Optimal prognostic stratification for colorectal liver metastases (CRLM) patients undergoing surgery with neoadjuvant therapy (NAT) remains elusive. This study aimed to develop and validate dual-time-point radiomic models for CRLM prognosis prediction using pre- and post-NAT imaging features.

Radiomic features were extracted from four MRI sequences in 100 cases of CRLM patients who underwent NAT and radical resection. RAD scores were generated, and clinical/pathologic variables were incorporated into uni- and multivariate Cox regression analyses to construct prognosis models. Time-ROC, time-C index, decision curve analysis (DCA), and calibration curves assessed the predictive performance of Fong score and pre- and post-NAT models for overall survival (OS) and disease-free survival (DFS) in a testing set.

The final models included four variables for OS and three variables for DFS. The post-NAT models outperformed the pre-NAT models in time-ROC, time-C index, calibration, and DCA analysis, except for the 1-year DFS area under the curve (AUC). The Fong score models underperformed. The post-NAT OS RAD score effectively stratified patients into prognostic subgroups.

The radiomic models incorporating pre- and post-NAT MRI features and clinical/pathologic variables effectively stratified CRLM patients prognositically. The post-NAT models demonstrated superior performance.

An increasing number of patients with metastatic colorectal cancer (mCRC) have achieved no evidence of diseases (NED) status after surgery or other treatments. However, the latest guidelines for colorectal cancer do not recommend an appropriate treatment for patients with mCRC who achieve NED status. Capecitabine metronomic chemotherapy has the advantages of significant efficacy and minimal adverse reactions, it is a potential effective method for maintenance treatment for mCRC, but no RCTs have been reported. Therefore, we designed a randomized controlled trial to evaluate the efficacy and safety of capecitabine metronomic chemotherapy for mCRC patients who achieve NED.

This study is a prospective, randomized controlled study that evaluates the efficacy and safety of capecitabine metronomic chemotherapy for patients with mCRC who achieve NED status. 240 eligible participants will be randomly assigned to either a capecitabine metronomic chemotherapy group or a "watch and wait" group at a 1:1 allocation ratio. Eligible patients diagnosed with stage IV mCRC, both the primary tumor and the metastases, are those who have achieved R0 resection (or complete destruction by ablation) and reached NED. Participants who are enrolled in the capecitabine group will receive capecitabine (500 mg/m2 body surface area twice daily) for 2 years. Meanwhile, those who are assigned to the control group will receive regular imaging examination and follow-up only. All participants will follow up for 1 year after receiving 2 years of intervention. The primary outcomes will be disease-free survival (DFS) from randomization, stratified by preoperative chemotherapy, metastatic organs, number of metastases, lenght of previous systemic treatment, response to previous chemotherapy. Secondary outcomes will include overall survival (OS), 1-year,2-year,3-year survival rate and adverse reactions.

As a potentially effective treatment, low-dose capecitabine metronomic chemotherapy has been explored in clinical practice. The results of this trial will provide evidence on the efficacy and safety of capecitabine metronomic chemotherapy for patients with mCRC who have reached NED status.

Chinese Clinical Trial Registry (ChiCTR2100047149, protocol version number F2.0).

Surgical removal of metastasized paraaortic lymph nodes (PALNs) can prolong the survival of certain patients with colorectal cancer (CRC). However, the role of postoperative chemotherapy in such patients remains unknown.

This multicenter retrospective study examined 97 patients with PALN metastasis from CRC who underwent surgical resection at 36 centers in Japan between 2010 and 2015. On the basis of adjuvant chemotherapy (AC) after the lymphadenectomy, patients were classified into non-AC and AC groups (27 and 70 patients, respectively). After the exclusion of patients receiving irinotecan, the latter group was further categorized into 5-fluorouracil (5-FU) and oxaliplatin (L-OHP) subgroups (14 and 52 patients, respectively) according to the use of L-OHP. Background characteristics and postoperative survival were compared among the groups.

Marked differences were not seen in background characteristics, except for neoadjuvant treatment, between the non-AC and AC groups. The AC group exhibited better recurrence-free survival (RFS; p = 0.009) and overall survival (OS; p = 0.040 by the Wilcoxon test) than the non-AC group. However, RFS and OS of the 5-FU group did not differ from those of the L-OHP group (p = 0.73 and p = 0.92 by the Wilcoxon test, respectively).

AC may be associated with improved prognosis of patients after the removal of PALN metastasis from CRC, but L-OHP did not offer additional survival benefits. Prospective studies comparing non-AC with 5-FU- and L-OHP-based AC are needed to confirm these findings.

Monocarboxylate transporter 4 (MCT4) is a novel biomarker related to the level of immune cell infiltration, but its impact on tumor immune microenvironment (TIME) of colorectal liver oligometastases (CLO) remains unclear. The aim of this study was to assess MCT4 expression in primary tumor and liver oligometastases, investigate its impact on immune cell infiltration and its prognostic value for CLO patients undergoing liver resection.

We retrospectively selected 135 CLO patients who underwent curative liver resection between June 1999 and December 2016, and samples included 74 primary tumor tissues and 122 liver metastases. Immunohistochemistry (IHC) was performed to detect MCT4 expression in paraffin-embedded specimens and tyramine signal amplification (TSA) was used to detect the density of tumor-infiltrating lymphocytes, including CD3 + , CD8 + and Foxp3 + . Recurrence-free survival (RFS) and overall survival (OS) were analyzed using the Kaplan-Meier method and log-rank test, and independent prognostic factors were identified with Cox regression modeling.

