Chemotherapy For Colon Cancer Research Articles

Effect of Resistance Training on Physical Function During Chemotherapy in Colon Cancer.

The decline of physical function during chemotherapy predicts poor quality of life and premature death. It is unknown if resistance training prevents physical function decline during chemotherapy in colon cancer survivors. This multicenter trial randomized 181 colon cancer survivors receiving postoperative chemotherapy to home-based resistance training or usual care control. Physical function outcomes included the short physical performance battery (SPPB), isometric handgrip strength, and the physical function subscale of the Medical Outcomes Short-Form 36-item questionnaire. Mixed models for repeated measures quantified estimated treatment differences (ETD). At baseline, subjects had a mean (SD) age of 55.2 years (12.8); 67 (37%) were ≥60 years, and 29 (16%) had a composite SPPB score ≤9. Compared with control, resistance training did not improve the composite SPPB score [ETD: -0.01 (95% CI: -0.32, 0.31); P = 0.98], or the SPPB scores for balance [ETD: 0.01 (95% CI: -0.10, 0.11); P = 0.93], gait speed [ETD: 0.08 (95% CI: -0.06, 0.22) P = 0.28], and sit-to-stand [ETD: -0.08 (95% CI: -0.29, 0.13); P = 0.46]. Compared with control, resistance training did not improve isometric handgrip strength [ETD: 1.50 kg (95% CI: -1.06, 4.05); P = 0.25] or self-reported physical function [ETD: -3.55 (95% CI: -10.03, 2.94); P = 0.28]. The baseline SPPB balance score [r=0.21 (95% CI: 0.07, 0.35)] and handgrip strength [r=0.23 (95% CI: 0.09, 0.36)] correlated with chemotherapy relative dose intensity. Among colon cancer survivors with relatively high physical functioning, randomization to home-based resistance training did not prevent physical function decline during chemotherapy. NCT03291951.

19P Adjuvant chemotherapy in colon cancer: 6 months better than 3?

19P Adjuvant chemotherapy in colon cancer: 6 months better than 3?

23P Renal impairment evaluation on postoperative (adjuvant) chemotherapy for colon cancer

23P Renal impairment evaluation on postoperative (adjuvant) chemotherapy for colon cancer

Improving outcomes in high-grade goblet cell adenocarcinomas: The interplay of complete cytoreduction, HIPEC and fibrosis.

e16379 Background: High-grade goblet cell adenocarcinomas (GCA), including signet-ring cell type (SRC) and poorly differentiated, behave more aggressively compared to typical GCA and are associated with poor prognosis. Due to GCA’s rarity, the treatment aligns with colon cancer guidelines, including surgery, chemotherapy and/or cytoreductive surgery (CRS) with Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for peritoneal carcinomatosis (PC). In our case series, we assessed the outcome of patients with high grade GCA tumors and PC, who underwent either CRS with HIPEC or tumor debulking. Methods: A prospectively maintained database of patients treated at the Division of Surgical Oncology for Peritoneal Carcinomatosis (PC) from 2007 to 2022 was reviewed retrospectively. Patient selection was based on the primary tumor’s original pathology report and scheduling to undergo CRS/HIPEC for PC. We calculated median overall survival from the time of diagnosed peritoneal carcinomatosis, with focus on the attainment of complete cytoreduction (CC) and HIPEC administration. Results: 385 records were screened and 21 cases of GCA were identified. Thirteen (13) patients had a diagnosis of high-grade GCA with PC. Complete cytoreduction (CC0/CC1) with HIPEC was achieved in 7/13 patients, and 6/13 patients underwent tumor debulking. The median overall survival after diagnosing peritoneal carcinomatosis was 53 months for the patients who underwent CC/HIPEC and 20 months for the patients who received debulking. Of note, in the debulking group, 5/6 patients had a poorly differentiated GCA and exhibited intraoperatively tumor characteristics of infiltration, thickening and fibrosis, confirmed by the pathology report, which rendered CC unsuccessful. In contrast, within the CC/HIPEC group, pathology reported localized fibrosis as a chemotherapy response in only 2/7 patients, which did not impede the achievement of CC. Preoperative 5-FU based chemotherapy was administered to 4/7 patients in the CC/HIPEC group and to 5/6 patients in the debulking group. Conclusions: Our results demonstrate that CC with HIPEC may improve overall survival in patients with high grade GCA with PC. Notably, poorly differentiated GCA and the presence of fibrotic tissue, stemming from the tumor and/or preoperative chemotherapy, influences CC success. Considering the potential impact of fibrosis on surgical outcomes, pathological assessment of fibrosis preoperatively and/or use of fibrosis-specific biomarkers could guide cytoreduction strategies and treatment choices in patients diagnosed with high-grade GCA.

