Chemotherapy For Colorectal Liver Metastases Research Articles

Predicting response to neoadjuvant chemotherapy for colorectal liver metastasis using deep learning on prechemotherapy cross-sectional imaging.

Deep learning models (DLMs) are applied across domains of health sciences to generate meaningful predictions. DLMs make use of neural networks to generate predictions from discrete data inputs. This study employs DLM on prechemotherapy cross-sectional imaging to predict patients' response to neoadjuvant chemotherapy. Adult patients with colorectal liver metastasis who underwent surgery after neoadjuvant chemotherapy were included. A DLM was trained on computed tomography images using attention-based multiple-instance learning. A logistic regression model incorporating clinical parameters of the Fong clinical risk score was used for comparison. Both model performances were benchmarked against the Response Evaluation Criteria in Solid Tumors criteria. A receiver operating curve was created and resulting area under the curve (AUC) was determined. Ninety-five patients were included, with 33,619 images available for study inclusion. Ninety-five percent of patients underwent 5-fluorouracil-based chemotherapy with oxaliplatin and/or irinotecan. Sixty percent of the patients were categorized as chemotherapy responders (30% reduction in tumor diameter). The DLM had an AUC of 0.77. The AUC for the clinical model was 0.41. Image-based DLM for prediction of response to neoadjuvant chemotherapy in patients with colorectal cancer liver metastases was superior to a clinical-based model. These results demonstrate potential to identify nonresponders to chemotherapy and guide select patients toward earlier curative resection.

Recurrence-risk stratification using the Beppu score and selection of perioperative chemotherapy for colorectal liver metastases.

The annual postoperative disease-free survival for colorectal liver metastases can be easily estimated by weighting six preoperative clinical parameters (Beppu score). We identified three recurrence-risk stratification groups: the low (≤6 points), moderate (7-10 points), and high-risk (≥11 points). For low-, moderate-, and high-risk patients, hepatectomy alone, hepatectomy with adjuvant chemotherapy, and hepatectomy with preoperative chemotherapy are recommended, respectively. The Beppu score enables the decision on the necessity and timing of perioperative chemotherapy.

Change in liver function and fat during pre-operative chemotherapy for colorectal liver metastases: results from the CLiFF study

Change in liver function and fat during pre-operative chemotherapy for colorectal liver metastases: results from the CLiFF study

Feasibility of Hepatic Artery Infusion Chemotherapy for Colorectal Liver Metastasis in an Indian Setting.

Hepatic artery infusion chemotherapy (HAIC) is a popular treatment modality for the treatment of colorectal liver metastasis (CRLM). The aim of this study was to determine the feasibility of HAIC for high-risk resected CRLM delivered using repeated femoral puncture and delivering 5-fluorouracil infusional chemotherapy along with systemic adjuvant chemotherapy. The present study is a retrospective review of a prospectively maintained database. All patients who underwent HAIC for colorectal liver metastases between July 2022 and July 2023 were included. A total of 12 patients were included in the study of which 11 completed four sessions as planned. The median age was 47 (29-73) years with nine male (81%) and two female (18%) patients. Rectum (n = 7, 63%) was the most common primary location. All patients received systemic chemotherapy with 5-fluorouracil-based regimens prior to HAIC (median 12 cycles). The median number of metastasis was 2 (1-8). Eight patients had metastasis in unilobar distribution (73%). On completion of HAIC treatment, nine patients (64%) were completely disease free with a median follow-up of 8 months. None of the patients experienced any immediate adverse events during or after completion of the procedure. Conventional HAIC comes with various challenges such as unavailability of the agent floxuridine and the specialized HAIC pump. Percutaneous HAIC has a lower chance of infection. The delivery of HAIC using repeated femoral punctures and 5FU chemotherapy was successful in over 90% of the patients making it a feasible option in the treatment of CRLM.

Hepatic Artery Infusion Pump Chemotherapy for Colorectal Liver Metastases: What Does the Colorectal Surgeon Need to Know?

Hepatic Artery Infusion Pump Chemotherapy for Colorectal Liver Metastases: What Does the Colorectal Surgeon Need to Know?

Expert Commentary on Hepatic Artery Infusion Pump Chemotherapy for Colorectal Liver Metastases.

Expert Commentary on Hepatic Artery Infusion Pump Chemotherapy for Colorectal Liver Metastases.

Autotaxin is a novel surrogate marker for oxaliplatin-related sinusoidal obstruction syndrome in patients with colorectal liver metastasis.

