Resection For Metastatic Colorectal Cancer Research Articles

Utility of Circulating Tumor DNA Assessment in Characterizing Recurrence Sites after Optimal Resection for Metastatic Colorectal Cancer.

Plasma circulating tumor DNA (ctDNA) is a promising biomarker for metastatic colorectal cancer (mCRC); however, its role in characterizing recurrence sites after mCRC resection remains poorly understood. This single-institution study investigated the timing of ctDNA detection and its levels in the context of recurrence at different sites after mCRC resection. Patients who underwent optimal resection of CRC metastases involving the peritoneum, distant lymph nodes, or liver, with serial postoperative tumor-informed ctDNA assessments (Signatera) were included. Recurrence sites, as defined by surveillance imaging or laparoscopy, were categorized as peritoneal-only and other distant sites (liver, lung, lymph nodes, or body wall). Among the 31 included patients, ctDNA was detected in all 26 (83.4%) patients with postoperative recurrence and was persistently undetectable in 5 patients who did not experience recurrence. At 3 months postsurgery, ctDNA was detected in 2 (25%) of 8 patients with peritoneal-only recurrence and 17 (94.4%) of 18 patients with distant recurrence (p < 0.001). Beyond 3 months, ctDNA was detected in the remaining 6 patients with peritoneal-only disease and 1 patient with distant disease. ctDNA detection preceded the clinical diagnosis of recurrence by a median of 9 weeks in both groups. At recurrence, peritoneal-only recurrent cases exhibited lower ctDNA levels (median 0.4 mean tumor molecules/mL, interquartile range 0.1 to 0.8) compared with distant recurrence (median 5.5 mean tumor molecules/mL, interquartile range 0.8 to 33.3, p = 0.004). Peritoneal-only recurrence was associated with delayed ctDNA detection and low levels of ctDNA after optimal resection for mCRC. ctDNA testing may effectively characterize recurrence sites and may help guide subsequent treatments specific to the disease sites involved.

Surveillance of resected metastatic colorectal cancer utilizing circulating DNA.

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

Minimally invasive versus open synchronous colorectal and hepatic resection for metastatic colorectal cancer: American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) analysis.

Minimally invasive versus open synchronous colorectal and hepatic resection for metastatic colorectal cancer: American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) analysis.

The efficacy and safety of anti-EGFR target agents in patients with potentially resectable metastatic colorectal cancer: a meta-analysis of randomized controlled trials

BackgroundAdding anti-epidermal growth factor receptor (anti-EGFR) target agents to conversion therapy may improve the resection rates and survival of patients with potentially resectable metastatic colorectal cancer (mCRC). This study aims to analyze the efficacy and safety of additional anti-EGFR target agents.MethodsA systematic search was conducted on PubMed, Web of Science, Embase, and Cochrane Library. And all relevant studies published in English before January 2023 were collected to explore the impact of additional anti-EGFR targeted agent on the efficacy and safety of patients with potentially resectable mCRC (PROSPERO: CRD42022340523, https://www.crd.york.ac.uk/PROSPERO/).ResultsThis study included a total of 8 articles, including 2618 patients. The overall response rate (ORR) and R0 resection rates of the experimental group were higher than those of the control group, while there was no significant difference in progression-free survival (PFS) and overall survival (OS) between the two groups. In RAS/KRAS wild-type patients, the ORR (RR: 1.20, 95% Cl: 1.02–1.41, p = 0.03), R0 resection rate (RR: 1.60, 95% Cl: 1.17–2.20, p = 0.003), PFS (HR: 0.80, 95% Cl: 0.68–0.93, p = 0.003), and OS (HR: 0.87, 95% Cl: 0.76–0.99, p = 0.031) of the experimental group were higher than those of the control group. While in KRAS mutant patients, there was no statistical difference between the two groups in ORR, R0 resection rate, PFS, and OS.ConclusionThe addition of anti-EGFR targeted agents can improve the prognosis of RAS/KRAS wild-type patients with potentially resectable mCRC, while KRAS mutant patients may not benefit. In addition, the overall safety factor was controllable.