The prognostic and predictive significance of perineural invasion in stage I to III colon cancer: a propensity score matching-based analysis

BackgroundColorectal cancer (CRC) presents with varying prognoses, and identifying factors for predicting metastasis and outcomes is crucial. Perineural invasion (PNI) is a debated prognostic factor for CRC, particularly in stage I-III patients, but its role in guiding adjuvant chemotherapy for node-positive colon cancer remains uncertain.MethodsWe conducted a single-center study using data from the Colorectal Section Tumor Registry Database at Chang Gung Memorial Hospital, Taiwan. This prospective study involved 3,327 CRC patients, 1,536 of whom were eligible after application of the exclusion criteria, to investigate the prognostic value of PNI in stage I-III patients and its predictive value for node-positive/negative cancer patients receiving adjuvant chemotherapy. Propensity score matching (PSM) was used to minimize selection bias, and follow-up was performed with standardized procedures.ResultsPNI-positive (PNI+) tumors were associated with higher preoperative CEA levels and more frequent adjuvant chemotherapy. After PSM, PNI + tumors were associated with marginally significantly lower 5-year disease-free survival (DFS) and significantly lower overall survival (OS) rates in stages III CRC. However, no significant differences were observed in stages I and II. Subgroup analysis showed that among PNI + tumors, only poorly differentiated tumors had higher odds of recurrence. PNI did not predict outcomes in node-negative colon cancer. Adjuvant chemotherapy benefited PNI + patients with node-positive but not those with node-negative disease.ConclusionsOur study indicates that PNI is an independent poor prognostic factor in stage III colon cancer but does not predict outcomes in node-negative disease. Given the potential adverse effects of adjuvant chemotherapy, our findings discourage its use in node-negative colon cancer when PNI is present.

Tumor penetrating Janus prodrug nanoassemblies for enhanced synergistic chemotherapy and photodynamic therapy of colon cancer

Intelligent nanodrug delivery systems that respond to tumor microenvironment have been extensively utilized in cancer therapy research. However, the passive diffusion of prodrug nanoparticles is hindered due to the absence of capillaries and dense extracellular matrix in the tumor microenvironment, resulting in low efficiency of anti-tumor drug delivery. In this study, we developed a metal matrix proteinase 2 (MMP2) and glutathione (GSH) responsive Janus prodrug nanoassemblies targeted towards tumors. The Janus prodrug nanoassemblies consist of targeted micelles and prodrug nanoaggregates linked by click chemistry. The size of the nanoassemblies can be reduced within the tumor microenvironment of high concentrations of MMP2. Active targeting and size shrinkage synergistically enhance cell uptake efficiency and tumor penetration capacity of nanoassemblies. The release of camptothecin (CPT) occurs in a GSH-dependent manner, while under irradiation with 660-nm red light, the photosensitizer introduced in the prodrug generates reactive oxygen species (ROS) to induce tumor cell death. Fluorescence imaging results demonstrate enhanced tumor targeting capabilities of Janus prodrug assemblies. As a theranostic agent for tumors, Janus prodrug assemblies achieve desirable synergistic chemotherapy and photodynamic therapy for colon cancer treatment. This work would provide a novel strategy for cancer diagnosis and treatment.