Chemotherapy for colorectal liver metastasis has improved dramatically over the past few decades. However, sinusoidal obstruction syndrome induced by oxaliplatin leads to increased severe morbidity after hepatectomy for colorectal liver metastasis. Autotaxin is a novel liver fibrosis marker known to be taken up and metabolized by sinusoidal endothelial cells. This study aimed to evaluate whether Autotaxin levels could be a novel surrogate marker of sinusoidal obstruction syndrome for colorectal liver metastasis. We retrospectively evaluated 73 consecutive patients who underwent hepatectomy for colorectal liver metastasis. We assessed the relationship between their preoperative Autotaxin levels and sinusoidal obstruction syndrome. Median Autotaxin level was 0.750 mg/L. Preoperative oxaliplatin-based chemotherapy for colorectal liver metastasis was administered to 51 patients, and sinusoidal obstruction syndrome was histologically observed in 45 patients. Patients who received the oxaliplatin based chemotherapy had significantly higher Autotaxin levels than those who did not (P = 0.038). Furthermore, Autotaxin levels were higher in patients with sinusoidal obstruction syndrome than in those without (P = 0.011). Univariate and multivariate analyses revealed that Autotaxin level can be an independent predictive factor for sinusoidal obstruction syndrome preoperatively (P = 0.001). Autotaxin level is a non-invasive and promising surrogate marker for predicting sinusoidal obstruction syndrome before surgical resection for colorectal liver metastasis. This article is protected by copyright. All rights reserved.

P-237 Percentage of residual fibrosis versus Rubbia-Brandt classification as predictors of overall survival in metastatic colorectal cancer. Which is better?

Pathologic response to preoperative chemotherapy for colorectal liver metastases (CRLM) has been associated with survival after hepatectomy in some publications. Rubbia-Brandt L et al stablished a five pathological categories classification with prognostic value in this setting. Poultsides GA et al, in 2012, published that fibrosis is the predominant chemotherapy-related pathologic alteration driving prognostic information. There are no publications comparing both pathologic prognostic classifications in a Cox regression model including other clinical variables that influence prognosis.

Upfront surgery or neoadjuvant chemotherapy for colorectal liver metastases? A machine-learning decision-tree to identify the best potential policy

Simone FAMULARO*, Flavio MILANA, Matteo CIMINO, Eloisa FRANCHI, Guido COSTA, Fabio PROCOPIO, Luca VIGANÒ, Matteo DONADON, Guido TORZILLI. Ann Hepatobiliary Pancreat Surg 2022;26:S108. https://doi.org/10.14701/ahbps.2022S1.OP-7-6

Upfront surgery or neoadjuvant chemotherapy for colorectal liver metastases? A machine-learning decision-tree to identify the best potential policy

Upfront surgery or neoadjuvant chemotherapy for colorectal liver metastases? A machine-learning decision-tree to identify the best potential policy

Changes in apparent diffusion coefficient and pathological response in colorectal liver metastases after preoperative chemotherapy.

The pathological response to preoperative chemotherapy of colorectal liver metastases (CRLMs) is predictive of long-term prognosis after liver resection. Accurate preoperative assessment of chemotherapy response could enable treatment optimization. To investigate whether changes in lesion-apparent diffusion coefficient (ADC) measured with diffusion-weighted magnetic resonance imaging (MRI) can be used to assess pathological treatment response in patients with CRLMs undergoing preoperative chemotherapy. Patients who underwent liver resection for CRLMs after preoperative chemotherapy between January 2011 and December 2019 were retrospectively included if they had undergone MRI before and after preoperative chemotherapy on the same 1.5-T MRI scanner with diffusion-weighted imaging with b-values 50, 400, and 800 s/mm2. The pathological chemotherapy response was assessed using the tumor regression grade (TRG) by AJCC/CAP. Lesions were divided into two groups: pathological responding (TRG 0-2) and non-responding (TRG 3). The change in lesion ADC after preoperative chemotherapy was compared between responding and non-responding lesions. A total of 27 patients with 49 CRLMs were included, and 24/49 lesions showed a pathological chemotherapy response. After chemotherapy, ADC increased in both pathological responding (pretreatment ADC: 1.26 [95% confidence interval (CI)=1.06-1.37] vs. post-treatment ADC: 1.33 [95% CI=1.13-1.56] × 10-3 mm2/s; P = 0.026) and non-responding lesions (1.12 [95% CI=0.980-1.21] vs. 1.20 [95% CI=1.09-1.43] × 10-3 mm2/s; P = 0.018). There was no difference in median relative difference in ADC after chemotherapy between pathological responding and non-responding lesions (15.8 [95% CI=1.42-26.3] vs. 7.17 [95% CI=-4.31 to 31.2]%; P = 0.795). Changes in CRLM ADCs did not differ between pathological responding and non-responding lesions.