Survival analysis indicated that CLO patients with low MCT4 expression had better 3-year RFS and 3-year OS rates than those with high MCT4 expression. Multivariate analysis indicated that high MCT4 expression was independently associated with poor RFS and OS. High MCT4 expression was associated with a lower number of intratumoral CD3 + /CD8 + T cells and was associated with higher Foxp3 + T cells infiltration. Patients with low MCT4 expression and high levels of differential immune infiltration had longer survival.

MCT4 overexpression was associated with an unfavorable prognosis in patients with CLO and MCT4 expression level had an impact on intratumoral immune infiltration degree. A novel parameter that combined MCT4 expression level and differential immune infiltration level was constructed to stratify patients with CLO into different risk groups.

In Japan, immunohistochemistry for mismatch repair (MMR) proteins targeted at stage II and III colorectal cancers (CRCs) has been covered by national insurance since October, 2022. This study aimed to clarify the long-term outcomes of patients with stage II and III CRCs receiving postoperative adjuvant chemotherapy based on their MMR status.

The outcomes of 640 patients who underwent radical surgery for stage II and III CRCs were analyzed retrospectively.

Deficient MMR (dMMR) was diagnosed in 41 (13.3%) patients with stage II and 28 (9.1%) patients with stage III CRC. The overall survival and recurrence rates were not significantly different between the patients with stage II and those with stage III CRC. The risk factors for recurrence among those with stage II CRC were tumors on the left side, T4 disease, and the presence of BRAF wild type. The recurrence rates were lower in the stage II CRC patients with sporadic dMMR than in those with suspected Lynch syndrome (LS). The first site of recurrence was more frequently the peritoneum or distant lymph node in patients with dMMR.

Stage II CRC patients with sporadic dMMR were found to have a very good prognosis. On the other hand, peritoneal dissemination or distant lymph node metastasis tended to develop in patients with dMMR.

The benefit of neoadjuvant chemotherapy (NAC) in patients with resectable colorectal liver metastasis (CRLM) is debatable. This study aimed to establish a definition of biologically borderline resectable CRLM based on early surgical failure.

One hundred forty-two patients who underwent upfront surgery for resectable CRLM were examined. Potential predictors of early surgical failure were investigated to establish a definition of biologically borderline resectable CRLM. The impact of NAC on overall survival (OS) in patients with borderline resectable CRLM was examined, as were predictors of OS.

Extrahepatic lesions (p < 0.01) and tumor ≥ 30 mm with carcinoembryonic antigen (CEA) concentration ≥ 20 ng/mL (p = 0.02) were independent predictors of early surgical failure. Borderline resectable CRLM was defined as extrahepatic lesions or tumor size ≥ 30 mm with CEA concentration ≥ 20 ng/mL. Fifty-eight patients had borderline resectable CRLM. Three-year OS was significantly higher in borderline resectable CRLM patients who received NAC than in those who did not (71.8% vs. 52.7%) and 5-year survival was also significantly higher in this group (62.8% vs. 25.5%).

We have proposed a simple definition of biologically borderline resectable CRLM based on early surgical failure. NAC could be a good indication for patients who met the definition.

Patients with colorectal cancer liver metastases have long represented a unique and thoroughly investigated population. Nevertheless, the optimal management of these is still controversial with a number of open questions which are only partially addressed by available studies and existing guidelines. The European Organisation for Research and Treatment of Cancer (EORTC) Gastrointestinal Tract Cancer Group (GITCG) sought to fill this knowledge gap and promoted the development of a European consensus on this subject. By using the Delphi methodology and leveraging a multidisciplinary team of 43 international experts, including gastrointestinal oncologists, hepatobiliary surgeons, interventional radiologists, radiation oncologists, radiologists, nuclear medicine physicians and pathologists from 12 European countries, 34 practical recommendations and two consensus statements were proposed. These cover varying aspects of the optimal management of colorectal cancer liver metastases such as baseline imaging, selection criteria for liver-directed therapies, treatment strategies, assessment of treatment response, follow-up, care delivery, clinical research and future perspectives. This roadmap document is intended to complement national and international guidelines, and to provide practical guidance for clinicians and multidisciplinary teams, ultimately promoting practice standardisation, optimal management and better patient outcomes across Europe. Also, it provides a unique opportunity to highlight grey areas and unmet needs, and to give a strategic direction to future research in the field by identifying topics where there is no consensus among experts.

Anastomotic leakage (AL) is one of the most serious clinical complications in digestive tract reconstruction (DTR) surgery, and it is currently hypothesized that this may be related to insufficient anastomotic blood supply. Thus, Therefore, we aimed to assess the ability of tissue oxygen saturation(StO2) as a measure to evaluate anastomotic blood supply.

A comprehensive literature search was performed using Embase, PubMed and Cochrane Library. StO2 was used as an evaluation index of anastomotic blood supply after DTR to analyze the potential association between this index and the occurrence of AL in the postoperative period.

A total of eleven articles involving 867 participants were included in this systematic review and meta-analysis. After pooling the standardized mean difference (SMD) and 95% confidence intervals (Cls), low StO2 was found to be an independent risk factor for AL (P < 0.00001; 95%CI: 1.02 [0.53-1.51]). The mean StO2 in the AL group (62.3%) was significantly lower than that in the non-AL group (74.3%); AL incidence increased with the reduction of StO2 to a certain value to 201.8% and 338.1% respectively.

Oxygen saturation index can be utilized in DTR to accurately and quantitatively evaluate the anastomotic blood supply to reduce the probability of postoperative AL.

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) enable effective management of colorectal and appendiceal peritoneal metastases (CAPM) despite high morbidity. This study aimed to evaluate the role of repeat diagnostic laparoscopy (rDL) after systemic ± intraperitoneal chemotherapy in the management of initially unresectable CAPM.