Race/Ethnicity and Social Determinants of Health and Their Impact on Receiving Appropriate Chemotherapy for Colon Cancer.

Despite the heightened understanding and improved treatment for colorectal cancer in the United States, social determinants of health (SDH) play a significant role in the colorectal cancer outcomes. We sought to investigate the relationship between SDH and appropriate utilization of adjuvant chemotherapy in stage III colon cancer. For this retrospective study, we utilized data from the National Cancer Data Base (NCDB). Descriptive statistics are reported, including means and 95% confidence intervals for continuous variables and frequency and proportions for categorical variables. Univariate hypothesis testing to identify categorical level factors associated with treatment used Wilcoxon rank sum or Kruskal-Wallis tests, with multivariate analyses performed using regression analysis. Significant differences were as follows: Metro-non-Hispanic White patients received treatment less frequently (69.7%) when compared to Metro-non-Hispanic Black patients (73.4%) (P < .001). Increasing age was a negative predictor of likelihood to receive with those over 65years old having an 83% decrease in likelihood to receive chemotherapy when compared to those under 65 (P < .001). Medicaid patients were 47% less likely and Medicare patients were 40% less likely to receive chemotherapy when compared to those with private insurance (P < .001). Rural patients were statistically more likely to receive chemotherapy (OR 1.42, 1.32-2.52, P < .001) as were urban patients, (OR 1.26, 1.20-1.31, P < .001) when compared to patients residing in metro areas. Age, living in a Metro area, and government insurance status at diagnosis are negatively correlated with the likelihood of receiving chemotherapy. Race was not associated with differences in receiving chemotherapy.

A Clinical Study of Intraoperative Perfusion Chemotherapy With Raltitrexed in Colon Cancer: A Prospective Cohort Study.

Colorectal cancer (CRC) ranks as the second leading cause of cancer-related mortality among women and the third leading cause of cancer-associated mortality among men. Treatment of colon cancer is very crucial for a patient's survival. In this study, we assessed the reliability, efficacy, and safety of raltitrexed in intraoperative intraperitoneal chemotherapy for colon cancer. A total of 57 patients with clinical stages II and III of colon cancer were included in the study. R0 resection surgery + hyperthermic intraperitoneal chemotherapy (HIPEC) procedure was done with raltitrexed. It was given in a dose of 3 mg/m2 in a 0.9% NS injection in a volume of 500 milliliters. Postoperative complications were observed. The most common postoperative complication was nausea/vomiting, which was seen in 21 out of 57 patients (37%). The second most common complication was fever (18/57). None of the patients died or developed renal toxicity, hepatic toxicity, and intestinal obstruction. Raltitrexed is a reliable, efficient, and safe drug and can be used in intraoperative intraperitoneal chemotherapy of colon cancer.

Abstract 507: HLS-22001 induces G2/M cell cycle arrest and apoptotic cell death via tubulin depolymerization in colon cancer

Abstract Colorectal cancer (CRC) is one of the main malignant tumors and among the leading cause of death in cancer patients worldwide considering that recurrence and chemotherapeutic drug resistance are highly common in the advanced stage of CRC. Mutations in KRAS and BRAF occur frequently in colorectal cancers, and abnormal cell cycles caused by these mutations affect tumor progression and metastasis. Accordingly, inhibition of cell cycle has been a potential target for colorectal cancers and therefore, we have developed a new lead compound, HLS-22001. Our studies confirmed that HLS-22001 inhibited the proliferation of several cancer cells and significantly induced G2/M arrest and apoptosis of colon cancer cells and chemotherapy resistant colon cancer cells. The docking model studies showed that HLS-22001 was expected to bind to the colchicine binding site of beta-tubulin, and in fact, as a tubulin inhibitor, it had the effect of inhibiting tubulin dimerization and polymerization in the microtubule dynamics. Consistently, in xenograft mouse model, oral administration of HLS-22001 significantly suppressed tumor weight and volume without acute toxicity in mice. Collectively, these results suggest further development of HLS-22001 as a novel and promising oral drug for colorectal cancer. Citation Format: Chi-hyun Ahn, Gyu-beom Jang, Chunhwa Kim, Junho Lee, Taewon Kim, Youngeun Yang, Eunji Cho, Minchae Kim, Yun-tai Kim, Yong-Hae Han, Heebum Kang. HLS-22001 induces G2/M cell cycle arrest and apoptotic cell death via tubulin depolymerization in colon cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 507.

