Colorectal Liver Metastases Research Articles

The impact of Kirsten rat sarcoma (KRAS) status on local tumor progression after surgical ablation of colorectal liver metastases

BackgroundKirsten rat sarcoma mutation was reported to adversely affect local tumor control after percutaneous ablation of colorectal liver metastasis. Nevertheless, the effect of Kirsten rat sarcoma mutation on surgical ablation has not been investigated in the literature. The aim of this study is to analyze the impact of Kirsten rat sarcoma mutation on local recurrence after surgical ablation of colorectal liver metastasis. MethodsThis was an institutional review board–approved study of patients who underwent surgical ablation of colorectal liver metastasis between 2005 and 2023 at a single center and underwent Kirsten rat sarcoma testing with ≥1 year follow-up. Local recurrence was analyzed using univariate Kaplan–Meier and multivariate Cox hazard models. ResultsA total of 163 patients with 424 lesions fulfilled inclusion criteria. Fifty (30.7%) patients received radiofrequency ablation and 113 (69.3%) patients received microwave ablation. Fifty-seven patients (32.2%) with 177 lesions were found to have a Kirsten rat sarcoma mutation. Patients with Kirsten rat sarcoma mutation had a larger number of tumors, percentage of posteriorly located tumors, and tumor burden score compared with those with wild-type Kirsten rat sarcoma. Nevertheless, there was no difference between the groups regarding local recurrence per lesion (15% vs 17%, respectively, P = not significant). Independent predictors of local recurrence included tumor size, ablation margin, and blood vessel proximity for radiofrequency ablation compared with tumor size and ablation margin for microwave ablation. ConclusionThere was no effect of Kirsten rat sarcoma mutations on local recurrence after surgical radiofrequency ablation or microwave ablation of colorectal liver metastasis in this study. Tumor size and ablation margin remained as independent predictors.

539P Hepatic arterial infusion chemotherapy combined with sintilimab and regorafenib as adjuvant therapy for colorectal liver metastasis patients with high risk of recurrent: A single-arm, phase II study

539P Hepatic arterial infusion chemotherapy combined with sintilimab and regorafenib as adjuvant therapy for colorectal liver metastasis patients with high risk of recurrent: A single-arm, phase II study

589P Simultaneous resection versus staged resection for conversion surgery for initially unresectable colorectal liver metastasis: A prospective cohort study

589P Simultaneous resection versus staged resection for conversion surgery for initially unresectable colorectal liver metastasis: A prospective cohort study

549P Combined morphometric immune signatures define the prognosis of patients with resectable colorectal liver metastases

549P Combined morphometric immune signatures define the prognosis of patients with resectable colorectal liver metastases

Comment on "Surgical Margin of Resected Colorectal Liver Metastases: How Accurate Is Surgeon Prediction?"

Comment on "Surgical Margin of Resected Colorectal Liver Metastases: How Accurate Is Surgeon Prediction?"

PD-1 blockade combined with chemotherapy and bevacizumab in DNA mismatch repair-proficient/microsatellite stable colorectal liver metastases.

Single-agent immunotherapy is less effective in patients with DNA mismatch repair-proficient/microsatellite stable (pMMR/MSS) metastatic colorectal cancer (mCRC). Whether pMMR/MSS mCRC patients benefit from combination immunotherapy remains unclear. This study aimed to evaluate the efficacy and safety of anti-programmed cell death protein 1 (PD-1) therapy combined with chemotherapy and bevacizumab in pMMR/MSS colorectal liver metastases (CRLM) patients. A total of 12 patients with pMMR/MSS CRLM treated at The Sixth Affiliated Hospital of Sun Yat-sen University were enrolled. All patients were treated with at least 4 doses of PD-1 monoclonal antibody combined with chemotherapy and bevacizumab as neoadjuvant/adjuvant therapy. A total of 10 of the 12 patients received the combined therapies before primary tumor resection; the disease control rate (DCR) was 100% (10/10), and the objective response rate (ORR) was 70% (7/10). The ORR of liver metastases was 75% (9/12). Pathological complete response (pCR) was achieved in 1 primary tumor patient and 2 patients with hepatic lesions. A total of 5 patients underwent simultaneous resection of the primary tumor and liver metastases; 9 patients underwent microwave ablation for liver metastases. A total of 7 patients were assessed as having no evidence of disease (NED) with a median progression-free survival (PFS) interval of 9.2 (1.5-15.8) months after multimodality treatments for both primary and metastatic lesions. No severe immune-related adverse events (irAEs) and operational complications were observed. PD-1 blockade combined with chemotherapy and bevacizumab might be safe and effective for patients with pMMR/MSS CRLM. This treatment strategy might lead to better tumor regression and a higher chance of achieving NED.