This retrospective cohort study included 70 consecutive patients with CAPM who underwent initial diagnostic laparoscopy (iDL). Patients with inoperable or equivocal CAPM underwent chemotherapy followed by rDL to assess the treatment response and possibility of conversion to CRS and HIPEC.

Cytoreductive surgery was deemed feasible for 29 patients and unlikely or equivocal for 41 patients based on iDL. Of the 29 resectable patients, 24 successfully underwent CRS and HIPEC after neoadjuvant chemotherapy. Among the 41 patients initially considered unresectable, 16 were deemed operable based on rDL after chemotherapy, and CRS and HIPEC were achieved for 14 patients (conversion). The median peritoneal cancer index was significantly reduced after chemotherapy for the 14 "conversion" patients, from 16 based on iDL to 11 based on rDL (p < 0.05). The conversion rate was 34% (14/41), with a 5-year survival rate of 14%. Treatment with CRS and HIPEC was achieved for 38 of 45 patients deemed operable based on either iDL or rDL (worst-case estimated positive predictive value, 84%).

Diagnostic laparoscopy is useful in predicting the likelihood of achieving CRS for patients with CAPM. Despite inoperability based on iDL, patients should be considered for rDL after chemotherapy to assess the possibility of conversion to CRS and HIPEC.

There is still no consensus as to whether patients with upfront resectable synchronous colorectal liver metastases (sCRLM) should receive neoadjuvant treatment prior to liver surgery. Two randomized controlled trials have assessed the role of peri-operative chemotherapy in sCRLM; neither have shown a survival benefit in the neoadjuvant group. The aim of this population-based study was to examine overall survival in patients treated with neoadjuvant chemotherapy and hepatectomy compared to patients who had upfront surgery.

This is a retrospective observational study between 2009 and 2017 containing data extracted from two Swedish national registries. Descriptive statistics and Cox regression analyses were employed.

In total, 2072 patients with sCRLM were treated with liver surgery between 2009 and 2017. A majority (n = 1238, 60%) were treated with neoadjuvant chemotherapy, and 834 patients (40%) had upfront surgery. Patients in the upfront surgery group were older (median age 70 compared to 65 years, p ≤ 0.001). Median overall survival in the upfront surgery group was 26 months (95% CI 23-29 months) compared to 57 months (95% CI 42-48 months) in the neoadjuvant group, log rank p ≤ 0.001. In the multivariable Cox regression analysis, age ≥ 70 years (HR 1.46, 95% CI 1.25-1.70), T category of primary cancer (HR 1.41, 95% CI 1.09-1.84), lymphatic spread of primary cancer (HR 1.68, 95% CI 1.41-1.99), and number of liver metastases (six or more metastases resulted in HR 2.05, 95% CI 1.38-3.01) negatively influenced overall survival. By contrast, adjuvant therapy was protective (HR 0.80, 95% CI 0-69-0.94), whereas neoadjuvant treatment compared to upfront surgery did not influence overall survival (HR 1.04, 95% CI 0.86-1.26).

Neoadjuvant treatment in sCRLM did not confer a survival benefit compared to upfront surgery.

We aimed to define borderline resectable colorectal liver metastases (CRLM) based on the analysis of risk factors for early surgical failure and investigate the efficacy of neoadjuvant chemotherapy in these patients.

This was a retrospective analysis of a multi-institutional cohort of patients diagnosed with technically resectable CRLM. Early surgical failure within 6 months of liver surgery was defined as ESF6. We classified CRLM into three grades (A, B, and C) according to the definition of the Japanese Society for Cancer of the Colon and Rectum.

Among the 249 patients with technically resectable CRLM, 46 (18.5%) developed ESF6. The survival rate of these patients was significantly lower than that of the patients without ESF6. In the multivariate analysis of synchronous CRLM patients, no neoadjuvant chemotherapy, Grade B/C, and Charlson comorbidity index ≥ 3 were independent predictors of ESF6. Among patients with synchronous and Grade B/C CRLM, ESF6 rates, surgical failure-free survival, and overall survival in the neoadjuvant chemotherapy group were significantly better relative to the upfront surgery group.

Patients with synchronous and Grade B/C CRLM are at a high risk of early surgical failure, have a poor long-term prognosis, and can be defined as borderline resectable and good candidates for neoadjuvant chemotherapy.

Colorectal cancer most commonly metastasizes to the liver. While various treatment strategies have been developed, surgical management of these patients has vital implications on the prognosis and survival of this group of patients. There remains a need for a consensus guideline regarding the surgical evaluation and management of patients with colorectal liver metastases (CRLM).

This review article is a consensus guideline established by the members of the AHPBA Professional Standards Committee, as an amalgamation of existent literature and a guide to surgeons managing this complex disease.

These guidelines reports the benefits and shortcomings of various diagnostic modalities including imaging and next-generation sequencing in the management of patients with CRLM. While surgery has established survival benefits in patients with resectable disease, this report notes the importance of treatment sequencing with non-surgical modalities as well as between colon and liver resection. Finally, the guidelines address the various treatment modalities for patients with unresectable disease, that may have significant impact on survival.

CRLM is a complex diagnosis which warrants multidisciplinary approach with early surgical involvement in both assessment and management of the disease, to optimize patient outcomes and survival.

Standard adjuvant treatment of stage III colon cancer (CC) is fluoropyrimidine with oxaliplatin. Recently, stage III was subdivided into low-risk (T1-3, N1) and high-risk (T4 and/or N2), with the benefit of adding oxaliplatin varying across these substages. In this study, we aimed to assess the impact of oxaliplatin on survival outcomes in subdividing stage III CC patients based on T and N staging.