Colon cancer: feeling the imbalance?

While neoadjuvant chemotherapy has become the standard of care for rectal cancers in most centres, there is much interest in neoadjuvant chemotherapy in colon cancer after the recent publication of the FOxTROT trial. The management of colon cancers seems to be heading down the same path as rectal cancer, where the radicality of surgery is replaced by chemotherapy intensification. The role of demanding procedures such as complete mesocolic excision with central venous ligation in this new paradigm of upfront chemotherapy remains uncertain and uninvestigated.

Imaging of carboxylesterase 2 expression changes in colitis and colon cancer chemotherapy via a fluorescent probe

Colitis is one of the important etiologies of colon cancer, but the diagnosis of early colitis and colon cancer is still a difficult problem, so it is important to use reasonable methods to achieve the diagnosis of early colitis and colon cancer. Carboxylesterase 2 (CES2) is momentous in the development of colon disease and can be used as an indicator to distinguish colitis from colon cancer. CES2 is expressed differently in colitis and colon cancer, so it has the potential to distinguish colitis from colon cancer by detecting the difference in CES2 expression. We designed a fluorescent probe Bcy-CES2 for imaging CES2 in cells and in vivo and evaluating the differences in CES2 levels in colon disease. Probe Bcy-CES2 shows good potential for in situ real-time monitoring of endogenous CES2. In addition, we found that the combination of CES2 inhibitor BNPP and cisplatin can reduce tumor chemotherapy resistance, and CES2 levels may become a new index for early diagnosis and prognosis of colon cancer.

Neoadjuvant Chemotherapy in Patients With T4b or Obstructive Colon Cancer: A Single Center Retrospective Cohort Study.

The efficacy of neoadjuvant chemotherapy (NAC) for colon cancer remains unestablished. This study aimed to investigate the outcomes of NAC in patients with locally advanced T4b or obstructive T4a colon cancers (LACC). Data of patients with LACC who underwent colon surgery between 2010 and 2022 after NAC at our institution were retrospectively reviewed. Patient characteristics, surgical outcomes, tumor features, and prognosis were analyzed. Among 800 patients with LACC who underwent radical resection, 11 received NAC because of cT4b or cT4a with mechanical obstruction. NAC, administered as a doublet regimen, had a median duration of three months, without grade ≥3 adverse events. R0 resection was achieved in all patients and downstaging was observed in eight patients. One patient developed a postoperative abdominal abscess, and adjuvant chemotherapy was administered to eight patients. Four patients experienced recurrence: liver metastasis in two, and local recurrence in two. Among these, three patients underwent resection of recurrent tumors. Median follow-up was 30 months. NAC is feasible for T4b or obstructive T4a colon cancer and may be a treatment option for LACC. Further large-scale studies are required to confirm the efficacy of NAC in these patients.

Oxygen-supplying ROS-responsive prodrug for synergistic chemotherapy and photodynamic therapy of colon cancer.

