to define the impact of food environment on postoperative outcomes of patients undergoing resection for colorectal cancer (CRC). Patients who underwent surgery for CRC between 2014 and 2020 were identified from the Medicare database. Patient-level data were linked to the United States Department of Agriculture data on food environment. Multivariable regression was used to examine the association between food environment and the likelihood of achieving a textbook outcome (TO). TO was defined as the absence of an extended length of stay (≥75th percentile), postoperative complications, readmission, and mortality within 90 days. A total of 260,813 patients from 3017 counties were included in the study. Patients from unhealthy food environments were more likely to be Black, have a higher Charlson Comorbidity Index, and reside in areas with higher social vulnerability (all P<.01). Patients residing in unhealthy food environments were less likely to achieve a TO than that of patients residing in the healthiest food environments (food swamp: 48.8% vs 52.4%; food desert: 47.9% vs 53.7%; P<.05). On multivariable analysis, individuals residing in the unhealthy food environments had lower odds of achieving a TO than those of patients living in the healthiest food environments (food swamp: OR, 0.86; 95% CI, 0.83-0.90; food desert: OR, 0.79; 95% CI, 0.76-0.82); P<.05). The surrounding food environment of patients may serve as a modifiable sociodemographic risk factor that contributes to disparities in postoperative CRC outcomes.

Mortality and morbidity after colorectal cancer resection surgery in elderly patients: a retrospective population-based study in Sweden.

Colorectal cancer is primarily a condition of older adults, and surgery is the cornerstone of treatment. As life expectancy is increasing and surgical techniques and perioperative care are developing, curative surgery is often conducted even in ageing populations. However, the risk of morbidity, functional decline, and mortality following colorectal cancer resection surgery are known to increase with increasing age. This study aims to describe real-world data about postoperative mortality and morbidity after resection surgery for colorectal cancer in the elderly (≥ 70years) compared to younger patients (< 70years), in a Swedish setting. A cohort study including all patients diagnosed with colorectal cancer in a Swedish region of 1.7 million inhabitants between January 2016 and May 2020. Patients were identified through the Swedish Colorectal Cancer Registry, and all baseline and outcome variables were extracted from the registry. The following outcome measures were compared between the two age groups: 90-day mortality rates, postoperative complications, postoperative intensive care, reoperations, readmissions, and 1-year mortality. To adjust the analyses for baseline confounders in the comparison of the outcome variables, the following methods were used: marginal matching, calliper (ID matching), and logistic regression adjusted for baseline confounders. The cohort consisted of 5246 patients, of which 3849 (73%) underwent resection surgery. Patients that underwent resection surgery were significantly younger than those who did not (mean ± SD, 70.9 ± 11.4years vs 73.7 ± 12.8years, p < 0.001). Multivariable analyses revealed that both 90-day and 1-year mortality rates were higher in older patients that underwent resection surgery (90-day mortality OR 2.12 [95% CI 1.26-3.59], p < 0.005). However, there were no significant differences in postoperative intensive care, postoperative complications, reoperations, or readmissions. Elderly patients suffer increased postoperative mortality after resection surgery for colorectal cancer compared to younger individuals. Given the growing elderly population that will continue to require surgery for colorectal cancer, more efficient ways of determining and handling individual risk for older adults need to be implemented in clinical practice.

Peritoneal lavage cytology in patients with curative resection for stage II and III colorectal cancer: A multi-institutional prospective study.