Can the computed tomography texture analysis of colorectal liver metastases predict the response to first-line cytotoxic chemotherapy?

BACKGROUNDArtificial intelligence in radiology has the potential to assist with the diagnosis, prognostication and therapeutic response prediction of various cancers. A few studies have reported that texture analysis can be helpful in predicting the response to chemotherapy for colorectal liver metastases, however, the results have varied. Necrotic metastases were not clearly excluded in these studies and in most studies the full range of texture analysis features were not evaluated. This study was designed to determine if the computed tomography (CT) texture analysis results of non-necrotic colorectal liver metastases differ from previous reports. A larger range of texture features were also evaluated to identify potential new biomarkers.AIMTo identify potential new imaging biomarkers with CT texture analysis which can predict the response to first-line cytotoxic chemotherapy in non-necrotic colorectal liver metastases (CRLMs).METHODSPatients who presented with CRLMs from 2012 to 2020 were retrospectively selected on the institutional radiology information system of our private radiology practice. The inclusion criteria were non-necrotic CRLMs with a minimum size of 10 mm (diagnosed on archived 1.25 mm portal venous phase CT scans) which were treated with standard first-line cytotoxic chemotherapy (FOLFOX, FOLFIRI, FOLFOXIRI, CAPE-OX, CAPE-IRI or capecitabine). The final study cohort consisted of 29 patients. The treatment response of the CRLMs was classified according to the RECIST 1.1 criteria. By means of CT texture analysis, various first and second order texture features were extracted from a single non-necrotic target CRLM in each responding and non-responding patient. Associations between features and response to chemotherapy were assessed by logistic regression models. The prognostic accuracy of selected features was evaluated by using the area under the curve.RESULTSThere were 15 responders (partial response) and 14 non-responders (7 stable and 7 with progressive disease). The responders presented with a higher number of CRLMs (P = 0.05). In univariable analysis, eight texture features of the responding CRLMs were associated with treatment response, but due to strong correlations among some of the features, only two features, namely minimum histogram gradient intensity and long run low grey level emphasis, were included in the multiple analysis. The area under the receiver operating characteristic curve of the multiple model was 0.80 (95%CI: 0.64 to 0.96), with a sensitivity of 0.73 (95%CI: 0.48 to 0.89) and a specificity of 0.79 (95%CI: 0.52 to 0.92). CONCLUSIONEight first and second order texture features, but particularly minimum histogram gradient intensity and long run low grey level emphasis are significantly correlated with treatment response in non-necrotic CRLMs.

Imaging Disease Biology: A Systematic Review on Radiological Predictors of Response to Chemotherapy in Colorectal Liver Metastasis

Introduction: Pathological response to neoadjuvant chemotherapy in colorectal liver metastases (CRLM) strongly correlates with disease-free and overall survival. While prior clinicopathological predictive models have been described, these provide only an approximation of disease biology. Pre-operative imaging offers a non-invasive morphological and functional assessment of response, with certain parameters outperforming traditional metrics.

Neoadjuvant chemotherapy for colorectal liver metastases: A contemporary review of the literature.

Colorectal carcinoma (CRC) is one of the leading causes of cancer-related deaths worldwide, and up to 50% of patients with CRC develop colorectal liver metastases (CRLM). For these patients, surgical resection remains the only opportunity for cure and long-term survival. Over the past few decades, outcomes of patients with metastatic CRC have improved significantly due to advances in systemic therapy, as well as improvements in operative technique and perioperative care. Chemotherapy in the modern era of oxaliplatin- and irinotecan-containing regimens has been augmented by the introduction of targeted biologics and immunotherapeutic agents. The increasing efficacy of contemporary systemic therapies has led to an expansion in the proportion of patients eligible for curative-intent surgery. Consequently, the use of neoadjuvant strategies is becoming progressively more established. For patients with CRLM, the primary advantage of neoadjuvant chemotherapy (NCT) is the potential to down-stage metastatic disease in order to facilitate hepatic resection. On the other hand, the routine use of NCT for patients with resectable metastases remains controversial, especially given the potential risk of inducing chemotherapy-associated liver injury prior to hepatectomy. Current guidelines recommend upfront surgery in patients with initially resectable disease and low operative risk, reserving NCT for patients with borderline resectable or unresectable disease and high operative risk. Patients undergoing NCT require close monitoring for tumor response and conversion of CRLM to resectability. In light of the growing number of treatment options available to patients with metastatic CRC, it is generally agreed that these patients are best served at tertiary centers with an expert multidisciplinary team.