Introduction: The synergistic treatment of chemotherapy and photodynamic therapy (PDT) has remarkable potential in cancer therapy. However, challenges remain, such as unstable chemotherapeutic drug release, suboptimal targeting, and reduced efficacy of PDT under hypoxic conditions commonly found in solid tumors. Methods: To address these issues, we use camptothecin (CPT) and pheophorbide a (Pa) incorporated through the functional thioketal, which serves as the reactive oxygen species (ROS)-responsive trigger, to construct a ROS-responsive prodrug (CPT-TK-Pa). Subsequently, we co-loaded it with a platinum nanozyme (PtNP) in distearylphosphatidylethanolamine-polyethylene glycol (DSPE-PEG) to obtain the ROS-responsive prodrug nanoparticle (CPT-TK-Pa/Pt NP). Results and Discussion: Specifically, the incorporated PtNP within CPT-TK-Pa/Pt NP positively catalyzes the conversion of hydrogen peroxide (H2O2) to oxygen, thereby ameliorating the hypoxic state of the tumor. This enhanced oxygen generation could replenish the oxygen that is consumed by Pa during 660nm exposure, enabling controlled CPT release and amplifying the photodynamic response. In vitro investigations reveal the potency of CPT-TK-Pa/Pt NPs in inhibiting colon tumor cells. Given its ROS-responsive release mechanism and enhanced PDT efficacy, CPT-TK-Pa/Pt NP has the potential to be a promising candidate for cancer therapy.

Advances in Adherence Reporting of Resistance Training in a Clinical Trial during Adjuvant Chemotherapy for Colon Cancer.

Detailed reporting of individually tailored exercise prescriptions (ExR x ) used in clinical trials is essential to describe feasibility, tolerability, and efficacy of the intervention and to inform translation to clinical care. This article outlines the methodology used to develop a resistance training (RT) ExR x for people with colon cancer receiving chemotherapy and reports adherence to the randomized controlled trial testing the impact of RT on relative dose intensity of chemotherapy and patient-reported toxicities. Participants randomized to the exercise arm ( n = 90) were included. To promote muscle hypertrophy, the ExR x was twice-weekly, moderate to heavy loads (65%-85% one-repetition maximum), high sets (3-5), and intermediate repetitions (6-10) of five large multijoint movements with adjustable dumbbells. Attendance (achieved frequency) and adherence (achieved volume) were calculated. Group-based trajectory modeling was used to identify clusters of individuals with similar adherence patterns and compared baseline characteristics across adherence groups. The median attendance was 69.1%. Adherence was 60.6% but higher for those receiving 3 versus 6 months of chemotherapy (80.4 vs 47.4%; P < 0.05 ). Participants engaged in a median of 1.4 d of RT each week, lifting 62% of the one-repetition maximum load, for 3.0 sets and 7.5 repetitions per set. Three distinct adherence groups were identified: 13% "nonstarter," 37% "tapered off," and 50% "consistent exercisers." Females were more likely to be in the nonstarter and tapered-off groups. This article outlines suggested methods for reporting ExR x of RT in oncology clinical trials and provides insight into the tolerance of ExR x of RT during chemotherapy treatment for colon cancer. These findings aim to foster constructive dialogue and offer a premise for designing future research to elucidate the benefits of exercise during chemotherapy.

SiRNF8 Delivered by DNA Framework Nucleic Acid Effectively Sensitizes Chemotherapy in Colon Cancer.

