Perioperative Systemic Chemotherapy for Colorectal Liver Metastasis: Recent Updates.
Ontology highlight
ABSTRACT:
SUBMITTER: Lee HY
PROVIDER: S-EPMC8464667 | biostudies-literature | 2021 Sep
REPOSITORIES: biostudies-literature
Publications
Perioperative Systemic Chemotherapy for Colorectal Liver Metastasis: Recent Updates.
Lee Hee Yeon HY Woo In Sook IS
Cancers 20210913 18
The liver is the most common site of metastases for colorectal cancer. Complete resection in some patients with resectable liver metastases (LM) can lead to long-term survival and cure. Adjuvant systemic chemotherapy after complete resection of LM improves recurrence-free survival; however, the overall survival benefit is not clear. In selected patients, preoperative systemic treatment for metastatic colorectal cancer can convert unresectable to resectable cancer. This review will focus on patie ...[more]
Similar Datasets
Project description:The role of perioperative chemotherapy in the management of initially resectable colorectal liver metastases (CRLM) is still unclear. The EPOC trial [the European Organization for Research and Treatment of Cancer (EORTC) 40983] is an important study that declares perioperative chemotherapy as the standard of care for patients with resectable CRLM, and the strategy is widely accepted in western countries. Compared with surgery alone, perioperative FOLFOX therapy significantly increased progression-free survival (PFS) in eligible patients or those with resected CRLM. Overall survival (OS) data from the EPOC trial were recently published in The Lancet Oncology, 2013. Here, we discussed the findings and recommendations from the EORTC 40983 trial.
| S-EPMC4318964 | biostudies-literature
Project description:BackgroundThe liver is the most common site of metastases for colorectal cancer, and combined resection with systemic chemotherapy is the most effective strategy for survival. The aim of this article is to provide a comprehensive summary on four hot topics related to chemotherapy and surgery for colorectal liver metastases (CLM), namely: (1) chemotherapy-related liver injuries: prediction and impact, (2) surgery for initially unresectable CLM, (3) the emerging role of RAS mutations, and (4) the role of hepatic arterial infusion of chemotherapy (HAIC).Summary and key messages(1) The use of chemotherapy before liver resection for CLM leads to drug-specific hepatic toxicity, which negatively impacts posthepatectomy outcomes. (2) Curative liver resection of initially unresectable CLM following conversion chemotherapy should be attempted whenever possible, provided that a safe future liver remnant volume is achieved. (3) For CLM, RAS mutation status is needed to guide the use of targeted chemotherapy with anti-epithelial growth factor receptor (EGFR) agents, and is a major prognostic factor that may contribute to optimize surgical strategy. (4) HAIC agents increase the rate of objective response and the rate of complete pathological response.
| S-EPMC5159720 | biostudies-literature
Project description:The response to preoperative chemotherapy is useful for predicting prognosis in unresectable and resectable disease. However, the prognostic benefit of chemotherapy prior to hepatectomy in patients with colorectal carcinoma and resectable or marginally resectable liver metastases remains unclear. The present study investigated the effect of preoperative chemotherapy on the prognosis of patients with colorectal cancer and resectable or marginally resectable synchronous liver metastasis. A total of 106 patients were retrospectively reviewed, who underwent hepatectomy for colorectal metastasis. The prognosis of 64 patients who received neoadjuvant chemotherapy (NAC) were compared with the 42 patients who did not (non-NAC). Furthermore, a total of 43 patients who responded to chemotherapy were compared with the 21 who did not. Preoperative chemotherapy was administered for 5.7 months, wherein 50 patients (78%) received a single regimen, and 54 (84%) received oxaliplatin. There were more patients with <3 metastases and maximum diameters <5 cm in the non-NAC group. The median survival time was 86.0 and 71.6 months in the NAC and non-NAC groups, respectively (P=0.33). Subgroup analysis on the basis of tumor size and number showed no prognostic differences between the two groups. The median survival time was longer in responders than in non-responders (85 vs. 56 months; P=0.01). However, the median relapse-free survival was equivalent in both groups (16.4 and 10.7 months). Preoperative chemotherapy did not prolong survival. Furthermore, it did not prevent recurrence, even in clinical responders. Therefore, it should not be routinely offered to patients with resectable liver metastasis before their hepatectomy.