Identification of A0 minimum ablative margins for colorectal liver metastases: multicentre, retrospective study using deformable CT registration and artificial intelligence-based autosegmentation.

Several ablation confirmation software methods for minimum ablative margin assessment have recently been developed to improve local outcomes for patients undergoing thermal ablation of colorectal liver metastases. Previous assessments were limited to single institutions mostly at the place of development. The aim of this study was to validate the previously identified 5 mm minimum ablative margin (A0) using autosegmentation and biomechanical deformable image registration in a multi-institutional setting. This was a multicentre, retrospective study including patients with colorectal liver metastases undergoing CT- or ultrasound-guided microwave or radiofrequency ablation during 2009-2022, reporting 3-year local disease progression (residual unablated tumour or local tumour progression) rates by minimum ablative margin across all institutions and identifying an intraprocedural contrast-enhanced CT-based minimum ablative margin associated with a 3-year local disease progression rate of less than 1%. A total of 400 ablated colorectal liver metastases (median diameter of 1.5 cm) in 243 patients (145 men; median age of 62 [interquartile range 54-70] years) were evaluated, with a median follow-up of 26 (interquartile range 17-40) months. A total of 119 (48.9%) patients with 186 (46.5%) colorectal liver metastases were from international institutions B, C, and D that were not involved in the software development. Three-year local disease progression rates for 0 mm, >0 and <5 mm, and 5 mm or larger minimum ablative margins were 79%, 15%, and 0% respectively for institution A (where the software was developed) and 34%, 19%, and 2% respectively for institutions B, C, and D combined. Local disease progression risk decreased to less than 1% with an intraprocedurally confirmed minimum ablative margin greater than 4.6 mm. A minimum ablative margin of 5 mm or larger demonstrates optimal local oncological outcomes. It is proposed that an intraprocedural minimum ablative margin of 5 mm or larger, confirmed using biomechanical deformable image registration, serves as the A0 for colorectal liver metastasis thermal ablation.

Robotic surgery for colorectal liver metastases (CRLM): A systematic literature review with meta-analysis.

Colorectal Cancer (CRC) is the third most prevalent cancer (10.2%) with the second highest mortality (9.2%).[1] Up to 14.5% of patients present with synchronous metastases and 12.8% will develop metachronous metastases within 5 years. The treatment for these metastases is resection. [2] In this study we perform a systematic search of the literature about robotic versus laparoscopic liver resections of colorectal liver metastases (CLRM). We include 16 studies. We describe the patient and tumor characteristics. We also describe operation characteristics (rate of major resections, operation time, usage and duration of Pringle, conversion rate, complication rate, R0 margin rate, estimated blood loss, length of stay, mortality and recurrence. Using this data we perform a meta-analysis: no significant difference in operation time was found between robotic and laparoscopic liver resections. There was significantly lower conversion rate, significantly higher R0 margin rate, significantly lower blood loss in the robotic group. We conclude that robotic surgery is promising in the therapy of CRLM. In the future there is need for RCT to compare robotic versus laparoscopic liver surgery for CRLM. Furthermore a longer follow-up is needed.

Cytoreductive Surgery With Hyperthermic Intraperitoneal Chemotherapy and Liver Resection is a Treatment Option for Patients With Peritoneal and Liver Metastases From Colorectal Cancer.