The evident side effects and decreased drug sensitivity significantly restrict the use of chemotherapy. However, nanoparticles based on biomaterials are anticipated to address this challenge. Through bioinformatics analysis and colon cancer samples, we initially investigated the expression level of RNF8 in colon cancer. Next, we constructed nanocarrier for delivering siRNF8 based on DNA tetrahedron (si-Tet), and Doxorubicin (DOX) was further intercalated into the DNA structure (si-DOX-Tet) for combination therapy. Further, the effects and mechanism of RNF8 inhibition on the sensitivity of colon cancer cells to DOX chemotherapy have also been studied. RNF8 expression was increased in colon cancer. Agarose gel electrophoresis, transmission electron microscopy, and size distribution and potential analysis confirmed the successful preparation of the two nanoparticles, with particle sizes of 10.29 and 37.29 nm, respectively. Fluorescence imaging reveals that the carriers can be internalized into colon cancer cells and escape from lysosomes after 12 hours of treatment, effectively delivering siRNF8 and DOX. Importantly, Western blot analysis verified treatment with 50nM si-Tet silenced RNF8 expression by approximately 50% in colon cancer cells, and combined treatment significantly inhibited cell proliferation. Furthermore, the CCK-8 assay demonstrated that si-Tet treatment enhanced the sensitivity of colon cancer cells to the three chemotherapeutic drugs. Significant more DNA damage was detected after treatment with both si-Tet or si-DOX-Tet. Further flow cytometry analysis revealed that si-DOX-Tet treatment led to significantly more apoptosis, approximately 1.6-fold higher than treatment with DOX alone. Mechanistically, inhibiting RNF8 led to decreased ABCG2 expression and DOX efflux, but increased DNA damage, thereby enhancing the chemotherapeutic effect of DOX. We have successfully constructed si-DOX-Tet. By inhibiting the expression of RNF8, it enhances the chemotherapy sensitivity of DOX. Therefore, this tetrahedral FNA nanocarrier offers a new approach for the combined treatment of colon cancer.

Risk of Bowel Obstruction in Patients Undergoing Neoadjuvant Chemotherapy for High-risk Colon Cancer: A Nested Case-control Matched Analysis of an International, Multi-centre, Randomised Controlled Trial (FOxTROT).

This study aimed to identify risk-criteria available before the point of treatment initiation that can be used to stratify risk of obstruction in patients undergoing neoadjuvant chemotherapy (NAC) for high-risk colon cancer. Global implementation of neoadjuvant chemotherapy (NAC) for colon cancer, informed by the FOxTROT trial, may increase risk of bowel obstruction. A case-control study, nested within an international randomised controlled trial (FOxTROT. ClinicalTrials.gov: NCT00647530). Patients with high-risk operable colon cancer (radiologically-staged T3-4 N0-2 M0) that were randomised to NAC and developed large bowel obstruction were identified. Firstly, clinical outcomes were compared between patients receiving NAC in FOxTROT that did and did not develop obstruction. Secondly, obstructed patients (cases) were age- and sex-matched with patients that did not develop obstruction (controls) in a 1:3 ratio using random sampling. Bayesian conditional mixed-effects logistic regression modelling was used to explore clinical, radiological, and pathological features associated with obstruction. Absolute risk of obstruction based on the presence or absence of risk criteria was estimated for all patients receiving NAC. Of 1053 patients randomised in FOxTROT, 699 received NAC, of whom 30 (4.3%) developed obstruction. Patients underwent care in European hospitals including 88 UK, 7 Danish and 3 Swedish centres. There was more open surgery (65.4% vs. 38.0%, P =0.01) and a higher pR1 rate in obstructed patients (12.0% vs. 3.8%, P =0.004), but otherwise comparable postoperative outcomes. In the case-control matched Bayesian model, two independent risk criteria were identified: (1) obstructing disease on endoscopy and/or being unable to pass through the tumour (adjusted odds ratio: 9.09, 95% credible interval: 2.34-39.66) and stricturing disease on radiology or endoscopy (OR: 7.18, 95% C.I.: 1.84-32.34). Three risk groups were defined according to the presence or absence of these criteria: 63.4% (443/698) of patients were at very low risk (<1%), 30.7% (214/698) at low risk (<10%), and 5.9% (41/698) at high risk (>10%). Safe selection for NAC for colon cancer can be informed by using two features that are available before treatment initiation and identify a small number of patients with high risk of preoperative obstruction.

Racial Disparities in Receipt of Guideline-Concordant Care for Early-Onset Colorectal Cancer in the United States.

