Prevalence and predictive factors of colorectal sessile serrated lesions in younger individuals.

BACKGROUND: Sessile serrated lesions (SSLs) are obscured lesions predominantly in the right-sided colon and associated with interval colorectal cancer; however, their prevalence and risk factors among younger individuals remain unclear. METHODS: This retrospective study enrolled individuals who underwent index colonoscopy. The primary outcome was the SSL prevalence in the younger (<50 years) and older (≥50 years) age groups, while the secondary outcomes included clinically significant serrated polyps (CSSPs). Multivariable logistic regression was employed to identify predictors. RESULTS: Of the 9854 eligible individuals, 4712 (47.8%) were categorized into the younger age group. Individuals in the younger age group exhibited lower prevalences of adenomas (22.6% vs. 46.2%; P<0.001) and right-sided adenomas (11.2% vs. 27.2%; P<0.001) compared with their older counterparts. However, both groups exhibited a similar prevalence of SSLs (7.2% vs. 6.5%; P=0.16) and CSSPs (10.3% vs. 10.3%;P=0.96). Multivariable analysis revealed that age 40-49 years (odds ratio [OR] 1.81, 95%CI 1.01-3.23), longer withdrawal time (OR 1.17, 95%CI 1.14-1.20, per minute increment), and endoscopist performance (OR 3.35, 95%CI 2.44-4.58) were independent predictors of SSL detection in the younger age group. No significant correlation was observed between adenoma and SSL detection rates among endoscopists. CONCLUSION: SSLs are not uncommon among younger individuals. Moreover, diligent effort and expertise are of paramount importance in SSL detection. Future studies should explore the clinical significance of SSLs in individuals of younger age.

Efficacy of transarterial chemoembolization with drug-eluting beads combined with systemic chemotherapy and targeted therapy in colorectal cancer liver metastasis.

BACKGROUND: Systemic therapy is the standard treatment for unresectable colorectal cancer with liver metastasis (CRCLM). Transarterial chemoembolization with drug-eluting beads (DEB-TACE) is considered an effective treatment option for CRCLM. Few studies have investigated the combination of DEB-TACE, chemotherapy, and targeted therapy for CRCLM. In the present study, we evaluated the disease control rate (DCR), adverse events, and survival among patients with CRCLM who underwent the combination of DEB-TACE and chemotherapy/targeted therapy. MATERIALS: We retrospectively reviewed 35 patients with CRCLM who were treated between January 2015 and January 2021. Standard systemic chemotherapy, targeted therapy, and 66 DEB-TACE procedures were administered. Data were collected on each DEB-TACE procedure, including chemotherapy agents, tumor burden of liver metastasis, number of DEB-TACE courses, and adverse events. Patients who received DEB-TACE after failure of first-line systemic therapy were categorized into the first-line failure group. Patients who received DEB-TACE after the failure of second-line, third-line, or fourth-line therapy were categorized into the other group. Subgroup analysis was performed to compare overall survival (OS) and progression-free survival (PFS) between the two groups. RESULTS: In total, 35 patients with CRCLM (34 patients with adenocarcinoma and 1 patient with neuroendocrine carcinoma) were enrolled. In total, 13 patients (37.1%) had extrahepatic metastases at initial diagnosis. In this study, 66 DEB-TACE procedures were performed. The DCR was 54.3%. The median OS period was 47.4 months, and the estimated 3-year OS rate was 59.5%. The median PFS period was 6.3 months, and the estimated 1-year PFS rate was 20.6%. The PFS period was longer in the first-line failure group than in the other group (7.2 vs. 6.3 months). No significant difference was observed in OS between the two groups. Four episodes (6.1%) of grade 3 intra-abdominal infection were observed. CONCLUSION: The combination of chemotherapy, targeted therapy, and DEB-TACE can lead to a favorable DCR and survival outcomes in patients with CRCLM. Early intervention with DEB-TACE (i.e., after the failure of first-line therapy) has the potential to extend the PFS period in patients with CRCLM. Severe adverse events were rare and manageable. Further prospective, randomized controlled studies are warranted to obtain more conclusive findings.