ALBI and APRI score as prognostic factors for predicting the FABIB complications after liver resection in metastatic colorectal cancer.

e15577 Background: Previous studies and this study demonstrate that liver resection, even with subsequent extrahepatic relapse, may be associated with long-term survival, are very encouraging for future studies of the effectiveness of liver cytoreduction in conditions of minimal extrahepatic disease. These data also contribute to selective cytoreduction in extrahepatic sites. If it is necessary to achieve an oncological result (maximally extended liver resection), sometimes the surgical result suffers in the form of postoperative complications. The most serious complication of liver resection due to colorectal cancer metastases is postoperative liver failure, characterized by high levels of INR and bilirubin by day 5 after surgery. Methods: To classify the most frequent postoperative complications, the FABIB system has been developed, which includes Failure, Ascites, Bile leakage, Infection, Bleeding. We tried to evaluate the possibilities of using the ALBI and APRI indicators as one of the factors that must be taken into account when predicting the development of complications from the FABIB group. ALBI score is used in predicting the development of liver failure in patients with hepatocellular cancer. APRI score is a predictor of fibrosis and cirrhosis in patients suffering from hepatitis. Results: We have analyzed the results of liver resections in 174 patients with metastatic liver damage in colorectal cancer. Among them 57% are women, 43% are men. Metastatic lesion of the right lobe – 38 (21.8%), the left lobe – 78 (44.8%), right and left lobes – 58 (33.4%). Right–sided tumors - 25% - 43 patients, left–sided tumors - 75% - 131 patients. According to the FABIB classification, liver insufficiency was observed in 25 patients (14%), ascites in 4 patients (2.3%), bile leakage in 8 (4.6%), infectious complications in 9 (5%), bleeding in 15 patients (8%). A single-factor analysis of the variance of ALBI and APRI indicators on the day of surgery, the day after surgery and on the 5th day after surgery did not show a statistically significant difference in the groups with all FABIB complications and without FABIB complications. However, statistical analysis separately in each subgroup of complications revealed a statistically significant difference in ALBI and APRI in the groups with and without postoperative liver failure, as well as a statistically significant difference in the groups with and without bleeding. Conclusions: Thus, it can be concluded that ALBI score and APRI score can be used in the early postoperative period to predict the development of postoperative liver failure and hemorrhagic complications not only in patients with hepatocellular cancer or cirrhosis, but also in patients with colorectal cancer with liver metastases. It could be useful in patients who have undergone several lines of chemotherapy before liver resection or with a large tumor lesion of the liver.

Laparoscopic and Open Liver Resections for Colorectal Cancer Liver Metastasis in the Ukrainian State Center.

Background Minimally invasive liver resections for metastatic colorectal cancer have been increasingly performed all over the world with promising results. We planned the current studyto review our experience on this matter and compare short- and long-term outcomes of laparoscopicliver resection (LLR) and open liver resection(OLR) in patients with colorectal cancer liver metastasis (CRLM). Materials and methods This is a single-center retrospective analysis of patients with CRLM who underwent laparoscopic (n=86) and open (n=96) surgical treatment for metastatic liver lesions between March 2016 and November 2022. Tumor characteristics, intra- and postoperative results, overall survival (OS), and disease-free survival (DFS)were analyzed and compared. Results LLR was associated with significantly shorter surgery duration (180 minutes versus 295 minutes, p=0.03). There was no significant difference in blood loss between the two groups (100 mL versus 350 mL, p=0.061). Additionally, the laparoscopic approach was associated with significantly shorter hospital stays (6 days versus 9 days, p=0.004). The rate of major complications (Clavien-Dindo classification ≥ 3) was lower in the LLR group (5.8% versus 16.6%, p=0.037). There was no mortality in the LLR group, and in the OLR group, one lethal case was induced by mesenteric thrombosis on the fifth postoperative day. We did not find a statistically significant difference in the OS rate between the two groups at one, three, and five years: 97.3%, 74.7%, and 43.4%, respectively,in the OLR group and 95.1%, 70.3%, and 49.5%,respectively,in the LLR group (p=0.53). DFS at one, three, and five years were 88.7%, 52.3%, and 25.5%,respectively, in the LLR group and 71.9%, 53.1%, and 19.3%, respectively, in the OLR group(p=0.66). Conclusions This study showed that laparoscopic liver surgery is a safe and effective method of CRLM treatment in our center. LLR was associated with a decrease in major morbidity, shorter surgery duration, and reduced postoperative hospital stay. Minimally invasive liver resections showed similar oncological outcomes to the open approach in terms of overall and disease-free survival.