Colorectal cancer frequently metastasize to the liver and peritoneum, and is associated with a poor prognosis. In selected patients, a benefit in overall survival (OS) was shown for both peritoneal metastases (PM-CRC) offered cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC), and colorectal liver metastases (CLM) treated with surgical resection. However, the presence of CLM was considered a relative contraindication to CRS-HIPEC, causing a paucity in outcome data in this patient group. Patient with PM-CRC having CRS-HIPEC at a single national center between 2007 and 2023, with additional intervention for CLM, were included (previous curative treatment for extra-peritoneal and extra-hepatic metastases was allowed). Three groups were defined: CLM before CRS-HIPEC (preCRS-HIPEC); CLM resected simultaneously with CRS-HIPEC (simCRS-HIPEC); CLM after CRS-HIPEC (postCRS-HIPEC), aiming to retrospectively analyze outcomes. Fifty-seven patients were included and classified as: preCRS-HIPEC (n=11), simCRS-HIPEC (n=29), and postCRS-HIPEC (n=17). Median peritoneal cancer index (PCI) was 8, 13 patients had severe complications (Clavien-Dindo ≥3), and no 90-day mortality. Median OS was 48 months after CRS-HIPEC. PCI was a predictor of OS (HR 1.11, P<0.001). We observed no difference in short or long-term outcomes between intervention groups. This study demonstrate that patients with CLM having CRS-HIPEC had comparable OS to reports on CRS-HIPEC only, likely explained by a low PCI. Simultaneous CLM resection did not increase the risk of severe complications. In this national cohort, CRS-HIPEC and CLM intervention offers long-term survival, suggesting that this treatment may be offered to selected patients with PM-CRC and CLM.

The association between histopathological growth patterns with tumor budding and poorly differentiated clusters in colorectal liver metastasis treated with preoperative systemic therapy.

The liver's unique cellular structure makes it a frequent site for metastatic cancer. In colorectal liver metastasis (CRLM), surgical resection is essential for long-term survival. Histopathological growth patterns (HGPs) in CRLM, including desmoplastic and nondesmoplastic patterns, provide critical prognostic information. Tumor budding (TB) and poorly differentiated clusters (PDCs), indicators of aggressive cancer behavior, are evaluated using standardized histological scoring systems and are linked to epithelial-mesenchymal transition. This study explored the correlation between HGPs, TB, and PDCs in CRLM. Archived data from Thammasat University Hospital, including resected CRLM specimens, were analyzed. This study evaluated 51 CRLM resection specimens treated with preoperative systemic therapy, finding most to be nondesmoplastic with low TB and grade 1 PDC. Desmoplastic growth was significantly more prevalent in cases receiving preoperative chemotherapy than those that did not. Higher 3-year mortality was noted in nondesmoplastic groups and those with higher TB and tumor regression grade (TRG) scores. Significant correlations were observed between HGPs, TB, and PDCs, despite challenges in assessing these parameters due to issues with noncancer cells, extracellular mucin, bile ductular proliferation, and retraction artifacts. This study underscores the prognostic significance of HGPs, TB, PDCs, and TRG scores in CRLM, highlighting the need for precise histopathological evaluation for more accurate prognostic implications.

Impact of Infrared Indocyanine Green Fluorescence imaging-guided Laparoscopic Hepatectomy on Securing the Resection Margin for Colorectal Liver Metastasis.