Real-World Outcomes of First-Line FOLFIRI Plus Bevacizumab with Irinotecan Dose Escalation versus FOLFOXIRI Plus Bevacizumab in BRAFV600E-Mutant Metastatic Colorectal Cancer: The Preliminary Data from a Single-Center Observational Study.

Background and Objectives: Approximately 5-10% of all patients with metastatic colorectal cancer (mCRC) harbor a BRAFV600E mutation. These patients exhibit distinct metastatic patterns, poor prognosis, and heterogenous survival outcomes. The findings from the TRIBE study indicated that the administration of FOLFOXIRI plus bevacizumab as first-line treatment extended the median duration of overall survival (OS). In this study, we explored the effects of UGT1A1 polymorphism on the outcomes of irinotecan dose escalation versus FOLFOXIRI plus bevacizumab in patients with BRAFV600E-mutant mCRC. Materials and Methods: We retrospectively reviewed the medical records of 25 patients who had received a diagnosis of BRAFV600E-mutant mCRC between October 2015 and August 2022. All patients underwent UGT1A1 genotyping before receiving bevacizumab plus FOLFIRI. The primary end point was progression-free survival (PFS), and secondary endpoints were OS and adverse events (AEs). The two treatment arms were compared in terms of 6-month PFS and 12-month OS. Results: Over a median follow-up duration of 15.0 (interquartile range, 10.0-30.5) months, no significant differences were noted between the treatment arms in severe AEs (SAEs), 6-month PFS, or 12-month OS (all p < 0.05). Regarding AEs, the FOLFIRI plus bevacizumab regimen was associated with a lower incidence of anorexia than was the FOLFOXIRI plus bevacizumab regimen (p = 0.042). Conclusions: Our findings indicate that FOLFIRI plus bevacizumab with irinotecan dose escalation is an effective first-line treatment regimen for patients with BRAFV600E-mutant mCRC. This regimen leads to acceptable clinical outcomes with manageable AEs. However, the effects on survival and safety outcomes could only be speculated, and further studies are needed because of the sample size, the follow-up for the OS evaluation, and the non-uniformity in all the variables considered in the two groups.

Clinical and cost-effectiveness analysis of mFOLOFX6 with or without a targeted drug among patients with metastatic colorectal cancer: inverse probability of treatment weighting.

This study investigated the cost-effectiveness and quality of life (QoL) within 1 year of receiving mFOLOFX6 with or without a targeted drug (bevacizumab or ramucirumab) as second-line treatment among patients with metastatic colorectal cancer (mCRC) following the failure of FOLFIRI + bevacizumab as first-line treatment. This prospective cohort study included patients who received a diagnosis of mCRC between March 2015 and May 2020. QoL was evaluated before treatment and at 6 months and 1 year posttreatment. All related variables were controlled using the inverse probability of treatment weighting method. Generalized estimating equations with the difference-in-difference method was used to explore changes in QoL. The incremental cost-utility ratio (ICUR) of the two groups was simulated using the annual-cycle Markov decision tree model. Finally, 39 and 76 patients were included in the targeted and nontargeted agent groups, respectively. At 6 months after treatment, QoL of the two groups improved significantly, but the targeted agent group had significantly better QoL than did the nontargeted agent group at 1 year posttreatment (P < 0.05). When the time frame was set to 20 years, the ICUR of the targeted agent group compared with the nontargeted agent group was US$32,052 per quality-adjusted life years. Addition of a targeted drug to the second-line mFOLOFX6 regimen not only improved the patients' QoL but was also more cost effective when the willingness-to-pay threshold was set at US$33,004 (the per capita gross domestic product of Taiwan). These patients should be reimbursed for these targeted agents by the National Health Insurance scheme in Taiwan.

The Auxiliary Effects of Low-Molecular-Weight Fucoidan in Locally Advanced Rectal Cancer Patients Receiving Neoadjuvant Concurrent Chemoradiotherapy Before Surgery: A Double-Blind, Randomized, Placebo-Controlled Study.