A Synchronous Robotic Resection of Colorectal Cancer and Liver Metastases-Our Initial Experience.

Synchronous robotic colorectal and liver resection for metastatic colorectal cancer (mCRC) is gaining popularity. This case series describes our initial institutional experience. A retrospective study of synchronous robotic colorectal and liver resections for metastatic colorectal cancer (March 2020 to December 2021). Eight patients underwent synchronous robotic resections. The median age was 59 (45-72), and the median body mass index was 29 (20-33). Seven received neoadjuvant chemotherapy, and five rectal cancers received neoadjuvant radiotherapy. One patient had a low anterior resection with major hepatectomy, two had low anterior resection with minor hepatectomy, and one had abdominoperineal resection with major hepatectomy. One patient had a left colectomy with minor hepatectomy, and two had right colectomies with minor hepatectomy. We used five robotic 8/12 mm ports in all cases. Extraction incisions were Pfannenstiel in four patients, colostomy site in two patients, one perineal incision, and one supra-umbilical incision. The median estimated blood loss was 200 mL (25-500), and the median operative time was 448 min (374-576). There were no intra-operative complications or conversions. Five patients had the liver resection first, and two of six anastomoses were performed before the liver resection. The Median length of stay was 4 days (3-14). There were two post-operative complications, prolonged ileus and DVT, with a Clavien-Dindo complication grade of I and II, respectively. There were no readmissions or reoperations. All colorectal and liver resection margins were negative. Synchronous robotic colorectal and liver resection can be performed effectively utilizing one port configuration with acceptable short-term outcomes and quality of oncologic resection.

Neutrophil-to-lymphocyte ratio and clinical outcomes in liver resection for metastatic colorectal cancer.

233 Background: The neutrophil-to-lymphocyte ratio (NLR) has been shown to correlate with overall and disease-free survival in patients with colorectal cancer. The data about prognostic value of the NLR in patients undergoing liver resection for colorectal liver metastases (CRLM) is limited. We aimed to describe the relationship between the NLR, overall survival and disease progression in patients who underwent liver resection for CRLM in a safety-net hospital. Methods: We identified patients who underwent liver resection with curative intent for metastatic colorectal cancer at a large safety net hospital between 2008 and 2020. All patients had a complete blood count with differential available within three months prior to resection. We compared patients who had a pre-operative NLR ≤3 with those who had a NLR &gt; 3, a cut-off based on ROC analysis. We used the Chi-squared statistic and t-test to compare the frequencies of categorical variables and the means of continuous variables, respectively. Multivariate survival analyses were performed using the Cox-regression model after adjusting for sex, age at liver resection, race/ethnicity, body mass index, insurance status, initial presentation of colorectal cancer (emergency room vs outpatient), primary malignancy (colon vs. rectal), temporality of CRLM (synchronous vs metachronous presentation with primary), staged vs simultaneous removal of primary mass and CRLM, number and size of liver CRLM, other metastatic sites at the time of liver resection, carcinoembryonic antigen (at initial diagnosis, before and after resection), and receipt of at least six months of peri-liver resection chemotherapy. Results: We identified 76 patients who underwent liver resection with curative intent for CRLM with a median follow up of 40.7 months. The population had a mean age of 56.2 (SD 9.9), was 50% female, and predominantly non-White (73.7%). Compared with patients who had a NLR ≤3 (N = 50), patients with a NLR &gt; 3 (N = 26) were more likely to be white (46.2% vs 16.0%) and have rectal cancer (61.5% vs 28.0%). In unadjusted analysis, patients with NLR &gt; 3 had 1.87 times (95% CI 1.01-3.47) increased risk of mortality, compared with patients who had an NLR ≤3. In adjusted analysis, patients with NLR &gt; 3 had 6.88 times (95% CI 1.61-29.42), increased risk of mortality, compared with patients who had an NLR ≤ 3. There was no significant difference in risk of CRLM recurrence or overall disease progression among patients with NLR ≤3 vs patients with NLR &gt; 3. Conclusions: An elevated pre-operative NLR &gt; 3 is a potential predictor of overall survival among patients undergoing liver resection for metastatic colorectal cancer. This widely available test may aid clinicians in pre-operative risk stratification.