Young individuals racialized as Black are more likely to die after a colorectal cancer (CRC) diagnosis than individuals racialized as White in the United States. This study examined racial disparities in receipt of timely and guideline-concordant care among individuals racialized as Black and White with early-onset CRC. Individuals age 18-49 years racialized as non-Hispanic Black and White (self-identified) and newly diagnosed with CRC during 2004-2019 were selected from the National Cancer Database. Patients who received recommended care (staging, surgery, lymph node evaluation, chemotherapy, and radiotherapy) were considered to have received guideline-concordant care. Odds ratios (ORs) were adjusted for age and sex. The decomposition method was used to estimate the relative contribution of demographic characteristics (age and sex), comorbidities, health insurance, and facility type to the racial disparity in receipt of guideline-concordant care. The product-limit method was used to evaluate differences in time to treatment between patients racialized as Black and White. Of the 84,882 patients with colon cancer and 62,573 patients with rectal cancer, 20.8% and 14.5% were racialized as Black, respectively. Individuals racialized as Black were more likely to not receive guideline-concordant care for colon (adjusted OR [aOR], 1.18 [95% CI, 1.14 to 1.22]) and rectal (aOR, 1.27 [95% CI, 1.21 to 1.33]) cancers. Health insurance explained 28.2% and 21.6% of the disparity among patients with colon and rectal cancer, respectively. Individuals racialized as Black had increased time to adjuvant chemotherapy for colon cancer (hazard ratio [HR], 1.28 [95% CI, 1.24 to 1.32]) and neoadjuvant chemoradiation for rectal cancer (HR, 1.42 [95% CI, 1.37 to 1.47]) compared with individuals racialized as White. Patients with early-onset CRC racialized as Black receive worse and less timely care than individuals racialized as White. Health insurance, a modifiable factor, was the largest contributor to racial disparities in receipt of guideline-concordant care in this study.

Cumulative incidence of first recurrence after curative treatment of stage I–III colorectal cancer. Competing risk analyses of temporal and anatomic patterns

Background Updated knowledge about the rates of recurrence and time to recurrence following curative treatment of colorectal cancer is essential to secure better patient information on prognosis, to serve as a premise in the discussion on adjuvant chemotherapy, and help to properly scale the intensity and length of follow-up. Methods This is a population-based study investigating aspects on first recurrence after radical treatment of clinical stages I-III of colorectal cancer in Central-Norway during 2001–2015. To reveal any time-trends, data were stratified by the time periods 2001–2005, 2006–2010 and 2011–2015. The cumulative incidence of first recurrence was calculated, treating death of unrelated causes as a competing event. Multivariable Cox analyses were done to calculate cause specific hazard ratios (HR) for risk of recurrence. Results At a minimum follow-up of six years, a first recurrence was detected in 1,113/5,556 patients at risk (20.0%). The recurrence rate was reduced from 23.6% in the first time period, through 20.0% in the second, and to 17.2% in the last, p < 0.001. The reduction applied to all tumor locations, to pathological disease stages II and III, to both gender, across different tumor differentiations, and to both elective and emergency surgery. In multivariable analyses time period, gender, disease stage, and tumor differentiation were significant determinants for risk of recurrence. Conclusions The rate of first recurrence after curative surgery for colorectal cancer was substantially reduced from 2001 to 2015. The reason for the reduction could not be attributed to a single factor only. A combined effect of several incremental improvements, such as an increased use of preoperative radiation for rectal cancers, improved adjuvant chemotherapy for colon cancer, and a reduced proportion of emergency surgery, is suggested.

Effcacy and toxicity of regorafenib compared to reintrodaction of chemotherapy in metastatic colon cancer: retrospective multicenter study