Patients with cancer use low-molecular-weight fucoidan (LMF) as a supplement to therapy. However, most studies of LMF are in vitro or conducted using animals. Concurrent chemoradiotherapy (CCRT) is the gold standard for locally advanced rectal cancer (LARC). This study investigated the quality of life (QoL) and clinical outcomes of patients with LARC taking LMF as a supplement to neoadjuvant CCRT. This was a double-blind, randomized, placebo-controlled study. The sample comprised 87 patients, of whom 44 were included in a fucoidan group and 43 were included in a placebo group. We compared their QoL scores and clinical outcomes before treatment, and at 1 month, 2 months, and 3 months posttreatment. Pretreatment and posttreatment gut microbiota differences were also compared. Although enhanced physical well-being (PWB) at 2 months and 3 months posttreatment in the fucoidan group were observed (both P < .0125), the improvements of the Functional Assessment of Cancer Therapy for Patients with Colorectal Cancer (FACT-C) were nonsignificant (all P > .0125). Skin rash and itching and fatigue were less common in the fucoidan group (both P < .05). Posttreatment, the genus Parabacteroides was significantly more common in the gut microbiota of the fucoidan group. LMF administration improved the QoL, skin rash and itching, fatigue, and gut microbiota composition of the patients with LARC receiving CCRT.Clinical Trial Registration: NCT04342949.

The emergence of RAS mutations in patients with RAS wild-type mCRC receiving cetuximab as first-line treatment: a noninterventional, uncontrolled multicenter study.

ABSRTACT: BACKGROUND: Patients treated with anti-epidermal growth factor receptor (anti-EGFR) will ultimately develop acquired resistance promoted by clonal selection, mainly the emergence of mutations in the MAPK pathway (mostly RAS mutations). Baseline assessment of RAS mutations in the blood of patients correlates well with RAS tumour tissue testing and is currently an alternative option in routine clinical practice to guide first-line therapy. The aim of this study was the prevalence of acquired genomic alterations detected in the auxiliary tool of ctDNA testing and investigated the role of RAS ctDNA status for detecting tumour response and predicting benefit to anti-EGFR therapy. METHODS: Only patients with concordant wild-type formalin-fixed, paraffin-embedded (FFPE) tumour tissue and baseline ctDNA RAS wild-type were included. RAS mutations in plasma were evaluated using MassARRAY platform. Blood samples were collected at baseline, every 3 months during first-line treatment, and at disease progression. The primary endpoint was the detection rate of RAS mutations during cetuximab treatment. The correlation between response and survival outcomes and the emergence of circulating RAS mutations was also analysed. RESULTS: The detection rate of RAS mutations during treatment was 9.3% (10/108). RAS mutations detection occurred a median of 3 months prior to radiologic documentation. The subgroup of patients with RAS mutations exhibited significantly inferior progression-free survival and overall survival (P = 0.002 and 0.027, respectively) but the baseline characteristics, response rates, disease control rates, and metastatectomy were not significant (all P > 0.05). CONCLUSIONS: We demonstrated that RAS ctDNA status might be a valuable biomarker for detecting early tumour response and predicting benefit to anti-EGFR therapy. CLINICAL TRIAL REGISTRATION: NCT03401957 (January 17, 2018).

Efficacy and Safety of a Parenteral Nutrition Program for Patients with RAS Wild-Type Metastatic Colorectal Cancer Administered First-Line Cetuximab Plus Chemotherapy: A Propensity Score Matching Study.