HCRN GI16-288: A phase II trial of perioperative CV301 vaccination in combination with nivolumab and systemic chemotherapy for resectable hepatic-limited metastatic colorectal cancer—Preliminary efficacy and correlative results.

103 Background: Novel strategies to improve the efficacy of immune checkpoint inhibitors in microsatellite stable (MSS) mCRC are needed. CV301 is a vector-based vaccine that expresses carcinoembryonic antigen (CEA) and mucin 1 (MUC1), and in a phase II study in resected hepatic limited mCRC significantly improved OS compared with unvaccinated contemporary controls. Methods: In this multi-center randomized phase II study, patients with previously untreated resectable hepatic-limited mCRC were randomized to perioperative nivolumab + mFOLFOX +/- CV301 (Arm B) with a primary endpoint of 3-year OS. Treatment included mFOLFOX-nivo (+/- CV) x 4 cycles followed by resection, then 8 more cycles of mFOLFOX-nivo followed by maintenance nivo monthly for two years in both arms, and CV boosters concurrently with mFOLFOX, and then every 3 months for two years in arm B. Secondary endpoints of ORR (following induction pre-resection), PRR, and safety were determined. Correlative analyses included immune cell quantification using Immunoscore and T-cell clonality. Results: 17 patients were enrolled prior to premature closure for slow accrual (8 arm A, 9 arm B). At the time of data cutoff, 5 patients remained on treatment and no deaths had occurred. One patient was removed from study due to protocol non-compliance. The median age was 61, majority were male (59% vs 41%), and ECOG PS 0-1 (71% 0, 17% 1). All patients had complete surgical resection. Four patients (24%) experienced a SAE related to drug. The TRAE rate was 40.3%,. No AEs delayed/prevented surgical resection. The ORR in arm A was 50% (including 4 CR) and 87.5% in arm B (including 7 CR) (p=0.129, NS). There was no significant difference in pathologic response (p=0.9047). Correlative analyses demonstrated the Immunoscore CD3/CD8 predicted response to mFOLFOX + nivolumab, but did not correlate with response to CV301, though CV301 may induce a shift to predominantly cytotoxic CD8+ T cells. While there was no significant difference in T cell repertoire, clonality, fraction (TCFr) or richness, patients in arm B had significant decreases in blood TCFr and increase in tumor TCFr with treatment; those with CR had higher TCFr and clonality. Conclusions: The addition of CV301 to perioperative nivolumab and mFOLFOX was safe, did not delay or prevent surgical resection, and gave a higher response (p=ns due to sample size). Changes in T cells suggest a vaccine response. Clinical trial information: NCT03547999 . [Table: see text]

Outcomes Following Treatment with FOLFOX for Patients with Resectable or Potentially Resectable Metastatic Colorectal Cancer: A Population-based Cohort Study

AimsTo evaluate the safety and effectiveness of oxaliplatin-based combination chemotherapy for patients with metastatic colorectal cancer (mCRC) to extrahepatic sites. Materials and methodsWe conducted a population-based retrospective study examining the safety and effectiveness of perioperative oxaliplatin for resectable or potentially resectable colorectal metastases in Ontario, Canada. Outcomes were also compared with patients with liver-only metastases. Patients received oxaliplatin for mCRC between 1 January 2013 and 30 June 2020. ResultsIn total, 192 patients had extrahepatic metastases. Seventy per cent had R0 metastasectomy. The 3-year disease-free survival and overall survival were 62% and 79%, respectively; <4% of patients died within 60 days of metastasectomy and 74–90% of patients received treatment according to recommendations from a multidisciplinary setting. Compared with liver-only controls (n = 1306), patients had mCRC to the lung only (n = 115), lung and liver (n = 55) and liver with non-pulmonary site (n = 22). Extrahepatic metastases were more likely to be found for patients whose primary colorectal resection had positive margins (14% versus 7%, P = 0.005) and primary tumours located in the rectum [odds ratio 4.01 (2.31–6.97)]. After adjustment, there was no difference in overall survival between liver-only controls and patients with lung-only [hazard ratio 0.82 (0.59–1.15)] or liver and lung metastases [hazard ratio 1.26 (0.85–1.87)] (P = 0.24). In total, 79/115 (69%) of patients with lung-only metastases had a metastasectomy compared with 645/1306 (49%) and 15/55 (27%) of patients with liver-only and liver and lung metastases, respectively. Hospital visits were similar between patients with liver-only and extrahepatic metastases. ConclusionOxaliplatin-based chemotherapy for patients with resectable or potentially resectable mCRC with extrahepatic metastases was safe and resulted in similar outcomes in appropriately selected patients when compared with patients with liver-only metastases.