A total of 4942 stage III CC patients were pooled from the three randomized pivotal trials of oxaliplatin. Kaplan-Meier curves, Cox models stratified by study, and interaction tests were used to assess the oxaliplatin effect across subgroups based on T and N stages. The primary endpoint was overall survival (OS).

The prevalence of tumor stages was T1-2 12.4%, T3 74.4%, and T4 13.1%; nodal stages were N1 64.7% and N2 35.3%. A significant OS benefit from oxaliplatin was seen only in T3 (5-year OS = 77.2% versus 73.0%, P < 0.001): T3N1 (hazard ratio 0.72, 95% confidence interval 0.62-0.85, P < 0.001) and T3N2 (hazard ratio 0.81, 95% confidence interval 0.69-0.95, P = 0.010). No benefit was observed for T1-2 (5-year OS = 87.8% versus 88.7%, P = 0.644) or T4 patients (5-year OS = 62.6% versus 60.2%, P = 0.648). Subgroup analysis revealed a significant interaction between T stage and the effect of oxaliplatin treatment on OS, whereas no such interaction was observed for N stage.

Our analysis revealed that oxaliplatin-based chemotherapy offers a significant survival benefit in stage III CC patients with T3 tumors. In contrast, no survival benefit was observed for T1-2 or T4 patients. These results suggested that T stage plays a more crucial role than N stage in predicting treatment benefit, highlighting the need for tailored treatment strategies based on tumor characteristics.

Colorectal cancer (CRC) frequently metastasizes to the liver and lungs, leading to poor prognosis. Advances in chemotherapy, minimally invasive surgery, and perioperative care have expanded adjuvant chemotherapy (AC) regimens and eligibility for AC. However, the impact of AC after curative resection of distant metastases on recurrence and prognosis remains uncertain. This study evaluated the role of AC in CRC liver and lung metastases, focusing on cases with curative resection based on the latest studies published in the past five years.

This systematic review followed PRISMA guidelines. Literature searches of Medline and Cochrane Library (2019-2023) identified studies on AC or observation after curative resection of CRC metastases, reporting outcomes such as overall survival (OS) and disease-free survival (DFS). Data analysis was performed using Review Manager and R software, with results expressed as hazard ratios (HR) and 95% confidence intervals (CI).

Seven studies met the eligibility criteria, including one randomized controlled trial and six retrospective studies, encompassing 1580 patients who underwent curative resection (R0) for CRC metastases. This meta-analysis showed a positive trend in OS for the AC group compared to that for the surgery-alone group (HR 0.86, 95% CI: 0.73-1.01; p = 0.06), but the difference was insignificant. AC significantly improved DFS (HR 0.81, 95% CI: 0.66-0.99; p = 0.04). Subgroup analysis indicated that AC significantly improved DFS and tended to improve OS for liver metastasis. In contrast, AC did not improve OS in cases of lung metastasis.

This meta-analysis suggests that AC demonstrated significant positive effects on DFS. Moreover, AC could contribute to improvements in OS. These findings, supported by the latest research, reinforce the recommendation of AC as a valuable strategy for improving both recurrence and survival outcomes in patients with curatively resected distant CRC metastases.

Patients with colorectal liver-only metastases (CRLM) eligible for local treatment (resection/ablation) do not always receive this potentially curative treatment due to the lack of clear resectability criteria and expertise in centres not performing liver surgery. We evaluated the potential value of a liver expert panel in daily practice.

All patients with CRLM starting with systemic treatment in centres not performing liver surgery between 2016 and 2020 were identified in the Netherlands Cancer Registry. A panel of liver surgeons retrospectively re-evaluated patients' imaging for resectability before and two-monthly during systemic treatment.

Sixty-three patients were included from 24 hospitals requiring a total of 544 resectability assessments by individual panel surgeons. The panel considered 18 (29 %) patients to have resectable CRLM before starting systemic treatment, which increased to 43 (68 %) after up to three evaluations. Eighteen (29 %) patients considered resectable by the panel at any time received no local treatment of whom 9 (50 %) were not referred to a liver surgeon.

In non-liver-surgery centres, over a quarter of patients technically eligible for local treatment of initially unresectable CRLM, sometimes mistakenly categorised as such, did not receive this. This stresses the need for liver expert panels in daily practice to increase local treatment rates.

Unresectable recurrence is a critical predictor of outcomes for colorectal cancer patients. We attempted to identify the prognostic factors, especially for unresectable recurrence-free survival (URFS) as a new endpoint, in patients with resectable colorectal liver-only metastasis (CRLOM).

We investigated patients with resectable CRLOM, who underwent an R0 resection for both CRC and CRLOM between January, 2014 and March, 2019 at a single institution. The exclusion criteria were patients who received neoadjuvant treatment, the absence of data for genetic analyses, and the presence of multiple cancers, synchronous CRC, or familial adenomatous polyposis. The prognostic factors were examined retrospectively using data on pre-hepatectomy factors, including primary tumor molecular profiling results.

We analyzed the data of 101 patients who underwent curative-intent surgery for CRLOM. Multivariate analysis revealed that KRAS G12D mutation-positivity (hazard ratio [HR]: 7.69; p < 0.01), RYR2 mutation-positivity (HR: 4.03; p < 0.01), and KRAS G12S mutation-positivity (HR: 3.96; p = 0.03), CA19-9 > 37 U/ml before hepatectomy (HR: 3.62; p < 0.01), and primary tumor pN2 stage (HR: 3.22; p = 0.03) were significant predictors of the URFS.