11 Background: Although various prognostic factors in patients with colorectal cancer has been reported, the usefulness of intraoperative lavage cytology in patients with colorectal cancer is controversial. The aim of this study was to clarify the usefulness of intraoperative lavage cytology in patients with curative resection for pSage II-III colorectal cancer in a prospective multicenter study. Methods: The 20 member hospitals of the Japanese Society for the Cancer of the Colon and Rectum prospectively registered the patients diagnosed as stage II or III colorectal cancer preoperatively between 2013 and 2017. Among these patients, pStage II-III patients went through analysis. Lavage cytology was performed twice during surgery. The first procedure was performed right after laparotomy, and the second was performed right after specimen retrieval. The primary endpoint of this study was an effect of lavage cytology on 5-year relapse-free survival (RFS) in patients with pStage II-III colorectal cancer. The secondary endpoint was an effect of lavage cytology on 5-year overall survival (OS) and peritoneal recurrence in patients with pStage II-III colorectal cancer. Results: A total of 1378 patients were eligible and went through analysis. The number of patients with pStage II and III colorectal cancer were 670 and 708, respectively. Among 1378 patients, 54 (3.9%) had positive cytology. The median follow-up period of the entire cohort was 5.3 years. In pStage II patients, the 5-year RFS rate with positive and negative cytology was 61.1% and 81.6%, respectively (P = 0.023). The 5-year OS rate of pStage II patients with positive and negative cytology was 67.1% and 91.7%, respectively (P = 0.0083). However, there was no difference in RFS and OS between patients with positive and negative cytology in pStage III patients. Thirty-three patients had peritoneal recurrence. The peritoneal recurrence rate was 11.8% and 1.5% in pStage II patients with positive and negative lavage cytology, respectively (P = 0.032). That was 10.5% and 2.5% in pStage III patients with positive and negative lavage cytology, respectively (P = 0.022). In total, 11.1% of patients with positive lavage cytology had peritoneal recurrence in this cohort. Conclusions: The pStage II colorectal cancer patients with negative cytology had better RFS and OS compared to those with positive cytology. Peritoneal lavage cytology was useful in predicting peritoneal recurrence after curative resection for pStage II-III colorectal cancer. Clinical trial information: UMIN000026070 .

Surveillance of resected metastatic colorectal cancer utilizing circulating DNA.

214 Background: There is limited data to guide surveillance in patients with metastatic colorectal cancer (CRC) who have had curative resection using circulating tumor DNA (ctDNA) in addition to labs and imaging studies. Minimal residual disease (MRD) assays utilize circulating tumor DNA (ctDNA) for the purposes of monitoring for early recurrence and predicting therapeutic response. In this study, we aim to investigate the utility of ctDNA monitoring in the setting of resected metastatic CRC. Methods: Patients were identified through retrospective search at a tertiary care and several satellite settings to identify patients with metastatic CRC who had undergone curative resection and later had ctDNA monitoring (using Signatera assay). IRB approval was obtained for the study. We recorded demographic information (sex, race, age at diagnosis), disease characteristics (stage at diagnosis, site of primary cancer, site of metastasis), treatment regimens, clinical outcomes (recurrence, survival) and follow-up data. Our primary outcome was to evaluate the rate of recurrence in patients with metastatic CRC who had curative resection in two different population, ctDNA positive or ctDNA negative, post-surgery. Results: We identified 35 patients with a median age of 55 years (range 31 – 82) at the time of metastatic diagnosis. In this study cohort, 20 (57%) were female; 23 (66%) were white, and 10 (29%) were African American. 22 (63%) patients had left-sided primary tumors and the remaining (47%) had right-sided primary tumors. At the time of presentation, 23 (66%) patients had synchronous metastases and 12 (34%) developed metachronous metastases. ctDNA positivity was reported in 21 (60%) pts post-curative therapy. Median time from curative therapy to ctDNA positivity was 62 days. 22 (63%) pts experienced recurrence of disease post-curative resection. Median time to recurrence after ctDNA test was first positive was 6.6 months. Among 21 patients in ctDNA positive group, 19 (86%) developed recurrences and among 14 ctDNA negative patients, only 3 (21%) developed recurrences (p-value &lt;0.01). Recurrence free survival was significantly shorter in patients who were ctDNA positive post surgery (Median RFS: 7.17 months, 95% CI: 4.4-18.0 months) compared to those who were ctDNA negative (Median RFS: 30.8 months; 95% CI: 12.6-NR) (p-value=0.005). Conclusions: In patients with metastatic CRC who underwent curative resection ctDNA may have utility in predicting disease recurrence at both academic and community sites. Larger studies are needed for validation of ctDNA as an adjunct test for surveillance in broader population.

Redefining the prognostic significance of RAS and BRAF V600E mutations on disease free survival in patients with colorectal cancer in the era of ct-DNA defined minimal residual disease: Results from the MD Anderson INTERCEPT Program.