Y-90 can cause reliable tumor regression: Ready for prime time?

Background: Surgical resection of metastatic colorectal cancer (mCRC) within the liver results in an approximately 30% 5-year survival, however the majority of patients are unresectable at presentation. The aim of this study is to assess the use of Yittrium-90 (Y-90) as a bridge to future resection.

48P Long-term clinical outcomes after the second metastasectomy in patients (pts) with resected metastatic colorectal cancer (mCRC)

Primary tumor resection and metastasectomy are curative options in some pts with mCRC. However, there is still a paucity of data regarding clinical outcomes and risk factors after disease recurrence and second metastasectomy in these pts.

Recent Advance in the Surgical Treatment of Metastatic Colorectal Cancer-An English Version.

Stage IV colorectal cancer (CRC) has heterogeneous characteristics in tumor extent and biology. The overall survival of patients with metastatic CRC has improved with the development of multimodal treatments and new chemotherapeutic drugs. Resection of metastatic CRC is performed for liver, lung, or peritoneal metastases. Conversion surgeries to resect oligometastatic lesions have been developed with tumor regression using chemotherapeutic agents. Two-stage hepatectomy has extended the surgical indications for patients with metastatic CRC. Synchronous liver and primary tumor resection can be considered in patients with adequate conditions. Local ablation with radiotherapy can be used to treat lung metastasis. In the treatment of patients with CRC with peritoneal metastasis, cytoreductive surgery with hyperthermic intraperitoneal chemotherapy can be considered. Surgical treatments should be performed in patients with symptomatic primary tumors with unresectable metastasis. However, primary tumor resection in patients with asymptomatic CRC with synchronous, unresectable metastases did not show overall survival benefits in recent studies. Therefore, the treatment of metastatic CRC is challenging due to the variable tumor extent and heterogenous characteristics. Tailored surgical treatments and multidisciplinary approaches may improve survival and the quality of life in patients with metastatic CRC.

Surgical treatment for metastatic colorectal cancer

Background: Stage IV colorectal cancer (CRC) exhibits heterogeneous characteristics in tumor extent and biology. The overall survival of patients with metastatic CRC has improved with the development of multimodal treatments and new chemotherapeutic drugs.Current Concepts: Resection of metastatic CRC is performed for liver, lung, or peritoneal metastases. Conversion surgeries to resect oligometastatic lesions have been developed with tumor regression using chemotherapeutic agents. Two-stage hepatectomy has extended the surgical indications for patients with metastatic CRC. Synchronous liver and primary tumor resection can be considered in patients with adequate conditions. Local ablation with radiotherapy can be used to treat lung metastasis. Meanwhile, for treating patients with CRC with peritoneal metastasis, cytoreductive surgery with hyperthermic intraperitoneal chemotherapy can be considered. Surgical treatments should be performed in patients with symptomatic primary tumors with unresectable metastasis. However, in recent studies, primary tumor resection in patients with asymptomatic CRC with synchronous, unresectable metastases did not show overall survival benefits.Discussion and Conclusion: The treatment of metastatic CRC is challenging because of the variable tumor extent and heterogenous characteristics. Tailored surgical treatments and multidisciplinary approaches may improve the survival and quality of life of patients with metastatic CRC.