This is the first study to show that specific KRAS and RYR2 mutations were associated with the URFS.

Approximately 50% of colorectal cancer patients develop liver metastases. Hepatic metastases represent the most common cause of colorectal cancer-related mortality. Metastasectomy, if possible, represents the most effective treatment strategy; 20% of patients will be cured and more than 50% survive at least 5 years. Nuances to treatment planning hinge on whether patients present with resectable disease upfront, whether the future liver remnant is adequate, and whether the primary tumor, if present, is colon versus rectal in origin. This article discusses considerations impacting our approach to patients with colorectal liver metastases and the role for various multimodal treatment options.

Colorectal cancer (CRC) frequently metastasizes to the liver, significantly worsening patient outcomes. While hepatectomy offers the best curative option for colorectal liver metastases (CRLM), margin recurrence remains a major challenge post-surgery. Intraoperative ultrasound (IOUS) aids tumor identification and margin determination, but its limitations in laparoscopic surgery necessitate additional methods. Indocyanine green fluorescence imaging (ICGFI) has emerged as a promising tool for tumor localization and margin assessment in CRLM. However, existing studies lack large cohorts and long-term outcomes. This study evaluates perioperative and long-term results of ICGFI-assisted laparoscopic hepatectomy in CRLM patients.

A retrospective cohort study was performed on CRLM patients who underwent liver resection at our single center. The study population was divided into three groups: the L-ICG group (laparoscopic hepatectomy with ICGFI), the L-Non-ICG group (laparoscopic hepatectomy without ICGFI), and the open group (open liver resection). Robust statistical methods including multiple imputations and inverse probability of treatment weighting (IPTW) were employed to minimize bias.

A total of 340 CRLM patients who underwent hepatectomy were analyzed. The L-ICG group had a higher rate of neoadjuvant therapy and smaller tumor sizes compared to the open group. The L-ICG group also demonstrated shorter operative times, less blood loss, and a higher microscopically margin-negative (R0) resection rate than other two groups. Recurrence occurred in 70% of patients, with 77% being intrahepatic. Margin recurrence was significantly lower in the L-ICG group compared to the L-Non-ICG group (15.3% vs. 45.7%, p = 0.001). Median recurrence-free survival and overall survival did not differ significantly among groups after IPTW adjustment.

ICGFI improves R0 resection rates, perioperative outcomes, and reduces margin recurrence in CRLM patients undergoing laparoscopic hepatectomy, though it does not significantly impact OS or RFS.

The benefit of resection of liver metastases depends on primary diseases. Neuroendocrine tumors are associated with favorable prognosis after resection of liver metastases. Gastric cancer has worse tumor biology, and resection of gastric liver metastases should be performed in selected patients. A multidisciplinary approach is well established for colorectal liver metastases (CLMs). Resection remains the only curative treatment of CLM. Chemotherapy and molecular-targeted therapy have improved survival in unresectable metastatic colorectal cancer. Understanding of the following two strategies, conversion therapy and two-stage hepatectomy, are important to make this patient group to be candidates for curative-intent surgery.

To address the issue that most microsatellite-stable (MSS) and proficient mismatch repair (pMMR) metastatic colorectal cancer (mCRC) patients have minimal response to immunotherapy, this meta-analysis evaluated the efficacy and safety of durvalumab and tremelimumab with concomitant treatment in treating MSS/pMMR metastatic colorectal cancer.

All included trials were prospective studies with a median patient age of 63 years, of which 94.2% were MSS/pMMR mCRC patients, with a male to female ratio of 1.5:1. Based on durvalumab and tremelimumab treatment, one study performed surgical resection on resectable cases, while the other four studies performed radiotherapy or chemotherapy on unresectable cases. Analyses include objective response rate (ORR).etc. for drug activity, overall survival (OS) and progression-free survival (PFS) for therapeutic efficacy, and adverse events (AEs) for safety. The risk of bias was assessed by sensitivity analysis.

5 studies involving 228 patients were included in this meta-analysis. The pooled estimates showed a median OS of 9.26 months, median PFS of 2.53 months, partial response (PR) of 13.6%, stable disease (SD) of 32.8%, ORR of 12.5% and disease control rate (DCR) of 65.4%. AEs were generally low, with pruritus (27.5%), diarrhea (28.8%), and fatigue (53.9%) being the most common, while other AEs occurred at less frequencies.

Durvalumab and tremelimumab with concomitant treatment for MSS/pMMR mCRC patients is relatively effective and safe, which is helpful in addressing the problem of mCRC with MSS/pMMR that has minimal response to immunotherapy.

Perioperative chemotherapy has emerged as a critical component in managing resectable colorectal liver metastases (CRLM), aiming to improve long-term survival, although data supporting its use remains controversial. This narrative review explores the current state of perioperative chemotherapy in patients with resectable CRLM, focusing on its role in different oncological risk categories. The review highlights ongoing controversies, such as optimal patient selection and the role of post- versus preoperative treatment in specific scenarios.

The management of colorectal cancer (CRC) is a complex process. Defining the disease burden, assessing the radiological response and identifying the right time for surgery or other locoregional treatments are crucial factors which can require the involvement of a multidisciplinary tumor board (MDTB) comprising several specialists. This study investigates the impact of MDTB on management of CRC in our institution.

We retrospectively assessed all cases discussed by our MDTB between September 2019 and April 2023. In particular, we collected data concerning radiology, surgery and radiotherapy indication before and after MDTB meetings. The primary endpoint was the overall rate of discrepancy between pre- and post-discussion evaluations.