Malnutrition is a common problem in patients with metastatic colorectal cancer (mCRC) receiving targeted therapy plus chemotherapy, resulting in severe toxicity and decreased survival rates. This retrospective study employing propensity score matching (PSM) examined the efficacy and safety of a supplemental home parenteral nutrition (HPN) program for patients with RAS wild-type mCRC receiving cetuximab plus chemotherapy. This retrospective nationwide registry study included data from 14 medical centers/hospitals across Taiwan, and the data period ranged from November 2016 to December 2020. Patients with RAS wild-type mCRC receiving cetuximab plus chemotherapy as their first-line therapy were included and divided into HPN and non-HPN program groups. HPN was initiated based on patient-specific factors, such as baseline nutritional status, treatment-related toxicities, and comorbidities. Clinical outcomes were evaluated using response to therapy, duration of response (DoR), progression-free survival (PFS), and overall survival (OS). This study recruited 758 patients, of whom 110 and 648 were included in the HPN and non-HPN program groups, respectively. After 1:3 PSM, the data of 109 and 327 patients from the HPN and non-HPN program groups were analyzed, respectively. The HPN program group had a higher metastasectomy rate (33.9% vs. 20.2%, p = 0.005), and longer duration of treatment and DoR than the non-HPN program group (13.6 vs. 10.3 and 13.6 vs. 9.9 months, p = 0.001 and < 0.001, respectively). The HPN program group tended to have a longer median PFS (18.2 vs. 13.9 months, p = 0.102). Moreover, we noted a significant improvement in the median OS in the same group (53.4 vs. 34.6 months, p = 0.002). Supplemental HPN programs may be recommended for select patients with mCRC receiving targeted therapy plus chemotherapy to improve oncological outcomes.

Aptamer/doxorubicin-conjugated nanoparticles target membranous CEMIP2 in colorectal cancer.

The objectives were to identify the functional domains of a potential oncoprotein, cell migration inducing hyaluronidase 2 (CEMIP2), evaluate its expression levels and roles in colorectal cancer (CRC), and develop an aptamer-based nanoparticle for targeted therapy. Data mining on TCGA identified that CEMIP2 might play oncogenic roles in CRC. In a local cohort, CEMIP2 mRNA levels significantly stepwise increase in CRC patients with higher stages, and high CEMIP2 confers worse disease-free survival. In addition, CEMIP2 mRNA levels significantly correlated to hyaluronan levels in sera from CRC patients. Deletion mapping identified that CEMIP2 containing G8 and PANDER-like domains preserved hyaluronidase activity and oncogenic roles, including cell proliferation, anchorage-independent cell growth, cell migration and invasion, and human umbilical vein endothelial cell (HUVEC) tube formation in CRC-derived cells. A customized monoclonal mouse anti-human CEMIP2 antibody probing the PANDER-like domain (anti-289307) counteracted CEMIP2-mediated carcinogenesis in vitro. Cell-SELEX pinpointed an aptamer, aptCEMIP2(101), specifically interacted with the full-length CEMIP2, potentially involving its 3D structure. Treatments with aptCEMIP2(101) significantly reduced CEMIP2-mediated tumorigenesis in vitro. Mesoporous silica nanoparticles (MSN) carrying atpCEMIP2(101) and Dox were fabricated. Dox@MSN, MSN-aptCEMIP2(101), and Dox@MSN-aptCEMIP2(101) significantly suppressed tumorigenesis in vitro compared to the Mock, while Dox@MSN-aptCEMIP2(101) showed substantially higher effects compared to Dox@MSN and MSN-aptCEMIP2(101) in CRC-derived cells. Our study identified a novel oncogene and developed an effective aptamer-based targeted therapeutic strategy.

Performance of the Fecal Immunochemical Test in Detecting Advanced Colorectal Neoplasms and Colorectal Cancers in People Aged 40-49 Years: A Systematic Review and Meta-Analysis.