Efficacy and safety of triplet chemotherapy plus anti-EGFR agents in metastatic colorectal cancer: a systematic review and meta-analysis

BackgroundTo date, the optimal treatment for potentially resectable metastatic colorectal cancer (mCRC) patients has yet to be determined. Encouraging results have been reported in studies exploring the efficacy of triplet chemotherapy plus anti-epidermal growth factor receptor (anti-EGFR) target agents. Thus, we conducted a meta-analysis to evaluate the efficacy and safety of triplet chemotherapy plus anti-EGFR target agents.MethodsWe systematically searched the PubMed, Embase, and Web of Science databases from December 2004 to October 2021 for studies examining the efficacy of triplet chemotherapy plus anti-EGFR target agents in mCRC patients. The primary outcomes were the objective response rate (ORR) and R0 resection rate (R0RR), and the secondary outcomes were median progression-free survival (mPFS), median overall survival (mOS), and toxicity. Data were analyzed with R software 4.1.2.ResultsFourteen studies comprising 762 patients with mCRC were included in this meta-analysis. Analysis with a random effects model revealed that after treatment with triplet chemotherapy plus anti-EGFR target agents, the pooled ORR was 82% (95% CI= 76–88%, I2= 76%), and the pooled R0RR of colorectal liver metastasis (CLM) was 59% (95% CI= 49–68%, I2= 60%). The mPFS ranged from 9.5 to 17.8 months, and the mOS ranged from 24.7 to 62.5 months. A total of 648 grade 3 or 4 adverse events were reported; the most commonly reported events were diarrhea (174/648), neutropenia (157/648), and skin toxicity (95/648), which had pooled prevalence rates of 29% (95% CI= 20–39%, I2= 84%), 28% (95% CI= 20–37%, I2= 77%), and 17% (95% CI= 11–24%, I2= 66%), respectively.ConclusionsTriplet chemotherapy plus anti-EGFR agents therapy seems to be capable of increasing the ORR of mCRC patients and the R0RR of CLM patients. The toxicity of this treatment is manageable. High-quality randomized controlled trial (RCT) studies are required for further validation.

Optimal Surgical Indications for Resectable Metastatic Colorectal Cancer with BRAF V600E Mutation

Optimal Surgical Indications for Resectable Metastatic Colorectal Cancer with BRAF V600E Mutation

Current status, controversy and challenge in the neoadjuvant immunotherapy of colorectal cancer

Neoadjuvant therapy for colorectal cancer is widely used in rectal cancer, locally advanced colon cancer, and resectable metastatic and recurrent colorectal cancer. Mismatch repair deficient(dMMR) and microsatellite instablity-high (MSI-H) colorectal cancer patients who benefit from the efficacy of immune checkpoint inhibitors are expected to further improve the efficacy of traditional neoadjuvant therapy based on radiotherapy and chemotherapy. In this paper, the current status of immunotherapy (with emphasis on immune checkpoint inhibitors) is elucidated, and the opportunities of its application in neoadjuvant therapy are analyzed, including poor sensitivity of dMMR tumors to traditional therapy, good immune response of early tumors, predictable, manageable and controllable toxicity of immune checkpoint inhibitors. Colorectal cancer patients have growing and diverse needs to be met. Current controversies and challenges are analyzed, and the future directions are pointed out, including active screening of benefit groups, exploration of efficacy prediction markers, optimization of neoadjuvant immunotherapy models, attention to efficacy evaluation and new therapeutic endpoints. Neoadjuvant therapy should be effective, moderate and accurate based on the treatment target. It is the prerequisite and basis to guarantee medical safety and improve therapeutic effect to attach importance to the standardization and safety of clinical research and to pay attention to patients' interests and legal and ethical demands.

Immune microenvironment in patients with mismatch-repair-proficient oligometastatic colorectal cancer exposed to chemotherapy: the randomized MIROX GERCOR cohort study.

In the era of immune checkpoint inhibitors, understanding the metastatic microenvironment of proficient mismatch repair/microsatellite stable (pMMR/MSS) colorectal cancer (CRC) is of paramount importance to both prognostication and the development of more effective novel therapies. In this study, primary and paired metastasis tissue samples were collected from patients with resectable metastatic CRC treated with adjuvant FOLFOX or peri‐operative chemotherapy in the MIROX phase III prospective study. In total, 74 cancer tissues were stained for CD3, CD8, Forkhead box protein 3 (FOXP3), programmed cell death protein‐1 (PD‐1, invasive front, stromal, intra‐epithelial compartments), and programmed death‐ligand 1 (PD‐L1, tumor, immune cells). The immune profiling of primary CRC had a limited value to predict the immune context of paired metastases for all markers but CD3+. The expression of CD8 and PD‐L1 was higher in metastases after neoadjuvant FOLFOX. In metastases, both CD3 T cells at the invasive front and PD‐L1 expressions on immune cells were predictive of better disease‐free survival. These results show that the effect of FOLFOX on modifying the immune microenvironment in resected CRC metastases and measurement of PD‐L1 expression and tumor‐infiltrating CD8 T cells in pMMR/MSS metastatic tissue samples could improve treatment strategies of metastatic CRC patients.