| S-EPMC7057917 | biostudies-literature
Project description:BackgroundIt is not known whether perioperative chemotherapy, compared with adjuvant chemotherapy alone, improves disease-free survival (DFS) in patients with upfront resectable colorectal liver metastases (CLM). The aim of this study was to estimate the impact of neoadjuvant 5-fluorouracil, leucovorin and oxaliplatin (FOLFOX) on DFS in patients with upfront resectable CLM.MethodsConsecutive patients who presented with up to five resectable CLM at two Japanese and two French centres in 2008-2015 were included in the study. Both French institutions favoured perioperative FOLFOX, whereas the two Japanese groups systematically preferred upfront surgery plus adjuvant chemotherapy. Inverse probability of treatment weighting (IPTW) and Cox regression multivariable models were used to adjust for confounding. The primary outcome was DFS.ResultsSome 300 patients were included: 151 received perioperative chemotherapy and 149 had upfront surgery plus adjuvant chemotherapy. The weighted 3-year DFS rate was 33·5 per cent after perioperative chemotherapy compared with 27·1 per cent after upfront surgery plus adjuvant chemotherapy (hazard ratio (HR) 0·85, 95 per cent c.i. 0·62 to 1·16; P = 0·318). For the subgroup of 165 patients who received adjuvant FOLFOX successfully (for at least 3 months), the adjusted effect of neoadjuvant chemotherapy was not significant (HR 1·19, 0·74 to 1·90; P = 0·476). No significant effect of neoadjuvant chemotherapy was observed in multivariable regression analysis.ConclusionCompared with adjuvant chemotherapy, perioperative FOLFOX does not improve DFS in patients with resectable CLM, provided adjuvant chemotherapy is given successfully.
| S-EPMC6773651 | biostudies-literature
Project description:Abstract In this review, we focused on four topics, namely, minimally invasive esophagectomy (MIE), robot‐assisted minimally invasive esophagectomy (RAMIE), conversion and salvage surgery, and neoadjuvant and adjuvant therapy, based on notable reports published in the years 2020 and 2021. It seems that while the short‐term outcomes of minimally invasive Ivor Lewis esophagectomy (MIE‐IL) were better than those of open Ivor Lewis esophagectomy (OE‐IL), there were no significant differences in the long‐term outcomes between MIE‐IL and OE‐IL. Similarly, the short‐term outcomes of minimally invasive McKeown esophagectomy (MIE‐MK) were better than those of open McKeown esophagectomy (OE‐MK), while there were no significant differences in the long‐term outcomes between MIE‐MK and OE‐MK. Furthermore, the short‐term outcomes of robot‐assisted minimally invasive Ivor Lewis esophagectomy (RAMIE‐IL) were superior to those of completely minimally invasive Ivor Lewis esophagectomy (CMIE‐IL). On the other hand, there were advantages and disadvantages in relation to the short‐term outcomes of robot‐assisted minimally invasive McKeown esophagectomy (RAMIE‐MK) as compared with completely minimally invasive McKeown esophagectomy (CMIE‐MK). However, there were no significant differences in the long‐term outcomes between RAMIE‐MK and CMIE‐MK. Further research is needed to evaluate of short‐term and long‐term outcomes of transmediastinal esophagectomy with and without robotic assistance. Both induction chemotherapy and induction chemoradiotherapy appear to be promising to secure a higher rate of conversion surgery. Neoadjuvant chemoimmunotherapy and chemoimmunoradiotherapy have shown promising results and are expected as new powerful therapies. There were advantages and disadvantages in relation to the short‐term outcomes of robot‐assisted minimally invasive McKeown esophagectomy (RAMIE‐MK) as compared with completely minimally invasive McKeown esophagectomy (CMIE‐MK). However, there were no significant differences in the long‐term outcomes between RAMIE‐MK and CMIE‐MK. The short‐term and mid‐term outcomes between robot‐assisted minimally invasive transmediastinal esophagectomy (RATME) and open transmediastinal esophagectomy (OTME) were also compared. Although RATME has some disadvantages, such as a higher rate of pulmonary complications as compared with OTME, these are expected to be overcome in the future.