BACKGROUND: The incidence of early-onset colorectal cancer (CRC) is increasing. Many guidelines recommend initiating screening at 45 years. This study investigated the detection rate of advanced colorectal neoplasm (ACRN) by using fecal immunochemical tests (FITs) in individuals aged 40-49 years. METHODS: PubMed, Embase, and Cochrane Library databases were searched from inception to May 2022. The primary outcomes were the detection rates and positive predictive values of FITs for ACRN and CRC in people aged 40-49 (younger age group) and ≥50 years (average risk group). RESULTS: Ten studies with 664,159 FITs were included. The FIT positivity rate was 4.9% and 7.3% for the younger age and average risk groups, respectively. Younger individuals with positive FIT results had significantly higher risks of ACRN (odds ratio [OR] 2.58, 95% confidence interval [CI] 1.79-3.73) or CRC (OR 2.86, 95% CI 1.59-5.13) than did individuals in the average-risk group, regardless of FIT results. Individuals aged 45-49 years with positive FIT results had a similar risk of ACRN (OR 0.80, 95% CI 0.49-1.29) to that of people aged 50-59 years with positive FIT results, although significant heterogeneity was observed. The positive predictive values of the FIT were 10-28.1% for ACRN and 2.7-6.8% for CRC in the younger age group. CONCLUSION: The detection rate of ACRN and CRC based on FITs in individuals aged 40-49 years is acceptable, and the yield of ACRN might be similar between individuals aged 45-49 and 50-59 years. Further prospective cohort and cost-effective analysis are warranted.

A phase Ib/II trial of PEP503 (NBTXR3, radioenhancer) with radiotherapy and chemotherapy in patients with rectal cancer.

Aims: To investigate the safety profile, dose-limiting toxicity and antitumor activity of PEP503 (NBTXR3) nanoparticles with radiotherapy and concurrent chemotherapy in patients with locally advanced or unresectable rectal cancer. Methods: Patients will receive a single intratumoral injection of the nanoparticles, followed by radiotherapy and intravenous infusion of fluorouracil or oral capecitabine concurrently. In phase Ib (escalation phase, 3 + 3 design), volume escalation is based on the tumor volume of 5, 10, 15 and 22% of total baseline tumor volume. In phase II (expansion phase), 18 additional patients will be enrolled. Discussion: This study will be the first prospective, open-label, single-arm, nonrandomized study to investigate the efficacy and safety profile of PEP503 (NBTXR3) nanoparticles with radiotherapy and chemotherapy in these patients. Trial registration number: NCT02465593 (ClinicalTrials.gov).

Preoperative concurrent chemoradiotherapy is the standard treatment for patients with locally advanced rectal cancer. PEP503 (NBTXR3) has radioenhancement properties. Therefore, the dose per fraction during radiotherapy could be reduced, and the same therapeutic efficacy could be retained when PEP503 (NBTXR3) nanoparticles are used during radiotherapy. This study reveals the protocol of a phase Ib/II study to investigate the safety profile, dose-limiting toxicity and antitumor activity of PEP503 (NBTXR3) nanoparticles with radiotherapy combined with concurrent chemotherapy in patients with locally advanced or unresectable rectal cancer.

Unknown­primary neuroendocrine neoplasms diagnosed by short­acting somatostatin test: Case series in one institution.

Neuroendocrine neoplasms (NENs) are a rare heterogeneous group of neoplasms that arise from neuroendocrine cells. Unknown-primary NENs (UP-NENs) are particularly challenging to diagnose and treat. Techniques such as immunohistochemical stains, functional imaging studies, and molecular cancer classifier assays may help clinicians identify the origin of a tumor. However, numerous medical facilities lack the necessary medical equipment, such as functional imaging scanning, to provide patients with a complete primary tumor survey. Even these tests are not enough to determine the original tumor in some cases. The present case series described the diagnosis and treatment outcomes of patients with UP-NEN in a single institution. The medical records of four patients treated between November 2012 and January 2022 were retrospectively reviewed and clinical symptoms, diagnostic methods, image findings and treatment modalities were considered. All patients were diagnosed having functional UP-NENs by using a short-acting somatostatin test. These patients were treated with long-acting release somatostatin analogs along with a positive result. Short-acting somatostatin is an alternatively simple method to determine if a patient has UP-NENs that are functional or expresses somatostatin receptors in the absence of imaging scanning.

Efficacy of concurrent radiotherapy in patients with locally advanced rectal cancer and synchronous metastasis receiving systemic therapy.