Laparoscopic hepatectomy for colorectal liver metastases (CRLM) is performed worldwide. However, owing to a lack of palpatory information and difficulties associated with accurate intraoperative ultrasonographic diagnosis, the tumor may be exposed at the hepatic transection margin. This study aimed to investigate the pathological significance of near-infrared (NIR) fluorescence imaging with indocyanine green (ICG)-guided laparoscopic hepatectomy and determine its usefulness in securing the resection margin for CRLMs. Fifty-nine patients who underwent laparoscopic hepatectomy for CRLM using NIR fluorescence imaging between February 2017 and June 2021 at Sapporo Medical University Hospital were included. Generally, all patients received intravenous ICG (2.5mg/body) as a fluorescence agent 1 to 2 days before surgery. During the surgical procedure, real-time NIR fluorescence imaging was repeatedly performed to assess the surgical margins. Of the 94 tumors in 59 patients, laparoscopic NIR fluorescence imaging identified 56 tumors (59.6%) on the liver surface. Pathological analysis indicated clear margins in 96.6% (57/59) of patients. Examination of paraffin-embedded sections, which were successful in only 20 of 94 cases (21.3%), revealed that there were no tumor cells positive for NIR fluorescence, and the median distance of the continuous fluorescent signal from the tumor margin was 1.074mm. We demonstrated a high R0 rate using NIR fluorescence-guided hepatectomy. This technique has the potential to improve intraoperative tumor identification and tumor margin assurance and reduce the rate of positive resection margins in patients with CRLMs.

Prognostic implications of margin status in association with systemic treatment in a cohort study of patients with resection of colorectal liver metastases.

This study investigates the impact of margin status after colorectal liver metastasis (CLM) resection on outcomes of patients after neoadjuvant treatment versus those who underwent upfront resection. An international collaborative database of CLM patients who underwent surgical resection was used. Proportional hazard regression models were created for single and multivariable models to assess the relationship between independent measures and median overall survival (mOS). R1 was associated with worse OS in the neoadjuvant group (mOS: 51.8 m for R0 vs. 26.0 m for R1; HR: 2.18). In the patients who underwent upfront surgery, R1 was not associated with OS. (mOS: 46.7 m for R0 vs. 42.6 m for R1). When patients with R1 in each group were stratified by adjuvant treatment, there was no significant difference in the neoadjuvant group, while in the upfront surgery group with R1, adjuvant treatment was associated with significant improvement in OS (mOS: 42.6 m for adjuvant vs. 25.0 m for no adjuvant treatment; HR: 0.21). R1 is associated with worse outcomes in the patients who receive neoadjuvant treatment with no significant improvement with the addition of adjuvant therapy, likely representing an aggressive tumor biology. R1 did not impact OS in patients with upfront surgery who received postoperative chemotherapy.

Locoregional therapy for colorectal liver metastases awaiting transplantation: Balancing tumor control with liver toxicity.

Locoregional therapy for colorectal liver metastases awaiting transplantation: Balancing tumor control with liver toxicity.

Patterns and Predictors of Recurrence After Curative Resection of Colorectal Liver Metastasis (CRLM).

Our study aims to determine the predictors and patterns of relapses after curative colorectal liver metastasis (CRLM) resection. A single-centre, retrospective study of CRLM patients operated between 2010 and 2022 was performed. The site of first recurrence was either hepatic (marginal (≤ 1cm) or extramarginal), extrahepatic, or both. Factors that predicted relapse patterns and overall survival were determined by multivariable Cox regression analysis with backward elimination of variables. The study consisted of 258 patients, with a similar proportion of synchronous (144; 56%) and metachronous(114; 43%) metastasis. At a 43-month median follow-up, 156 patients (60.4%) developed recurrences with 33 (21.1%) in the liver, 62(24.03%) extra-hepatic recurrences, and 58 (22.48%) having both. Isolated marginal liver relapses were seen in seven (9.89%) liver recurrence patients. The median overall and relapse-free survivals were 38months (30-54) and 13months (11-16), respectively. The 3-year liver-relapse-free survival was 54.4% (44.9-60.6). Size of liver metastases > 5cm (HR 2.06 (1.34-3.17), involved surgical margins (HR 2.16 (1.27-3.68)), and adjuvant chemotherapy (HR 1.89 (1.07-3.35)) were predictors of hepatic recurrences. Node positivity of primary (HR 1.61 (1.02-2.56)), presence of baseline extra-hepatic metastases (HR 0.30 (0.18-0.51)), size of liver metastases > 5cm (HR 2.02 (1.37-2.99)), poorly differentiated histology (HR 2.25 (1.28-3.49)), presence of LVI (HR 2.25 (1.28-3.94)), and adjuvant chemotherapy (HR 2.15 (1.28-3.61)) were predictors of extra-hepatic recurrences. The study found majority relapses occurred at extrahepatic sites whilst isolated marginal recurrences were few. The consistent predictors of recurrence were size and inability to deliver adjuvant therapy. A tailored adjuvant therapy might improve outcomes after liver metastasectomy in colorectal cancers.