| S-EPMC10154818 | biostudies-literature
Project description:Nonalcoholic fatty liver disease (NAFLD), together with metabolic syndrome and obesity, has shown a rapid increase in prevalence worldwide and is emerging as a major cause of chronic liver disease and liver transplantation. Among the various phenotypes of NAFLD, nonalcoholic steatohepatitis (NASH) is highly likely to progress to development of end-stage liver disease and cardiometabolic disease, resulting in liver-related and non-liver-related mortality. Nonetheless, there is no standardized pharmacotherapy against NASH and many drugs are under development in ongoing clinical trials. To develop a successful anti-NASH drug, it is necessary to select an appropriate target population and treatment outcomes depending on whether the mode of action is anti-metabolic, anti-inflammatory or anti-fibrotic. Recently, innovative surrogate markers have been investigated to replace hard outcomes such as liver histology and mortality and reduce the clinical trial duration. Currently, several drugs with fast track designation are being tested in phase III clinical trials, and many other drugs have moved into phase II clinical trials. Both lean NAFLD and typical obese NAFLD have been extensively studied and genetic variants such as PNPLA3 and TM6SF2 have been identified as significant risk factors for lean NAFLD. In the near future, noninvasive biomarkers and effective targeted therapies for NASH and associated fibrosis are required to develop precision medicine and tailored therapy according to various phenotypes of NAFLD.
| S-EPMC6435971 | biostudies-literature
Project description:IntroductionIn stage IV NSCLC with solitary or oligometastatic brain metastasis, surgical resection of the primary and definitive management of the brain metastasis is an accepted standard. However, the effect of systemic chemotherapy after surgical resection on overall survival is not well-established.MethodsWe used the National Cancer Database to retrospectively identify individuals with NSCLC as the primary tumor along with synchronous brain metastases who underwent thoracic resection with or without adjuvant chemotherapy. Chi-square and Wilcoxon rank sum tests were performed to compare categorical and continuous variables, respectively, across the treatment groups. Kaplan-Meier and Cox proportional modeling were done to determine the survival benefit.ResultsA total of 310 (71.9%) of the cohort received perioperative chemotherapy, most of whom (79.4%) received it in the adjuvant setting. Patients receiving chemotherapy were likely to be younger (p = 0.002), privately insured (p = 0.01), and receive radiation (p < 0.001). Perioperative chemotherapy was significantly associated with survival on both univariate (hazard ratio = 0.71[0.52 - 0.99]) and multivariable (hazard ratio = 0.66 [0.47 - 0.92]) in addition to age (p = 0.03), Charlson-Deyo score (p = 0.02), pathologic N stage (p = 0.02), and adenocarcinoma histology (p = 0.02). Kaplan-Meier analysis confirmed this result with a significantly better survival with perioperative chemotherapy (p = 0.02). Further subgroup analysis using pathologic N stage revealed similar effect in pN1 (p = 0.001), but not pN0 (p = 0.2) patients.ConclusionsPerioperative chemotherapy for pN0-1 NSCLC with synchronous brain metastasis is associated with improved OS in this analysis.