196 Background: In patients (pts) with resected colorectal cancer (CRC), circulating tumor DNA (ctDNA) is an emerging tool for the detection of minimal residual disease (MRD) following the completion of curative intent therapy. The presence of MRD is highly prognostic, with MRD+ pts having worse disease-free survival (DFS). Prior to the advent of ctDNA, the modest negative prognostic implications of BRAF and RAS mutations (mt) on DFS were established in some studies. However, it is unclear if these previously noted prognostic effects of RAS/BRAF mts will be maintained with the information provided with ctDNA testing for MRD. Methods: As part of the INTERCEPT program, pts with Stage II-IV CRC treated with curative intent at MD Anderson Cancer Center were evaluated with a tissue-informed ctDNA assay (Signatera). This ctDNA testing was performed along with routine surveillance visits (post-operatively and Q3 months). A cohort of patients from the INTERCEPT program also had correlative analysis performed including whole exome sequencing called by GATK-Mutect2 to assess for BRAFV600E and RAS mt. Results: Within the INTERCEPT program, 265 pts had whole exome sequencing and were included for this analysis, with RAS mutations in 44% (n=116) and BRAF V600E in 3.8% (n=10). After a median follow up of 16-m, the median was DFS 7.93-m (95% CI 5.52 – 10.33-m) in ctDNA+ vs not reached in ctDNA-ve. There was no significant difference between ctDNA+ rates in RAS mt vs RAS wt pts (χ2 p=0.41); 217 pts were ctDNA-ve with a DFS HR=1.81 for RAS mut vs wt (95% CI 0.57-5.73, p=0.30). The 12-m DFS in this cohort was 95.2% in RAS mt vs 97.9% in RAS wt (OR 1.25, 95% CI 0.4-4.4, p=NS). 48 pts were ctDNA+, with no difference in DFS by RAS mt status with HR=1.42 (95% CI 0.76 – 2.64, p = NS), which was unchanged after excluding those with radiographically evident disease at or shortly after the finding of ctDNA+. In a multivariate model, after controlling for ctDNA status, there was no prognostic impact of RAS on DFS in the larger population with HR 1.51 (95% CI 0.88 – 2.60; p = NS). While the number of pts with BRAF V600E mt was low, there was no evidence of a prognostic effect after controlling for ctDNA status. Conclusions: In CRC pts treated with curative intent, positive ctDNA at any point post-operatively or during surveillance is highly predictive of disease recurrence. In these pts, RAS mt status was not associated with DFS. Moreover, RAS mt pts are not more likely to be ctDNA+ve. Thus, our data suggest that the presence of ctDNA defined MRD has greater prognostic value than the presence or absence of RAS or BRAF V600E mt.

Clinicopathologic characteristics of patients with early-onset colorectal cancer.

74 Background: Although the incidence of colorectal cancer has been declining in the United States in recent years, the incidence of young patients under 50 years of age has been reported to be increasing by several percent per year. Various studies have been conducted to characterize early-onset colorectal cancer (EO-CRC); however, it has been unclear whether it is a different entity from late-onset colorectal cancer (LO-CRC). In this study, we evaluated the clinicopathologic characteristics of EO-CRC in Japan. Methods: This study included 1,336 patients who underwent surgical resection for colorectal cancer at Tokyo Metropolitan Komagome Hospital from January 2015 to December 2019. We performed genetic testing for patients with suspected Lynch syndrome after providing genetic counseling and obtaining informed consent. The study protocol was approved by the Institutional Review Board. Results: Of the 1,336 colorectal cancer patients, 117 (8.9%) had EO-CRC with a median age at the diagnosis of 44 (17–49) years. Tumors were located at right-sided colon in 23 patients and left-sided colorectum in 92 patients with EO-CRC, respectively. The clinical stage of the tumor was I in 19, II in 23, III in 50, and IV in 23 patients with EO-CRC, respectively. Histologically, differentiated type, undifferentiated type, and mucinous carcinoma were 106, 5, and 3 patients, respectively. KRAS mutation was detected in 25.0% and BRAF V600E was detected in 4.3% of patients with EO-CRC. In the microsatellite status, MSI-High was detected in 6 (5.1%) patients with EO-CRC, of whom 3 (2.6%) were diagnosed with Lynch syndrome by genetic testing. Causative genes were MLH1 in 2 patients and MSH2 in one patient. In hereditary tumors, 2 patients with familial adenomatous polyposis were included in addition to Lynch syndrome. On the other hand, 1,219 (91.2%) had LO-CRC with 34.5% of KRAS mutation and 6.4% of BRAFV600E. MSI-High was detected in 69(5.7%) patients with LO-CRC，of whom 5 (0.4%) were diagnosed with Lynch syndrome. Lynch syndrome was significantly more common in EO-CRC (p=0.026). Conclusions: The alterations of KRAS and BRAF tended to be more frequent in EO-CRC. The frequency of hereditary CRC was more frequent in EO-CRC than in LO-CRC.