Hepatic Resection as the Primary Treatment Method for Hepatocellular Carcinoma After Orthotopic Liver Transplantation.

Liver transplantation (LT) is the treatment of choice for end-stage liver disease and certain malignancies such as hepatocellular carcinoma (HCC). Data on the surgical management of de novo or recurrent tumors that develop in the transplanted allograft are limited. This study aimed to investigate the perioperative and long-term outcomes for patients undergoing hepatic resection for de novo or recurrent tumors after liver transplantation. The study enrolled adult and pediatric patients from 12 centers across North America who underwent hepatic resection for the treatment of a solid tumor after LT. Perioperative outcomes were assessed as well as recurrence free survival (RFS) and overall survival (OS) for those undergoing resection for HCC. Between 2003 and 2023, 54 patients underwent hepatic resection of solid tumors after LT. For 50 patients (92.6 %), resection of malignant lesions was performed. The most common lesion was HCC (n = 35, 64.8 %), followed by cholangiocarcinoma (n = 6, 11.1 %) and colorectal liver metastases (n = 6, 11.1 %). The majority of the 35 patients underwent resection of HCC did not receive any preoperative therapy (82.9 %) or adjuvant therapy (71.4 %), with resection their only treatment method for HCC. During a median follow-up period of 50.7 months, the median RFS was 21.5 months, and the median OS was 49.6 months. Hepatic resection following OLT is safe and associated with morbidity and mortality rates that are comparable to those reported for patients undergoing resection in native livers. Hepatic resection as the primary and often only treatment modality for HCC following LT is associated with acceptable RFS and OS and should be considered in well selected patients.

Efficacy and safety of hepatic arterial infusion chemotherapy combined with fruquintinib and tislelizumab for patients with microsatellite stable colorectal cancer liver metastasis following failure of multiple-line therapy.

The prognosis of microsatellite stable (MSS)-colorectal cancer liver metastasis (CRCLM) following failure of multi-line therapy remains dismal. The aim of this study is to evaluate the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) plus fruquintinib and tislelizumab (HAIC-F-T treatment) for MSS-CRCLM which failed from multiple-line therapy. From February 2021 to June 2023, 45 patients with MSS-CRCLM after failure of multiple-line therapy who received HAIC combined with fruquintinib and tislelizumab (HAIC-F-T triple treatment) were enrolled. The combination therapy included HAIC regimens with oxaliplatin and 5-fluorouracil or irinotecan, oxaliplatin, and 5-fluorouracil on days 1-2, intravenous tislelizumab (200 mg) before HAIC on day 1, and oral fruquintinb (3 mg/d) on day 3-21, every 4 weeks. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method. The follow-up ended on June 22, 2024, with a median follow-up time of 17.5 months. The objective response rate was 42.2%, and the disease control rate was 82.2%. The median OS was 15.3 months (95% confidence interval [CI]:12.634-17.966), and the median PFS was 7.5 months (95% CI:5.318-9.682). The independent risk factors related to worse OS were previous PD-1 immunotherapy (P = 0.021) and the number of HAIC-F-T triple treatment cycles of ≤ 2 (P = 0.007). The incidence of grade 3 or higher adverse events (AEs) was 20%, with the most frequent grade 3 or higher AEs being abdominal pain (3/45, 6.7%). HAIC combined with fruquintinib and tislelizumab may be an alternative salvage treatment for patients with MSS-CRCLM following failure of multiple-line therapy.