LBA21 Radioembolization with chemotherapy for colorectal liver metastases: A randomized, open-label, international, multicenter, phase III trial (EPOCH study)

LBA21 Radioembolization with chemotherapy for colorectal liver metastases: A randomized, open-label, international, multicenter, phase III trial (EPOCH study)

Rim enhancement on hepatobiliary phase of pre-treatment 3.0 T MRI: A potential marker for early chemotherapy response in colorectal liver metastases treated with XELOX

PurposeTo assess the value of the enhanced features on the hepatobiliary phase (HBP) of pre-treatment Gd-EOB-DTPA MRI in evaluating response to chemotherapy in colorectal liver metastases (CRLMs). MethodsWe retrospectively studied 65 patients with CRLMs who underwent Gd-EOB-DTPA enhanced MRI before chemotherapy from October 2015 to November 2017. The diagnosis of liver metastasis was established on the basis of imaging findings. Two radiologists evaluated the size, contrast-enhanced (CE) patterns of the maximum lesion on the HBP. According to the different CE patterns, we quantified area signal intensity (SI) by applying SI ratio (such as SIcenter/outer and SIrim/center). All of the above parameters were analyzed in terms of chemotherapy response. ResultsRim enhancement on the HBP was more frequent in the responding group of 28 patients (72%) than in the non-responding group of eight patients (31%). Additionally, there was a significant association between chemotherapy response and quantitative parameters: including diameter (P = 0.04), SIcenter/outer (P = 0.047) and SIrim/center (P = 0.012). The HBP CE pattern (P = 0.007) and SIcenter/outer (P = 0.022) were independent factors for chemotherapy response. The areas under the curve (AUCs) of the above-mentioned parameters were significant associated with response to chemotherapy, in which diameter, HBP CE patterns, SIcenter/outer, and SIrim/center were 0.638, 0.706, 0.712, and 0.673, respectively. Moreover, the combination of these parameters obtained the largest AUC of 0.821. ConclusionThe CE patterns, in particular with rim enhancement, and SI ratio parameters on the HBP are useful indicators for early evaluation of therapeutic response after chemotherapy in patients with CRLMs.

P-252 Residual fibrosis after treatment with anti-epidermal growth factor receptor or bevacizumab in colorectal liver metastases and its correlation with survival: A retrospective pooled analysis

Pathologic response to preoperative chemotherapy for colorectal liver metastases (CLM) is associated with survival after hepatectomy. Rubbia-Brand L et al stablished a five pathological categories classification with prognostic value in this setting. In 2012, Poultsides GA et al concluded that fibrosis, not necrosis, is the predominant chemotherapy-related pathologic alteration driving prognostic information. Stremitzer S et al concluded, in 2015, that cetuximab induces more fibrosis than bevacizumab but did not find differences in overall survival.

Effect of Adding Bevacizumab to Chemotherapy on Pathologic Response to Preoperative Systemic Therapy for Resectable Colorectal Liver Metastases: A Systematic Review and Meta-analysis