Real-world evidence of FOLFIRI combined with anti-angiogenesis inhibitors or anti-EGFR antibodies for patients with early recurrence colorectal cancer after adjuvant FOLFOX/CAPOX therapy in Japan: A retrospective observational study using administrative database.

110 Background: Oxaliplatin-containing regimens (FOLFOX or CAPOX) are the most common adjuvant treatments after curative resection of colorectal cancer (CRC). However, real-world evidence (RWE) of treatment sequence/outcomes for patients with early recurrence CRC after receiving adjuvant chemotherapy are limited. Methods: This retrospective cohort study was based on an administrative database in Japan. The primary objective was to describe the treatment sequence for patients with early recurrence CRC and treated by combination of FOLFIRI and anti-angiogenesis inhibitors (AAIs) or anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (mAbs) after adjuvant FOLFOX or CAPOX therapy. The study included patients with CRC who underwent surgical resection, started adjuvant chemotherapy ≤3 months (mo) after the first surgery, had early recurrence of CRC (defined as initiation of FOLFIRI + AAIs/anti-EGFR mAbs second line [2L] regimen) within 1 year after adjuvant chemotherapy ended. Patient characteristics at baseline of 2L (60 days prior to 2L initiation) and treatment sequence were summarized descriptively; time to discontinuation (TTD) for adjuvant and 2L therapy were analyzed using Kaplan-Meier method. Cox proportional hazard model was used to identify risk factors associated with TTD of 2L regimen. Results: The cohort included 832 patients: median (range) age was 67 (24-86) years, 56.4% males, 65.5% with left-sided CRC. Most patients received CAPOX (71.3%) as adjuvant therapy. Median (95% CI) duration of adjuvant therapy was 5.4 mo (5.3-5.5). As 2L therapy, 72.5% and 27.5% of patients received FOLFIRI + AAIs (AAIs group) and FOLFIRI + anti-EGFR mAbs (anti-EGFR group), respectively. Median TTD (95% CI) of the AAIs and anti-EGFR groups in 2L were 6.2 mo (5.8-6.9) and 6.1 mo (5.2-7.4), respectively. Among patients with recurrence within 6 mo (72.6%), the median TTD (95% CI) for AAIs and anti-EGFR groups were 6.1 mo (5.5- 6.5) and 5.8 mo (5.1-7.8), respectively. Among patients with recurrence during 6 to 12 mo (27.4%), the median TTD (95% CI) of AAIs and anti-EGFR groups were 8.1 mo (6.1-9.2) and 6.2 mo (4.6-8.0), respectively. Age ≥70 years was negatively associated with TTD of 2L, HR = 1.19 (95% CI: 1.02-1.39); p=0.03. Conclusions: This is the first RWE based on administrative data on treatment sequence/ outcomes for patients with early recurrence CRC treated by FOLFIRI + AAIs/anti-EGFR mAbs after adjuvant FOLFOX/CAPOX therapy in Japan. The treatment outcomes for patients with early recurrence CRC were similar to previous clinical trials in 2L advanced CRC. The results suggested that these two 2L regimens had similar TTD; however, the timing of relapse may influence the efficacy of AAIs and anti-EGFR mAbs.

Association of pathologic nodal status with minimal residual disease after neoadjuvant treatment and resection of locally advanced rectal cancer.