Our analysis involved 1150 cases. Median age was 64 years (16-90), 629 patients (54.7%) were male and 915 (79.5%) had metastatic disease at the time of the relevant MDTB discussion. After the meetings, 325 treatment decisions were modified, producing an overall discrepancy rate of 28.3%. In particular: (1) of 648 cases discussed for radiological assessment, 156 decisions (24.1%) were altered after a central imaging review; (2) of 327 cases considered for surgical approach, treatment strategy changed in 118 (36.1%); and (3) of the 160 cases discussed regarding radiotherapy, the treatment strategy changed in 51 of them (31.9%).

Our analysis shows significant discrepancies between the radiology and locoregional evaluations from both before and after the MDTB meetings. Our results highlight that the discussions of a MDTB can considerably change the management of CRC, maximizing the treatment strategy.

The Japanese Grade Classification based on the status of pulmonary and mesenteric nodal metastases and the presence of extrapulmonary metastases had a prognostic value in patients with colorectal lung metastases previously. Because the survival of such patients has improved in the era of conversion therapy, this classification needs to be reaudited.

This study reviewed the treatment sequences of 126 colorectal cancer patients with synchronous lung metastases between 2010 and 2022 at our hospital. Patients were divided into Japanese Classification Grade A, B, and C. Prognostic factors for overall survival (OS) were analyzed.

Thirty patients were initially diagnosed with resectable disease. Among these, 6 (35%) of 17 patients who were scheduled to undergo upfront surgery developed unresectable disease. In contrast, 3 (23%) of 13 patients receiving neoadjuvant therapy could not undergo curative resection. Twelve (13%) of 96 patients with initially unresectable metastases underwent conversion to complete resection after systemic therapy. On multivariate analysis, curative resection and H3 (> 5 liver metastases and maximum diameter > 5 cm) at diagnosis were independent prognostic factors, whereas the Japanese Grade Classification was not associated with OS.

Instead of the Japanese classification, a new prognostic classification incorporating H3 should be established.

Decision regarding local treatment of colorectal liver metastases (CRLM) is a multidisciplinary assessment, and liver intervention should be performed when the metastases are deemed resectable. There is no standard biomarker to aid neither this decision nor the postoperative treatment decisions. The present prospective, observational study aimed to investigate the potential clinical utility of a combined tumor-specific and organ-specific methylated circulating DNA assay in the perioperative setting of CRLM.

The study included 56 cases with CRLM. Blood samples were drawn preoperatively and postoperatively. Multiplex methylation analysis of the markers NPY, KANK1, and GAL3ST3 (meth-ctDNA) was performed using droplet digital PCR.

The assay detected preoperative and postoperative meth-ctDNA in 37 % and 46 % of patients, respectively. Patients with negative preoperative meth-ctDNA had a longer median PFS compared to those with positive preoperative meth-ctDNA (HR = 2.2, 95 % CI 1.2-3.9, p < 0.01). In a multivariate analysis, preoperative negative meth-ctDNA was identified as a strong independent predictor of PFS (HR = 3.3, 95 % CI 1.5-7.2, p < 0.01). Similarly, patients with negative postoperative meth-ctDNA had longer median PFS (HR = 3.0, 95 % CI = 1.6-5.6, p < 0.001) and OS (HR = 4.1, 95 % CI 1.9-9.1, p < 0.001) compared to those with positive postoperative meth-ctDNA.

Preoperative meth-ctDNA may serve as an important biomarker to inform the multidisciplinary assessment and treatment planning of CRLM. Negative meth-ctDNA may indicate the optimal timing for liver intervention, whereas positive meth-ctDNA may indicate initiation or re-orientation of chemotherapy, or immediate local intervention. Our results confirm postoperative negative meth-ctDNA as a strong prognostic marker of survival.

Hepatic artery infusion (HAI) chemotherapy, particularly with floxuridine (FUDR), has previously shown effectiveness in improving recurrence-free survival (RFS) in colorectal cancer (CRC) patients with colorectal liver metastases (CRLM). Nonetheless, its adjuvant use alongside modern systemic chemotherapy remains unevaluated.

The HARVEST trial is an open-label, randomized, controlled study conducted from May 2018 to August 2021. CRC patients with resectable primary tumors and CRLM were recruited and randomized to receive standard systemic chemotherapy only (non-HAI group) or in combination with HAI-FUDR (HAI group). However, due to a FUDR manufacturing shortage, the study was terminated early after enrolling 92 patients. The primary endpoint was the 3-year RFS rate, with secondary endpoints including overall survival (OS), liver-specific RFS, and adverse events.

Of the 92 randomized patients, 77 were included in the modified intention-to-treat analysis. Three-year RFS rates were comparable between the HAI (N = 38) and non-HAI (N = 39) groups (31.4 % vs. 34.4 %; P = 0.28). However, improved 1-year RFS and a longer expected five-year OS were observed in the HAI group. While exploratory subgroup analysis suggested potential RFS benefits for patients with multiple liver metastases, RAS/BRAF mutations, and positive postoperative ctDNA methylation, multivariable analysis did not identify these as independent factors. Safety analysis showed comparable chemotherapy-related adverse events, except for a higher occurrence of ALT elevation in the HAI group.

While our study showed no significant difference in three-year RFS, adjuvant chemotherapy intensification with HAI-FUDR is feasible and may offer early benefits in RFS and long-term OS. Nonetheless, a larger sample size is needed for validation and identifying which patient subgroup might benefit from this regimen.

ClinicalTrials.gov: NCT03500874.