| S-EPMC10238748 | biostudies-literature
Project description:Histopathological growth patterns (HGPs) are a reliable, reproducible, and strong prognostic biomarker that can be assessed on haematoxylin and eosin-stained sections of resected colorectal liver metastases (CRLM). Assessment estimates the relative fraction of the tumour-liver interface for each of the three growth patterns; the desmoplastic HGP reflects good prognosis. Whether preoperative chemotherapy affects the HGP is currently unclear. The present international multicentre study evaluates this in an original cohort of 877 consecutive patients treated in the Netherlands, an external validation cohort of 1,203 consecutive patients treated in the USA, and a post hoc analysis from the phase III randomised controlled European Organization for Research and Treatment of Cancer (EORTC) 40983 trial (n = 70). All patients underwent resection of CRLM with or without preoperative systemic chemotherapy. Trial patients were randomised between perioperative chemotherapy and resection or resection alone. HGPs were determined according to consensus guidelines and compared for preoperative treatment status. Data from three separate tumour regression grading systems were available for the trial cohort. These were correlated with HGP stratified for treatment arm. In the original cohort, the average presence of desmoplastic HGP was 43% for chemo-naïve versus 67% for preoperatively treated patients (p < 0.001). A significant association between chemotherapy and desmoplastic HGP was found on multivariable analysis (β [95% confidence interval, CI]: 24.57 [18.28-30.87], p < 0.001). In the validation cohort, the average presence of desmoplastic HGP was 40% for chemo-naïve versus 63% for preoperatively treated patients (p < 0.001). This association remained on multivariable analysis (β [95% CI]: 24.18 [18.70-29.66], p < 0.001). In the EORTC 40983 trial, the average desmoplastic HGP presence was 33% in the resection arm versus 61% in the chemotherapy arm (p = 0.005). Chemotherapy was independently associated with an increase in desmoplastic HGP (β [95% CI]: 23.29 [1.78-44.79], p = 0.022). All three tumour regression gradings were significantly associated with the desmoplastic HGP in the chemotherapy arm (all p < 0.04). None were associated in the resection arm (all p > 0.11). Preoperative chemotherapy induces histopathological changes that alter the HGP of CRLM.
| S-EPMC8682940 | biostudies-literature
Project description:Colorectal cancer is a leading cause of cancer-related mortality worldwide. Approximately 3-5% of colorectal tumors harbor human epidermal growth factor receptor (HER2) amplification which is associated with a higher incidence of intracranial metastasis and overall worse outcomes. In the setting of refractory metastatic RAS wild-type tumors, evidence supports the use of various HER2-blocking agents, including monoclonal antibodies, tyrosine kinase inhibitors, and novel antibody-drug conjugates. With a number of relatively active agents clinically available and even more in development, it is crucial for clinicians to familiarize themselves with the mechanisms of action, efficacy data, and safety profiles of these treatments. In this review, we aim to summarize key findings from past and ongoing trials with anti-HER2 agents in metastatic colorectal cancer.
| S-EPMC10798128 | biostudies-literature
Project description:Disease progression (PD) at neoadjuvant chemotherapy for patients with colorectal liver metastases (CLMs) is considered a contraindication to hepatic resection. Our aim was to estimate the overall survival (OS) in patients undergoing surgery compared with those treated exclusively with chemotherapy in cases of PD. Patients from a single centre with PD were analyzed and subdivided into two groups: hepatectomy (HEP) versus chemotherapy (CHT). An Inverse Probability Weighting (IPW) was run to balance the baseline differences between the two groups. A Cox regression was carried out on identifying factors predicting mortality. From 2010 to 2020, 105 patients in PD to at least one line of chemotherapy were analyzed. Of these, 27 (25.7%) underwent hepatic resection. After a median follow-up of 30 (IQR 14-46) months, 61.9% were dead. The OS values at 1 and 3 years were 54.4 and 10.6% for CHT, and 95 and 46.8% for HEP (p < 0.001). After IPW, two balanced pseudopopulations were obtained: HEP = 85 and CHT = 103. The OS values at 1 and 3 years were 54.4 and 10.6% for CHT, and 97.8 and 49.3% for HEP (HR 0.256, 95%CI: 0.08-0.78, p = 0.033). After IPW, in the multivariate model, surgery resulted in the only protective variable (HR 0.198, 95%CI: 0.08-0.48, p = 0.0016). Our results show that hepatic resection could offer a chance of a longer OS than the prosecution of chemotherapy only in originally resectable patients.
| S-EPMC9913571 | biostudies-literature