Association of Preoperative Physical Activity with Short- and Long-Term Outcomes in Patients Undergoing Palliative Resection for Metastatic Colorectal Cancer: An Inverse Probability of Treatment Weighting Analysis.

Simple SummaryPhysical activity is linked to the risk and the prognosis of colorectal cancer. However, the impact of preoperative physical activity on postoperative short-term and long-term outcomes is limited. The aim of our study was to elucidate the relationship of preoperative physical activity and postoperative outcomes in metastatic colorectal cancer patients who underwent palliative resection. After the inverse probability of the treatment weighting process, the metabolic equivalent of task < 12 group had a higher postoperative morbidity rate and mortality rate. No significant difference was found in overall survival. In patients undergoing palliative resection for metastatic colorectal cancer, preoperative leisure-time physical activity with the metabolic equivalent of task ≥ 12 was associated with reduced short-term postoperative morbidity and mortality; however, no difference was detected in long-term survival.A lack of physical activity is a generally accepted risk factor for colorectal cancer. However, research on the effect of preoperative physical activity on postoperative and long-term outcomes is limited, especially in patients with stage IV colorectal cancer who underwent palliative surgery. Patients who underwent bowel resection for stage IV primary colorectal cancer between January 1995 and December 2016 were retrospectively enrolled. A total of 2185 patients were divided into two groups according to preoperative leisure-time weekly physical activity as assessed by metabolic equivalent of task (MET) values: MET < 12 (n = 1845) and MET ≥ 12 (n = 340). Inverse probability of treatment weighting (IPTW) was used to reduce imbalance and selection biases between the two groups. After the IPTW process, the MET < 12 group showed a higher postoperative morbidity rate (18.7% vs. 10.6%; p < 0.001) and mortality rate (2.4% vs. 0.6%; p < 0.001) than the MET ≥ 12 group. No significant difference was found in overall survival. Weekly preoperative leisure-time physical activity with MET ≥ 12 was associated with reduced short-term postoperative morbidity and mortality in patients undergoing palliative resection for metastatic colorectal cancer. However, no difference was detected in long-term survival.

Laparoscopic vs open liver resection for metastatic colorectal cancer: analysis of surgical margin status and survival.

Liver resection represents the curative treatment of choice for patients with colorectal liver metastases (CRLM). Laparoscopic hepatectomy in CRLM is considered a safe approach. However, the information on their oncological results in the different series is deficient. This study aimed to compare the surgical margin, overall survival (OS), and disease-free survival (DFS) in patients with oncological resections of CRLM according to the type of surgical approach performed. Between April 2007 and June 2017, 263 patients with CRLM underwent hepatic resection. Inclusion criteria were initial resectability, tumor size ≤ 50mm, 3 or less metastases, no bilobar involvement, and absence of extrahepatic disease. A propensity score was performed to adjust the indication bias. Eighty-two patients were included (56 open and 26 laparoscopic). Twenty-eight (50%) patients had synchronous presentation in the open approach and 6 (23%) in the laparoscopic approach (p = 0.021), with more frequent simultaneous open resections (p = 0.037). The resection margin was positive (R1) in 5 patients with an open approach and 2 with a laparoscopic approach (8.9% and 7.6% respectively; p = 0.852). Nine patients (16%) with conventional approach and 2 (7.7%) with laparoscopic approach had local complications (p = 0.3). There was one death in the open group and none in the laparoscopic. There were no significant differences in OS and DFS rate between both groups (1-3years, OS: 92-77% and 96-75% respectively; 1-3years, DFS: 63-20% and 73-36% respectively). There were no significant differences in terms of surgical margin, OS rate, and DFS rate between the laparoscopic and open approach in patients with CRLM.