Hepatic metachronous oligometastatic nasopharyngeal carcinoma (hmoNPC) exhibits distinct clinical characteristics compared to other types of metastatic NPC. We investigated the optimal therapy for hmoNPC. 160 patients with hmoNPC treated in Sun Yat-sen University Cancer Center between 2010 and 2021 were retrospectively recruited. A total of 56 patients were classified into the local therapy (LT) cohort, 23 into the systemic therapy (ST) cohort and 81 into the combination therapy (LT + ST) cohort. The median PFS was 7.9 months (95% confidence interval [CI]: 4.1-11.9 months) in the LT cohort, 15.5 months (95% CI: 10.5-32.3 months) in the ST cohort, and 31.3 months (95% CI: 20.3 to NA months) in the LT + ST cohort. The median OS was 41.1 months (95% CI: 30.0-54.0 months) in the LT cohort, 50.4 months (95% CI: 41.5 to NA months) in the ST cohort and not reached (NR) (95% CI: 77.3 to NA months) in the LT + ST cohort. Cox analysis was used to construct nomograms to predict patient outcomes. Among patients with no evidence of disease status after LT, the prognosis was significantly better in the LT + ST cohort than LT cohort (median PFS: NR [95% CI: 29.0 to NA months] vs. 20.0 months [95% CI: 10.4 to NA months]). More survival benefits were achieved with platinum-based chemotherapy than oral monotherapy (median PFS: NR [95% CI: 21.7 to NA months] vs. 17.2 months [95% CI: 10.2 to NA months]). Fewer postoperative early progression events were observed in neoadjuvant chemotherapy cohort than in adjuvant chemotherapy cohort (2.78% vs. 18.81%, P = .013). In conclusion, combining neoadjuvant platinum-based chemotherapy and local therapy was the best strategy for patients with hmoNPC.

Contrast-enhanced intraoperative ultrasonography (CE-IOUS) is crucial for detecting colorectal liver metastases (CLM) during surgery. Although artificial intelligence shows potential in diagnostic systems, its application in CE-IOUS is limited.

This study aimed to develop an automatic tumor detection model using Mask region-based convolutional neural network (Mask R-CNN) for CE-IOUS images. CE-IOUS videos of the CLM from 121 patients were collected, generating ground truth data. A total of 2659 images were obtained. Two models were developed: the basic recognition model (BRM), which was trained on CE-mode images, and the subtraction model (SM), which used images created by a subtraction algorithm that highlighted the differences in pixel values between the basic-mode and CE-mode images. The subtraction algorithm focuses on echogenicity differences. These two models were combined into a combination model (CM), which assessed outcomes using the prediction probabilities from both models.

The optimal epochs were determined by the maximum area under the curve (AUC), and the thresholds were calculated accordingly. BRM, SM, and CM achieved 89.4%, 86.6%, and 96.5% accuracy, respectively. CM outperformed the individual models, achieving an AUC of 0.99.

A novel automated recognition model was developed for accurate CLM detection in CE-IOUS by integrating image- and algorithm-based models.

In patients with colorectal cancer and unresectable liver-only metastases (CRLM), treatment with folinic acid, fluorouracil, and oxaliplatin (FOLFOX) plus irinotecan (FOLFOXIRI) and bevacizumab vs FOLFOX/folinic acid, fluorouracil, and irinotecan (FOLFIRI) plus bevacizumab increased progression-free survival, response, and R0/R1 resection/ablation rates, as well as toxic effects in RAS/BRAFV600E-variant and/or right-sided tumors. FOLFOX/FOLFIRI-panitumumab vs FOLFOX/FOLFIRI-bevacizumab increased response at the cost of more toxic effects in RAS/BRAFV600E wild-type, left-sided tumors.

To present long-term outcomes of treatment with FOLFOXIRI plus bevacizumab vs FOLFOX/FOLFIRI plus bevacizumab and FOLFOX/FOLFIRI plus panitumumab vs FOLFOX/FOLFIRI + bevacizumab.

The randomized phase 3 CAIRO5 trial included patients with initially unresectable CRLM in 46 Dutch centers and 1 Belgian center between November 2014 and January 2022. A liver expert panel repeatedly evaluated resectability.

Patients with RAS/BRAFV600E-variant and/or right-sided tumors randomly received FOLFOX/FOLFIRI-bevacizumab (group 1) or FOLFOXIRI-bevacizumab (group 2), and those with RAS/BRAFV600E wild-type, left-sided tumors received FOLFOX/FOLFIRI-bevacizumab (group 3) or FOLFOX/FOLFIRI-panitumumab (group 4). Adjuvant chemotherapy (ACT) after complete local treatment was recommended but not standard.

Overall survival (OS) was analyzed as a secondary outcome. Other outcomes were post hoc analyses.

A total of 530 patients (327 male [62%] and 203 female individuals [38%]; median age, 62 [IQR, 54-69] years) were randomized: 148 in group 1, 146 in group 2, 118 in group 3, and 118 in group 4. The median OS in group 1 was 23.6 (95% CI, 20.1-27.5) vs 24.1 (95% CI, 21.0-30.9) months in group 2 (hazard ratio [HR], 0.90; 95% CI, 0.70-1.17; P = .44), and 39.9 (95% CI, 30.7-44.6) in group 3 vs 38.3 (95% CI, 35.3-51.3) months in group 4 (HR, 0.95; 95% CI, 0.68-1.32; P = .75). OS was longest after complete local treatment without early (≤6 months) recurrence (64.3 months; 95% CI, 57.6 to not reached) and salvage local treatment options after early recurrence (58.9; 95% CI, 47.3 to not reached), followed by patients without salvage local treatment after early recurrence (30.5; 95% CI, 24.4-33.4) and with incomplete local treatment (28.7; 95% CI, 25.9-38.3), and worst in patients with continued unresectability (18.3; 95% CI, 15.7-20.0). After confounder adjustment, ACT was associated with longer OS (HR, 0.66; 95% CI, 0.44-0.98) and relapse-free survival (HR, 0.65; 95% CI, 0.48-0.88) and less early recurrence without salvage local treatment (odds ratio, 0.46; 95% CI, 0.25-0.85).