205 Background: Studies have shown that minimal residual disease (MRD) identified by detection of circulating tumor DNA (ctDNA) is associated with recurrence after surgical resection of colorectal cancer. Though multiple trials are evaluating the use of ctDNA to guide adjuvant therapy, data on the utility of ctDNA after neoadjuvant therapy is limited. In this study, we evaluated the associations between ctDNA and recurrence after neoadjuvant treatment and resection of rectal cancer (LARC). Methods: Consecutive patients with primary rectal cancer treated with neoadjuvant systemic therapy and/or chemoradiotherapy followed by resection between 12/2020-4/2023 were identified. Patients were tested for ctDNA via the MD Anderson INTERCEPT platform using a high-sensitivity patient informed assay. Patients with metastases or a first ctDNA test more than 3 months after resection were excluded. MRI-determined stage, extramural vascular invasion (mrEMVI), pelvic sidewall adenopathy (PSW), pathologic lymphovascular invasion (LVI), perineural invasion (PNI) and tumor regression grade (TRG) were collected. Associations between these factors and ctDNA status were analyzed with Fischer’s exact test. Recurrence free survival (RFS) was analyzed with the log-rank test. Results: Sixty-seven patients (3 treated with chemoradiotherapy alone, 15 with systemic therapy alone and 49 with total neoadjuvant therapy) were identified. Positive ctDNA was identified in 6 (8.9%) within 3 months after resection, all of whom received total neoadjuvant therapy, and 3/6 recurred within 12 months. Clinical T status (p=0.146), N status (p=0.842), mrEMVI (p=0.475) and PSW (p=0.318) were not associated with MRD. TRG was not associated with MRD (TRG0-1: 4% vs TRG2-3: 11.3%, p=0.547). Pathologic N status was associated with MRD (ypN0: 4.4% vs ypN+: 18%, p=0.049). MRD was associated with a median RFS of 3.2 months (HR 39, 95% CI: 4.1-380, p=0.0015). 1-year RFS was 98% for patients without MRD. Conclusions: Minimal residual disease after multi-modality treatment of LARC is associated with early metastatic recurrence. The patient informed MRD assay appears both sensitive and specific for detection of relapse. Advanced clinical stage and high-risk radiologic features were not associated with MRD, while post-treatment pathologic N status was. Given the high relapse rate for MRD+ patients, MRD detection after resection warrants additional investigation for metastases and/or enrollment on MRD treatment clinical trial. Methods to predict MRD prior to resection are urgently needed.

Abstract C092: T cell responses and clinical outcomes in pancreatic and colorectal cancer patients with minimal residual disease in AMPLIFY-201, a phase 1 trial of a first-in-class amphiphile lymph node targeted mutant KRAS vaccine