Targeting circ-0034880-enriched tumor extracellular vesicles to impede SPP1highCD206+ pro-tumor macrophages mediated pre-metastatic niche formation in colorectal cancer liver metastasis

BackgroundInformation transmission between primary tumor cells and immunocytes or stromal cells in distal organs is a critical factor in the formation of pre-metastatic niche (PMN). Understanding this mechanism is essential for developing effective therapeutic strategy against tumor metastasis. Our study aims to prove the hypothesis that circ-0034880-enriched tumor-derived extracellular vesicles (TEVs) mediate the formation of PMN and colorectal cancer liver metastasis (CRLM), and targeting circ-0034880-enriched TEVs might be an effective therapeutic strategy against PMN formation and CRLM.MethodsWe utilized qPCR and FISH to measure circRNAs expression levels in human CRC plasma, primary CRC tissues, and liver metastatic tissues. Additionally, we employed immunofluorescence, RNA sequencing, and in vivo experiments to assess the effect mechanism of circ-0034880-enriched TEVs on PMN formation and CRC metastasis. DARTS, CETSA and computational docking modeling were applied to explore the pharmacological effects of Ginsenoside Rb1 in impeding PMN formation.ResultsWe found that circ-0034880 was highly enriched in plasma extracellular vesicles (EVs) derived from CRC patients and closely associated with CRLM. Functionally, circ-0034880-enriched TEVs entered the liver tissues and were absorbed by macrophages in the liver through bloodstream. Mechanically, TEVs-released circ-0034880 enhanced the activation of SPP1highCD206+ pro-tumor macrophages, reshaping the metastasis-supportive host stromal microenvironment and promoting overt metastasis. Importantly, our mechanistic findings led us to discover that the natural product Ginsenoside Rb1 impeded the activation of SPP1highCD206+ pro-tumor macrophages by reducing circ-0034880 biogenesis, thereby suppressing PMN formation and inhibiting CRLM.ConclusionsCirc-0034880-enriched TEVs facilitate strong interaction between primary tumor cells and SPP1highCD206+ pro-tumor macrophages, promoting PMN formation and CRLM. These findings suggest the potential of using Ginsenoside Rb1 as an alternative therapeutic agent to reshape PMN formation and prevent CRLM.

Tranexamic Acid in Patients Undergoing Liver Resection

Tranexamic acid reduces bleeding and blood transfusion in many types of surgery, but its effect in patients undergoing liver resection for a cancer-related indication remains unclear. To determine whether tranexamic acid reduces red blood cell transfusion within 7 days of liver resection. Multicenter randomized clinical trial of tranexamic acid vs placebo conducted from December 1, 2014, to November 8, 2022, at 10 hepatopancreaticobiliary sites in Canada and 1 site in the United States, with 90-day follow-up. Participants, clinicians, and data collectors were blinded to allocation. A volunteer sample of 1384 patients undergoing liver resection for a cancer-related indication met eligibility criteria and consented to randomization. Tranexamic acid (1-g bolus followed by 1-g infusion over 8 hours; n = 619) or matching placebo (n = 626) beginning at induction of anesthesia. The primary outcome was receipt of red blood cell transfusion within 7 days of surgery. The primary analysis included 1245 participants (mean age, 63.2 years; 39.8% female; 56.1% with a diagnosis of colorectal liver metastases). Perioperative characteristics were similar between groups. Red blood cell transfusion occurred in 16.3% of participants (n = 101) in the tranexamic acid group and 14.5% (n = 91) in the placebo group (odds ratio, 1.15 [95% CI, 0.84-1.56]; P = .38; absolute difference, 2% [95% CI, -2% to 6%]). Measured intraoperative blood loss (tranexamic acid, 817.3 mL; placebo, 836.7 mL; P = .75) and total estimated blood loss over 7 days (tranexamic acid, 1504.0 mL; placebo, 1551.2 mL; P = .38) were similar between groups. Participants receiving tranexamic acid experienced significantly more complications compared with placebo (odds ratio, 1.28 [95% CI, 1.02-1.60]; P = .03), with no significant difference in venous thromboembolism (odds ratio, 1.68 [95% CI, 0.95-3.07]; P = .08). Among patients undergoing liver resection for a cancer-related indication, tranexamic acid did not reduce bleeding or blood transfusion but increased perioperative complications. ClinicalTrials.gov Identifier: NCT02261415.