The objective of the study is to compare the effectiveness of various systemic therapies in the 3rd and subsequent lines of therapy of metastatic colon cancer. Material and Methods. Retrospective multicenter study collected data from 2 clinics of the Russian Federation. We considered overall survival (OS) as the main criterion of effectiveness. Progression-free survival (PFS) was the additional criterion. We performed a single- and multifactorial analysis of the effect of various parameters on PFS. To evaluate the effectiveness of regorafenib and the reintroduction of previously effective drugs, we should prove the equivalence of reintroduction of the 3rd line chemotherapy (CT) and targeted therapy to regorafenib on the 6-month overall survival, provided that the equivalence boundaries would be between 0.8 and 1.25. To reach the 0.05 probability of type I error and the 80 % study power, 178 patients (89 in each group) should be included in the study. Results. The database identifed 215 patients with morphologically confrmed metastatic colon cancer who received two or more lines of antitumor drug therapy from 2010 to 2021. We selected 132 patients with the history of regorafenib therapy and 83 patients with the reintroduction of a previously used chemotherapy regimen as 3rd line treatment. The median OS in the reintroduction and regorafenib groups did not differ (HR, 1.01; 95 % CI, 0.7–1.45; p=0.920); 6-month OS were 74 and 70 %, respectively. Progression-free survival was signifcantly higher in the reintroduction group (HR, 1.94; 95 % CI, 1.3–2.7; p&lt;0.001). Multivariate analysis showed that the reintroduction of previous treatment regimens kept its independent positive effect on PFS (HR, 1.9; 95 % CI, 1.3–2.8; p&lt;0.001). In our study, toxicity on the 3rd line of CT developed in 117 (54.4 %) of 215 patients and signifcantly more frequent in the regorafenib group: 67.4 % (89/132) vs 33.7 % (28/83) in the group with repeated administration of previously effective regimens (p&lt;0.001). Conclusion. Regorafenib and reintroduction of the previous treatment in the 3rd line did not differ in overall survival. Progression-free survival was signifcantly higher in the reintroduction group as the 3rd line of treatment, with signifcantly lower toxicity.

A national evaluation of adjuvant chemotherapy in pT4N0M0 colon cancer from the National Cancer Database.

T stage is a prognostic biomarker for overall survival in colon cancer and pathologic T4 disease is a high-risk characteristic. Adjuvant chemotherapy is recommended to improve overall survival in pT4N0M0, but compliance with guidelines is unknown. We aimed to evaluate adjuvant chemotherapy use and impact on overall survival in pT4N0M0 colon cancer. The National Cancer Database was reviewed for pT4N0M0 colon adenocarcinomas undergoing curative surgical resection (2010-2017). Cases were stratified into no adjuvant chemotherapy and adjuvant chemotherapy cohorts. Moderated multiple regression assessed factors associated with no AC. Kaplan-Meier and Cox regression assessed overall survival in propensity-score matched cohorts. The main outcome measures were adjuvant chemotherapy use, factors associated with adjuvant chemotherapy, and impact on overall survival. Of 11 847 cases, 62.4% (n = 7391) received no adjuvant chemotherapy. With private insurance, comorbidities or income do not affect adjuvant chemotherapy use. Medicare cases with a Charlson-Deyo comorbidity index of 0 (odds ratio [OR] = 0.861, 95% confidence interval [CI] = 0.760 to 0.975; P = .019) and Medicare payors with high income (OR = 0.813, 95% CI = 0.690 to 0.959; P = .014) were associated with adjuvant chemotherapy. Medicaid Charlson-Deyo comorbidity index 0 (OR = 1.374, 95% CI = 1.125 to 1.679; P = .002) and uninsured Charlson-Deyo comorbidity index 0 (OR = 1.351, 95% CI = 1.120 to 1.629; P = .002) were associated with no adjuvant chemotherapy. Adjuvant chemotherapy was associated with improved 5-year overall survival (71.7% vs 56.4%; P < .001; adjusted hazard ratio = 0.543, 95% CI = 0.499 to 0.590; P < .001). Although adjuvant chemotherapy is associated with improved overall survival, compliance is low. There is a complex relationship between payor, income, comorbidity, and adjuvant chemotherapy receipt. Medicare patients with no comorbidities or higher income have better adjuvant chemotherapy use. With private insurance, adjuvant chemotherapy compliance is not affected by comorbidities or income, whereas Medicaid and uninsured patients with no comorbidities have poor compliance. Future work could target these disparities for equitable care.