Abstract Background: Mutations in RAS occur in &amp;gt; 25% of solid tumors and &amp;gt; 90% of patients (pts) with PDAC and &amp;gt; 40% of pts with CRC. ELI-002 2P is a vaccine comprised of lymph-node targeted Amphiphile (Amph)-modified G12D and G12R mutant KRAS peptides together with an Amph-modified CpG oligonucleotide adjuvant designed to expand polyfunctional mutant KRAS-specific T cells. Interim phase 1 AMPLIFY-201 data (O’Reilly et al; ASCO, 2023, #2528) showed that adjuvant administration of ELI-002 was well-tolerated, with T cell responses in 87%, and tumor biomarker responses in 77% (a subset of 32% had ctDNA clearance). Here we report relapse free survival data and correlations between ELI-002 2P- induced T cell levels and outcomes in pts with PDAC and colorectal cancer (CRC) at high risk for relapse following locoregional treatment. Methods: Resected PDAC (n=20) and CRC (n=5) pts with tumors harboring KRAS G12D or G12R who had minimal residual disease positivity (MRD+) defined as elevated circulating tumor DNA (ctDNA) and/or serum tumor biomarker (CA19-9/CEA), received up to 6 priming doses and 4 booster doses separated by a 3-month rest period of subcutaneous ELI-002 2P vaccine monotherapy comprised of Amph-peptides (700 mcg each G12D/G12R), admixed with Amph-CpG-7909 at 0.1, 0.5, 2.5, 5.0 and 10.0 mg per cohort dose level. Primary endpoints included safety and recommended phase 2 dose (RP2D) of Amph-CPG-7909; secondary endpoints: biomarker reduction/clearance; exploratory endpoints: included relapse free survival (RFS) using immune Response Evaluation Criteria in Solid Tumors (iRECIST) and immunogenicity assessed by direct ex vivo Fluorospot and intracellular cytokine staining of peripheral blood mononuclear cells. Results: Direct ex vivo polyfunctional mKRAS-specific T cell responses to ELI-002 2P were observed in 20/23 (87%; 50% induced both CD4+ and CD8+ T cells, median 13-fold and mean 56-fold increase from baseline), with response in 9/9 (100%) pts treated at highest two dose levels including the 10 mg RP2D. Clinical efficacy correlated with T cell response in evaluable pts (n=22): median tumor biomarker reduction/clearance was -86.9% vs -4.5% in above vs below median T cell responders, respectively (p &amp;lt; 0.0124). At 25 weeks median follow-up, the median RFS was not reached compared to 17.1 weeks in above versus below median T cell responders (HR 0.11; 95% CI 0.027-0.446; p = 0.0108). The association of RFS with T cell response was not confounded by other baseline prognostic variables (including tumor stage, recovery from prior cytotoxic therapy as assessed by absolute neutrophil count, or immune system subsets such as %CD4+ or %CD8+of CD3+ lymphocytes). Conclusions: The association of ELI-002 2P vaccine T cell responses with clinical outcomes in a novel MRD+ trial design underscores the potential to reduce recurrence in the setting of microsatellite stable PDAC and CRC. A new phase 1/2 trial, AMPLIFY-7P (NCT05726864), is evaluating a new seven peptide (G12D, G12R, G12V, G12C, G12A, G12S, G13D) ELI-002 7P formulation. Citation Format: Zev A. Wainberg, Shubham Pant, Colin D. Weekes, Muhammad Furqan, Pashtoon M. Kasi, Craig E. Devoe, Alexis D. Leal, Vincent Chung, James R. Perry, Lochana Seenappa, Lisa K. McNeil, Esther Welkowsky, Peter C. DeMuth, Christopher M. Haqq, Eileen M. O'Reilly. T cell responses and clinical outcomes in pancreatic and colorectal cancer patients with minimal residual disease in AMPLIFY-201, a phase 1 trial of a first-in-class amphiphile lymph node targeted mutant KRAS vaccine [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr C092.

Predictive value of Global Leadership Initiative on Malnutrition criteria combined with handgrip strength for postoperative outcomes in overweight colorectal cancer patients.

The Global Leadership Initiative on Malnutrition (GLIM) criteria are increasingly used to assess the nutritional status of hospitalized patients and predict the prognosis of patients with malignant tumors; however, malnutrition is often overlooked in overweight individuals, such as colorectal cancer patients. This study aimed to investigate the predictive value of the GLIM criteria combined with handgrip strength (HGS) in overweight colorectal cancer patients. This retrospective study enrolled overweight patients who underwent radical resection for colorectal cancer at two centers between 2015 and 2021. Malnutrition was diagnosed based on the GLIM criteria. Skeletal muscle mass was assessed using the skeletal muscle index, and skeletal muscle function was assessed using the HGS test. The risk factors for complications and survival were also evaluated. A total of 850 patients were enrolled in the study. The incidence of malnutrition in the GLIM and HGS-GLIM groups was 12.4% and 6.4%, respectively. The incidence of total complications in both the malnutrition groups was significantly higher than that in the control group. Patients in the HGS-GLIM-malnutrition group had worse overall survival and disease-free survival. HGS-GLIM was independently associated with postoperative complications (P=0.046), overall survival (P=0.037), and disease-free survival (P=0.047). The GLIM criteria combined with the HGS test is an effective tool for diagnosing malnutrition. Particularly, these modalities are applicable in overweight colorectal cancer patients. Compared with the standard GLIM criteria, this tool has a better predictive value for postoperative complications and long-term survival.