A CT-based radiomics tumor quality and quantity model to predict early recurrence after radical surgery for colorectal liver metastases.

This study aimed to develop a tumor radiomics quality and quantity model (RQQM) based on preoperative enhanced CT to predict early recurrence after radical surgery for colorectal liver metastases (CRLM). A retrospective analysis was conducted on 282 cases from 3 centers. Clinical risk factors were examined using univariate and multivariate logistic regression (LR) to construct the clinical model. Radiomics features were extracted using the least absolute shrinkage and selection operator (LASSO) for dimensionality reduction. The LR learning algorithm was employed to construct the radiomics model, RQQM (radiomics-TBS), combined model (radiomics-clinical), clinical risk score (CRS) model and tumor burden score (TBS) model. Inter-model comparisons were made using area under the curve (AUC), decision curve analysis (DCA) and calibration curve. Log-rank tests assessed differences in disease-free survival (DFS) and overall survival (OS). Clinical features screening identified CRS, KRAS/NRAS/BRAF and liver lobe distribution as risk factors. Radiomics model, RQQM, combined model demonstrated higher AUC values compared to CRS and TBS model in training, internal and external validation cohorts (Delong-test P < 0.05). RQQM outperformed the radiomics model, but was slightly inferior to the combined model. Survival curves revealed statistically significant differences in 1-year DFS and 3-year OS for the RQQM (P < 0.001). RQQM integrates both "quality" (radiomics) and "quantity" (TBS). The radiomics model is superior to the TBS model and has a greater impact on patient prognosis. In the absence of clinical data, RQQM, relying solely on imaging data, shows an advantage in predicting early recurrence after radical surgery for CRLM.

Viscoelastic properties of colorectal liver metastases reflect tumour cell viability

BackgroundColorectal cancer is the third most common tumour entity in the world and up to 50% of the patients develop liver metastases (CRLM) within five years. To improve and personalize therapeutic strategies, new diagnostic tools are urgently needed. For instance, biomechanical tumour properties measured by magnetic resonance elastography (MRE) could be implemented as such a diagnostic tool. We postulate that ex vivo MRE combined with histological and radiological evaluation of CRLM could provide biomechanics-based diagnostic markers for cell viability in tumours.Methods34 CRLM specimens from patients who had undergone hepatic resection were studied using ex vivo MRE in a frequency range from 500 Hz to 5300 Hz with increments of 400 Hz. Single frequency evaluation of shear wave speed and wave penetration rate as proxies for stiffness and viscosity was performed, along with rheological model fitting based on the spring-pot model and powerlaw exponent α, ranging between 0 (complete solid behaviour) and 1 (complete fluid behaviour). For histological analysis, samples were stained with H&E and categorized according to the degree of regression. Quantitative histologic analysis was performed to analyse nucleus size, aspect ratio, and density. Radiological response was assessed according to RECIST-criteria.ResultsFive samples showed major response to chemotherapy, six samples partial response and 23 samples no response. For higher frequencies (> 2100 Hz), shear wave speed correlated significantly with the degree of regression (p ≤ 0.05) indicating stiffer properties with less viable tumour cells. Correspondingly, rheological analysis of α revealed more elastic-solid tissue properties at low cell viability and major response (α = 0.43 IQR 0.36, 0.47) than at higher cell viability and no response (α = 0.51 IQR 0.48, 0.55; p = 0.03). Quantitative histological analysis showed a decreased nuclear area and density as well as a higher nuclear aspect ratio in patients with major response to treatment compared to patients with no response (all p < 0.05).DiscussionOur results suggest that MRE could be useful in the characterization of biomechanical property changes associated with cell viability in CRLM. In the future, MRE could be applied in clinical diagnosis to support individually tailored therapy plans for patients with CRLM.