Background: Neoadjuvant chemoradiotherapy followed by total mesorectal excision is the standard treatment for patients with nonmetastatic locally advanced rectal cancer (LARC). However, for patients with LARC and synchronous metastasis, the optimal treatment strategy and sequence remain inconclusive. In the present study, we evaluated the efficacy and safety of concurrent radiotherapy in patients with de novo metastatic rectal cancer who received chemotherapy and targeted therapy. Methods: We retrospectively reviewed the data of 63 patients with LARC and synchronous metastasis who received intensive therapy at the study hospital between April 2015 and November 2018. The included patients were divided into two groups: RT-CT, those who received systemic chemotherapy with targeted therapy and concurrent radiotherapy (for primary rectal cancer), and CT, those who received only systemic chemotherapy with targeted therapy. Results: Treatment response was better in the RT-CT group than in the CT group. The rate of primary tumor resection (PTR) was higher in the RT-CT group than in the CT group (71.4% and 42.9%, respectively; P = .0286). The RT-CT group exhibited considerably longer local recurrence-free survival (P = .0453) and progression-free survival (PFS; from 13.3 to 22.5 months) than did the CT group (P = .0091); however, the groups did not differ in terms of overall survival (OS; P = .49). Adverse events were almost similar between the groups, except frequent diarrhea, the prevalence of which was higher in the RT-CT group than in the CT group (59.5% and 23.8%, respectively; P = .0075). Conclusions: In the era of biologics, radiotherapy may increase the resectability of primary rectal tumors, reducing the risk of locoregional failure and prolonging PFS. Concurrent pelvic radiotherapy may not substantially improve OS, which is indicated by metastasis. Hence, the resection of the distant metastases may be essential for improving long-term OS. To further determine the efficacy of concurrent radiotherapy, additional prospective, randomized studies must combine preoperative pelvic radiotherapy with PTR and metastectomy to treat patients with stage IV LARC.

Identifying and clinically validating biomarkers for immunotherapy in colorectal cancer.

INTRODUCTION: Colorectal cancer (CRC) is a leading cause of death. For three decades, chemotherapy with or without targeted therapy (provided before or after tumor resection surgery) has been the standard treatment for patients with CRC. Biomarkers are key tools for performing early detection, prognostication, and survival and treatment response predictions. Notably, immune checkpoint inhibitors (ICIs) have transformed prognoses for solid tumors (including CRC). AREA COVERED: Although immunotherapy has developed considerably, it is only effective for a small number of microsatellite instability-high (MSIH) cancer cases; such cases represent only 5% of metastatic CRC (mCRC) cases, which are characterized by an immune-inflamed microenvironment that can be rewired against cancer cells through ICI administration. Immunotherapy research is gradually uncovering the mechanism underlying immune resistance in patients with CRC and discovering new biomarkers. For example, studies have clinically validated the associations of deficient mismatch repair system/microsatellite instability, tumor mutation burden, programmed death ligand 1 expression, and polymerase epsilon with CRC in patients undergoing immunotherapy. EXPERT OPINIONS: Clinical trials documenting the effect of immune checkpoints were performed to produce long-lasting effects for patients with mCRC. Consequently, therapeutic decision-making models are further refined by the inclusion of powerful molecular biomarkers in patients with CRC.

MicroRNAs as Predictive Biomarkers in Patients with Colorectal Cancer Receiving Chemotherapy or Chemoradiotherapy: A Narrative Literature Review.

Colorectal cancer (CRC) is one of the most common malignancies and is associated with high mortality rates worldwide. The underlying mechanism of tumorigenesis in CRC is complex, involving genetic, lifestyle-related, and environmental factors. Although radical resection with adjuvant FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin) chemotherapy and neoadjuvant chemoradiotherapy have remained mainstays of treatment for patients with stage III CRC and locally advanced rectal cancer, respectively, the oncological outcomes of these treatments are often unsatisfactory. To improve patients' chances of survival, researchers are actively searching for new biomarkers to facilitate the development of more effective treatment strategies for CRC and metastatic CRC (mCRC). MicroRNAs (miRs), small, single-stranded, noncoding RNAs, can post-transcriptionally regulate mRNA translation and trigger mRNA degradation. Recent studies have documented aberrant miR levels in patients with CRC or mCRC, and some miRs are reportedly associated with chemoresistance or radioresistance in CRC. Herein, we present a narrative review of the literature on the roles of oncogenic miRs (oncomiRs) and tumor suppressor miRs (anti-oncomiRs), some of which can be used to predict the responses of patients with CRC to chemotherapy or chemoradiotherapy. Moreover, miRs may serve as potential therapeutic targets because their functions can be manipulated using synthetic antagonists and miR mimics.