Evaluation of mismatch-repair and microsatellite-instability status in a Chinese colorectal cancer Cohort

BackgroundImmunohistochemistry (IHC) and traditional polymerase chain reaction (PCR) are the methods of choice in clinical practice to identify the mismatch repair (MMR) and microsatellite instability (MSI) status in colorectal cancer (CRC). In some previous researches, the concordance rate between two methods was different and discordance existed in about 1 %–9.7 %. MethodsWe retrospectively reviewed 406 patients received surgical CRC resections and tests of both MMR IHC and MSI PCR from January 2019 to April 2022 in Shanghai Changzheng Hospital. The incidence of deficient mismatch repair (dMMR) or microsatellite instability-high (MSI-H) CRCs, the concordance rate between two methods, and the reasons for discordant results were evaluated with clinicopathological data, immunochemical staining, whole-exome sequencing, and MLH1 methylation analysis. ResultsAmong 406 patients, the incidence of MSI-H CRCs was 7.88 %. Nearly a quarter of the cases under reexamination of IHC was initial misinterpreted. Besides, the concordance rate between MMR IHC and MSI PCR was 99.26 % (401 of 404) and the Kappa value was 0.945 (p < 0.001). Finally, some somatic variants of MMR and POLE genes which may explain the discordance were identified. ConclusionThe incidence rate of MSI-H in Chinese patients with CRC might be relatively low owing to tumor location. Although MSI and IHC analyses are highly concordant, both MMR IHC and MSI PCR tests should be simultaneously performed and MMR IHC should be interpreted by experienced pathologists. In the future, further studies on discordant results should be carried out to improve the personalized management of CRC.

Acetone compression improves lymph node yield and metastasis detection in colorectal cancer.

Lymph node status is one of the most important prognostic factors in colorectal cancer, and accurate pathological nodal staging and detection of lymph node metastases is crucial for determination of post-operative management. Current guidelines, including the TNM staging system and European Society for Medical Oncology (ESMO) guidelines, recommend examination of at least 12 lymph nodes. However, identification of an adequate number of lymph nodes can be challenging, especially in the setting of neoadjuvant treatment, which may reduce nodal size. In this study, we investigated 384 colorectal cancer resections that were processed at our department of pathology between January 2012 and December 2022, in which the number of detected lymph nodes was less than 12 subsequent to conventional preparation of mesocolic fat tissue. By means of acetone compression, lymph node harvest increased significantly (p < 0.0001), and the intended number of ≥ 12 lymph nodes was achieved in 98% of resection specimens. The number of nodal positive cases increased significantly from n = 95 (24.7%) before versus n = 131 (34.1%) after acetone compression due to additionally identified lymph node metastases (p < 0.001). In 36 patients (9.4%) initially considered as nodal negative, acetone compression led to a staging adjustment to a nodal positive category and thereby drove a recommendation to offer post-operative therapy. In conclusion, acetone compression is a reliable and useful method implementable in routine surgical pathology for the retrieval of lymph nodes in colorectal cancer specimen, allowing for an adequate lymph node sampling and an increase in nodal staging reliability.

The diagnostic yield of colonoscopic surveillance following resection of early age onset colorectal cancer.

The primary benefit of post-colorectal cancer (CRC) colonoscopic surveillance is to detect and remove premalignant lesions to prevent metachronous CRC. Current guidelines for long-term colonoscopic surveillance post early age onset CRC (EOCRC) resection are based on limited evidence. The aims of this study were to assess the diagnostic yield of colonoscopic surveillance post-EOCRC resection and identify molecular and clinicopathological risk factors associated with advanced neoplasia. A retrospective cohort study of prospectively collected data was conducted at St Mark's hospital, London, United Kingdom, for patients diagnosed with EOCRC who underwent at least one episode of post-CRC colonoscopic surveillance between 1978 and 2022. We collected clinicopathological data including tumour molecular status and neoplasia detection rates. In total, 908 colonoscopic surveillance procedures were performed in 195 patients over 2581.3 person-years of follow-up. The diagnostic yields of metachronous CRC, advanced adenomas and non-advanced adenomas were 1.76%, 3.41% and 22.69% respectively. Sixteen patients (8.21%) developed metachronous CRC, and the majority (87.5%) were detected more than 3years post index EOCRC diagnosis. Detection of advanced neoplasia was significantly higher in EOCRC patients with Lynch syndrome (26.15%) compared with those in whom Lynch syndrome was excluded (13.13%) (OR, 2.343; 95% CI, 1.014-5.256; p=0.0349). During colonoscopic surveillance post-EOCRC resection, the long-term risk of developing metachronous advanced neoplasia remains high in the context of Lynch syndrome, but this trend is not as clearly evident when Lynch syndrome has been excluded.