These results support using FOLFOX/FOLFIRI-bevacizumab for patients with initially unresectable CRLM irrespective of RAS/BRAFV600E status and tumor sidedness. Patients with complete local liver treatment with salvage local treatment in case of early recurrence had the longest OS. ACT might be considered for these patients.

ClinicalTrials.gov NCT02162563.

Chemotherapy can cause vascular and metabolic liver injury in patients with liver metastases, but scarce data are available. We aimed to (i) describe the prevalence of porto-sinusoidal vascular disorder (PSVD) among patients undergoing resection for liver metastases; and (ii) assess whether liver (LSM) and spleen stiffness measurements could diagnose PSVD and predict postoperative complications. This is a prospective single-center study enrolling consecutive patients undergoing hepatic resection for metastases at a tertiary center. For each patient, we evaluated previous exposure to chemotherapy, comorbidities, elastography, type of surgery, histological features at the resection specimen, morbidity (post-hepatectomy liver failure and major complications according to Clavien-Dindo), and 90-day survival. Sixty-eight patients were included, of whom 60 (88%) had received chemotherapy. Twenty-nine (44%) patients had PSVD. Spleen stiffness measurements <21 kPa (negative predictive value 87%) and >40 kPa (positive predictive value 100%) could accurately diagnose PSVD. PSVD significantly increased the risk of post-hepatectomy liver failure (22% vs. 45%) and major complications (11% vs. 31%). Preoperative LSM was associated with postoperative morbidity. The cutoff LSMs <4.5 and >8 kPa predicted the risk of clinically significant post-hepatectomy liver failure (0%, 11%, and 33% in LSM <4.5, 4.5-8, and >8 kPa, respectively) and major complications (0%, 25%, 44% in LSM <4.5, 4.5-8, and >8 kPa, respectively). PSVD is very common among patients undergoing liver surgery for metastases, and it is associated with increased morbidity. LSM and spleen stiffness measurements can correctly identify patients with PSVD and those at risk of clinically relevant postoperative complications.

Traditionally, colorectal liver metastases (CRLMs) are divided into "initially resectable" and "initially unresectable." The terminology "borderline resectable" continues to be elusive without any common consensus or definition. This narrative review aims to decode the conundrum of "borderline resectable CRLM (BR-CRLM)" and to discuss optimal treatment strategies.

A comprehensive review was performed using Medline/PubMed and Web of Science databases with a search period ending on January 1, 2024. Using PubMed, the terms "CRLM," "BR-CRLM," and "management of BR-CRLM" were searched.

The 2016 European Society for Medical Oncology guidelines defined the term "resectability" in CRLM using the "technical (surgical) criteria" and the "oncologically criteria." These 2 criteria form the basis of defining BR-CRLM. Thus, BR-CRLM can be either technically easy but with unfavorable oncologically criteria or technically difficult with favorable oncologically criteria. Although defining BR-CRLM by incorporating both these criteria seems to be the most logical way forward, there is currently a lot of heterogeneity in the literature. It is generally agreed upon that some form of chemotherapy needs to be administered in BR-CRLM before embarking on surgery. Conversion chemotherapy is used in patients with BR-CRLM in which there is a possibility of resection after effective downsizing. Along with improved effective chemotherapy, great strides have been made in pushing the limits of surgery to achieve resectability in this subset of patients.

Advanced surgical techniques and locoregional liver-directed therapies coupled with perioperative chemotherapy with or without targeted therapy have made long-term survival benefit, a reality in patients with BR-CRLM. Thus, the time has come to recognize "BR-CRLM" as a distinct entity.

To evaluate the response to neoadjuvant therapy in patients with colorectal liver metastases (CRLMs) using ultrasound(US) and contrast-enhanced ultrasound(CEUS), with correction to the tumor regression grade (TRG) of pathological results.

This study included patients with resectable CRLMs admitted from February to December 2022. After at least 4 cycles neoadjuvant therapy, all the patients received US and CEUS examinations within two weeks before hepatectomy. CEUS clips were postprocessed with color parameter imaging (CPI) and microflow imaging (MFI) analysis. Logistic regression analyses were used to develop an evaluation Nomogram. Ultrasound-based model was constructed to discriminate between the response (TRG1/2/3) and nonresponse (TRG4/5) groups at the lesion level. The model's predictive ability was evaluated using the C index and calibration curve, with decision curve analysis assessing the Nomogram's added value.

The study analyzed 105 CRLM lesions (the lesion with the highest diameter analyzed for each patient), with 43.8% showing a response to therapy. Univariate analysis identified calcification on US (p = 0.039), CEUS enhancement degree (p < 0.001), CEUS enhancement pattern (p<0.001), CEUS washout type (p < 0.001), CEUS necrosis (p < 0.001), CPI feeding artery (p = 0.003) and MFI pattern (p < 0.001) were significantly associated with TRG. The multivariate analysis showed CEUS enhancement pattern (p = 0.026), CEUS washout type (p = 0.018) and CEUS necrosis (p = 0.005) were independently associated with the neoadjuvant therapy response. A Nomogram with the three independent predictors was developed, with an AUC of 0.898.

The ultrasound-based model provided accurate evaluation of pathological tumor response to preoperative chemotherapy in patients with CRLM, and may help to decide the individualized treatment strategy.