BackgroundLiver-limited metastatic colorectal cancer is a potentially curable disease. Pathologic response (pR) to preoperative chemotherapy (CT) for colorectal liver metastases (CLM) is a surrogate endpoint for overall survival (OS). We conducted the first meta-analysis of observational studies to estimate the overall effect of bevacizumab on pR in preoperative systemic therapy for CLM. MethodsWe systematically searched PubMed, Cochrane Library, CINAHL, Web of Science, Embase, and LILACS for studies published between January 2004 and August 2019 that compared the pR of CT plus bevacizumab to CT alone as preoperative therapy for CLM. The primary endpoint was pathologic complete response (pCR). Secondary endpoints were pathologic major (pMaR) and minor (pMiR) response. Overall effects were expressed by odds ratios (ORs) and 95% confidence intervals (CIs) using a random-effects model. ResultsOf the 1,452 studies yielded by the search, 9 were eligible, totaling 1,202 patients (516 CT plus bevacizumab and 686 CT alone). The addition of bevacizumab to CT increased the pCR rate without reaching statistical significance (OR: 1.24, 95% CI 0.81 to 1.92, P = .32). However, pMaR was significantly higher (OR: 2.45, 95% CI 1.85 to 3.25, P < .001), and pMiR was significantly lower (OR: 0.41, 95% CI 0.31 to 0.54, P < .001), in the bevacizumab group. The analyses showed a low level of heterogeneity (I2 = 0% to 6%). Publication bias was not found. ConclusionsThis meta-analysis demonstrates that bevacizumab plus preoperative CT is associated with higher rates of pR in CLM. Antiangiogenics might improve the OS of CLM patients and should be evaluated in randomized clinical trials. MicroAbstractThe benefit of perioperative chemotherapy for colorectal liver metastases (CLM) is uncertain, but pathologic response (pR) to preoperative chemotherapy is a strong prognostic factor. Our meta-analysis of observational studies compared the pR of bevacizumab plus chemotherapy to chemotherapy alone as preoperative systemic therapy in the management of CLM. The addition of bevacizumab was associated with significantly higher rates of pR.

Accuracy of Modern Clinical Risk Score Including RAS Status Changes Based on Whether Patients Received Perioperative Chemotherapy for Colorectal Liver Metastases.

A modified Fong clinical score (m-Fong CS) that includes the RAS mutation status has recently been proposed and offered an improved survival stratification of patients who undergo surgery and systemic chemotherapy for colorectal liver metastases (CLM). The aim of this study is to assess whether a CS that includes RAS status is influenced by whether patients receive perioperative chemotherapy. We created a new CS using multivariate analysis of data of patients who underwent hepatectomy for CLM for the first time between 2010 and 2016 at a single hospital (n = 341, 79% received perioperative chemotherapy). The resulting CS and m-Fong CS were then validated in the patient cohort at three other hospitals (n = 309). Furthermore, the applicability of the two CS in the total cohort (n = 650) was tested according to whether the patients received perioperative chemotherapy. The new CS comprised mutant RAS status, ≥4 CLMs, and a CA19-9 level ≥100U/mL (1 point per factor). Both the new CS and m-Fong CS failed to stratify the survival of the 309 patients in the validation cohort, including those who did not receive perioperative chemotherapy (29%). Both of the CS accurately stratified the survival of patients who underwent perioperative chemotherapy but not of those who underwent surgery alone. A CS that includes the RAS mutation status can stratify the survival of patients who undergo hepatectomy combined with perioperative chemotherapy, but it has limited value for patients who undergo surgery alone.

Radiomics Texture Analysis for the Identification of Colorectal Liver Metastases Sensitive to First-Line Oxaliplatin-Based Chemotherapy.

The aim of this study was to develop a radiomics-based prediction model for the response of colorectal liver metastases to oxaliplatin-based chemotherapy. Forty-two consecutive patients treated with oxaliplatin-based first-line chemotherapy for colorectal liver metastasis at our institution from August 2013 to October 2019 were enrolled in this retrospective study. Overall, 126 liver metastases were chronologically divided into the training (n=94) and validation (n=32) cohorts. Regions of interest were manually segmented, and the best response to chemotherapy was decided based on Response Evaluation Criteria in Solid Tumors (RECIST). Patients who achieved clinical complete and partial response according to RECIST were defined as good responders. Radiomics features were extracted from the pretreatment enhanced computed tomography scans, and a radiomics score was calculated using the least absolute shrinkage and selection operator regression model in a trial cohort. The radiomics score significantly discriminated good responders in both the trial (area under the curve [AUC] 0.8512, 95% confidence interval [CI] 0.7719-0.9305; p<0.0001) and validation (AUC 0.7792, 95% CI 0.6176-0.9407; p<0.0001) cohorts. Multivariate analysis revealed that high radiomics scores greater than -0.06 (odds ratio [OR] 23.803, 95% CI 8.432-80.432; p<0.0001), clinical non-T4 (OR 6.054, 95% CI 2.164-18.394; p=0.0005), and metachronous disease (OR 11.787, 95% CI 2.333-70.833; p=0.0025) were independently associated with good response. Radiomics signatures may be a potential biomarker for the early prediction of chemosensitivity in colorectal liver metastases. This approach may support the treatment strategy for colorectal liver metastasis.