Clinicopathological Features and Oncological Outcomes of Early and Late Recurrence in Stage III Colorectal Cancer Patients after Adjuvant Oxaliplatin-Based Therapy.

Aims: An adjuvant oxaliplatin-based regimen is the standard of care for patients with stage III colorectal cancer (CRC). Few reports have compared the clinicopathological features and oncological outcomes of such treatment between patients with early (≤1 year) and late recurrence (>1 year). Methods: Between January 2012 and December 2019, CRC recurred in 128 (24.1%) of 531 patients with consecutive stage III CRC after they received curative resection and an adjuvant oxaliplatin-based regimen. The clinicopathological features and oncological outcomes of the 128 patients were analyzed retrospectively. Results: The median follow-up period after the first chemotherapy cycle was 35.0 months (range, 7-100.9), and the median recurrence time was 16.1 months. Forty-seven patients (36.7%) had an early recurrence and eighty-one patients (63.3%) had a late recurrence. Compared with patients with late recurrence, those with early recurrence were mostly younger (median: 58 vs. 64 years, p=0.009), had less oxaliplatin-based therapy cycles (median: 8 vs. 12 cycles, p < 0.001), and had a shorter overall survival time (median: 23.3 vs. 39.7 months, p < 0.001). The area under the curve of patient age and chemotherapy cycles for predicting early recurrence was 0.629 and 0.705 (p=0.015 and p < 0.001), respectively. The receiver operating characteristic curve analysis demonstrated that the cutoff level for patient age was 57 years and the number of chemotherapy cycles was 8. A multivariate analysis revealed that patient age ≤57 years and oxaliplatin-based therapy ≤8 cycles were independent risk factors for early recurrence (odds ratio (OR) = 3.049, p=0.022; OR = 4.995, p=0.002). These factors were associated with an approximately 77.8% risk of recurrence within 1 year, compared with the 21.5% risk associated with patient age >57 years and oxaliplatin-based therapy >8 cycles (p = 0.003). Conclusion: Patients with early recurrence had poorer survival than those with late recurrence. If >8 cycles of oxaliplatin-based therapy can be administered without disease progression, then patients with stage III CRC would have a lower risk of early recurrence.

Survival benefit of metastasectomy in first-line cetuximab therapy in patients with RAS wild-type metastatic colorectal cancer: a nationwide registry.

This multicenter study aimed to explore the survival benefit of metastasectomy by first-line cetuximab-based chemotherapy in real-world patients with RAS wild-type metastatic colorectal cancer (mCRC). The primary endpoints were overall survival (OS) and progression-free survival (PFS). The secondary endpoints included objective response rate (ORR), disease control rate (DCR), and metastasectomy rate. The exploratory endpoint was the optimal treatment cycle for better OS and PFS. Receiver operating characteristic curve with the area under curve (AUC) was used to identify the optimal cut-off cycle for survival outcomes. A total of 758 mCRC patients were enrolled in this study, with a median OS of 35.1 months, median PFS of 14.6 months, and metastasectomy rate of 21.4%. Left-sided mCRC had a significantly higher DCR (88.9% vs. 73.1%, P<0.001) and better OS (36.4 vs. 19.6 months, P<0.001). There were no significant differences in PFS and metastasectomy rate between left-sided and right-sided mCRC. However, mCRC patients who underwent metastasectomy over the course of treatment had better OS (54.9 vs. 28.6 months, P<0.001) and PFS (21.0 vs. 13.1 months, P<0.001) than those who did not. Notably, right-sided mCRC who benefited from first-line cetuximab-based chemotherapy to underwent metastasectomy also had favorable outcomes, on a par with left-sided mCRC. The optimal treatment cycle was 14 cycles (AUC: 0.779, P<0.001). Patients who received ≥14 cycles had higher metastasectomy rates (27.5% vs. 13.5%, P<0.001), favorable OS (42.6 vs. 23.4 months, P<0.001) and PFS (18.1 vs. 8.6 months, P<0.001), and, importantly, had comparable adverse events compared with patients who received <14 cycles of treatment. Patients who underwent metastasectomy after or during first-line cetuximab therapy have an improved OS in both left-sided and right-sided mCRC. Furthermore, patients receive ≥14 cycles of treatment whenever possible to achieve a higher likelihood of metastasectomy was associated with favorable survival outcomes.

Comprehensive Review of Biomarkers for the Treatment of Locally Advanced Colon Cancer.

Despite the implementation of global screening programs, colorectal cancer (CRC) remains the second leading cause of cancer-related deaths worldwide. More than 10% of patients with colon cancer are diagnosed as having locally advanced disease with a relatively poor five-year survival rate. Locally advanced colon cancer (LACC) presents surgical challenges to R0 resection. The advantages and disadvantages of preoperative radiotherapy for LACC remain undetermined. Although several reliable novel biomarkers have been proposed for the prediction and prognosis of CRC, few studies have focused solely on the treatment of LACC. This comprehensive review highlights the role of predictive biomarkers for treatment and postoperative oncological outcomes for patients with LACC. Moreover, this review discusses emerging needs and approaches for the discovery of biomarkers that can facilitate the development of new therapeutic targets and surveillance of patients with LACC.

Enrichment of Prevotella intermedia in human colorectal cancer and its additive effects with Fusobacterium nucleatum on the malignant transformation of colorectal adenomas.

BACKGROUND: Owing to the heterogeneity of microbiota among individuals and populations, only Fusobacterium nucleatum and Bacteroides fragilis have been reported to be enriched in colorectal cancer (CRC) in multiple studies. Thus, the discovery of additional bacteria contributing to CRC development in various populations can be expected. We aimed to identify bacteria associated with the progression of colorectal adenoma to carcinoma and determine the contribution of these bacteria to malignant transformation in patients of Han Chinese origin. METHODS: Microbiota composition was determined through 16S rRNA V3-V4 amplicon sequencing of autologous adenocarcinomas, adenomatous polyps, and non-neoplastic colon tissue samples (referred to as "tri-part samples") in patients with CRC. Enriched taxa in adenocarcinoma tissues were identified through pairwise comparison. The abundance of candidate bacteria was quantified through genomic quantitative polymerase chain reaction (qPCR) in tissue samples from 116 patients. Associations of candidate bacteria with clinicopathological features and genomic and genetic alterations were evaluated through odds ratio tests. Additionally, the effects of candidate bacteria on CRC cell proliferation, migration, and invasion were evaluated through the co-culture of CRC cells with bacterial cells or with conditioned media from bacteria. RESULTS: Prevotella intermedia was overrepresented in adenocarcinomas compared with paired adenomatous polyps. Furthermore, co-abundance of P. intermedia and F. nucleatum was observed in tumor tissues. More notably, the coexistence of these two bacteria in adenocarcinomas was associated with lymph node involvement and distant metastasis. These two bacteria also exerted additive effects on the enhancement of the migration and invasion abilities of CRC cells. Finally, conditioned media from P. intermedia promoted the migration and invasion of CRC cells. CONCLUSION: This report is the first to demonstrate that P. intermedia is enriched in colorectal adenocarcinoma tissues and enhances the migration and invasion abilities of CRC cells. Moreover, P. intermedia and F. nucleatum exert additive effects on the malignant transformation of colorectal adenomas into carcinomas. These findings can be used to identify patients at a high risk of malignant transformation of colorectal adenomas or metastasis of CRC, and they can accordingly be provided optimal clinical management.