Management Of Liver Metastases Research Articles

From biology to the clinic - exploring liver metastasis in prostate cancer.

Liver metastases from prostate cancer are associated with an aggressive disease course and poor prognosis. Results from autopsy studies indicate a liver metastasis prevalence of up to 25% in patients with advanced prostate cancer. Population data estimate that ~3-10% of patients with metastatic castration-resistant prostate cancer harbour liver metastases at the baseline, rising to 20-30% in post-treatment cohorts, suggesting that selective pressure imposed by novel therapies might promote metastatic spread to the liver. Liver metastases are associated with more aggressive tumour biology than lung metastases. Molecular profiling of liver lesions showed an enrichment of low androgen receptor, neuroendocrine phenotypes and high genomic instability. Despite advancements in molecular imaging modalities such as prostate-specific membrane antigen PET-CT, and liquid biopsy markers such as circulating tumour DNA, early detection of liver metastases from prostate cancer remains challenging, as both approaches are hampered by false positive and false negativeresults, impeding the accurate identification of early liver lesions. Current therapeutic strategies showed limited efficacy in this patient population. Emerging targeted radionuclide therapies, metastasis-directed therapy, and novel systemic agents have shown preliminary activity against liver metastases, but require further validation. Treatment with various novel prostate cancer therapies might lead to an increase in the prevalence of liver metastasis, underscoring the urgent need for coordinated efforts across preclinical and clinical researchers to improve characterization, monitoring, and management of liver metastases from prostate cancer. Elucidating molecular drivers of liver tropism and interactions with the liver microenvironment might ultimately help to identify actionable targets to enhance survival in this high-risk patient group.

Consensus of recommendations in management of liver metastasis from colorectal cancer

Consensus of recommendations in management of liver metastasis from colorectal cancer

Efficacy and adverse reaction management of oncolytic viral intervention combined with chemotherapy in patients with liver metastasis of gastrointestinal malignancy.

The liver is a key target organ for colorectal and gastric cancer metastasis. One of the challenges in the treatment of colorectal and gastric cancers is the management of liver metastasis. This study aimed to investigate the efficacy, adverse effects, and coping strategies of oncolytic virus injection in patients with liver metastases of gastrointestinal malignancies. We prospectively analyzed patients treated at Ruijin Hospital affiliated with Shanghai Jiao Tong University School of Medicine from June 2021 to October 2022. 47 patients with gastrointestinal cancer liver metastasis were included in the study. The data, including clinical manifestations, imaging, tumor markers, postoperative adverse reactions, psychological intervention, dietary guidance, and adverse reaction management were evaluated. Oncolytic virus injection was successful in all patients, and no drug injection-related deaths occurred. The adverse effects, such as fever, pain, bone marrow suppression, nausea, and vomiting, were mild and resolved subsequently. Based on the comprehensive intervention of nursing procedures, the postoperative adverse reactions of patients were effectively alleviated and treated. None of the 47 patients had any puncture point infections, and the pain caused by the invasive operation was relieved quickly. After 2 courses of oncolytic virus injection, postoperative liver MRI showed 5 partial remissions, 30 stable diseases, and 12 progressive diseases in target organs. Interventions based on nursing procedures can ensure the smooth treatment of recombinant human adenovirus type 5 in patients with liver metastases of gastrointestinal malignant tumors. This is of great importance for clinical treatment and significantly reduces patient complications and improves the patient's quality of life.

The Role of Stereotactic Body Radiation Therapy in the Management of Liver Metastases

The liver is a common site for metastatic spread for various primary tumor histologies. Stereotactic body radiation therapy (SBRT) is a non-invasive treatment technique with broad patient candidacy for the ablation of tumors in the liver and other organs. SBRT involves focused, high-dose radiation therapy delivered in one to several treatments, resulting in high rates of local control. Use of SBRT for ablation of oligometastatic disease has increased in recent years and emerging prospective data have demonstrated improvements in progression free and overall survival in some settings. When delivering SBRT to liver metastases, clinicians must balance the priorities of delivering ablative tumor dosing while respecting dose constraints to surrounding organs at risk (OARs). Motion management techniques are crucial for meeting dose constraints, ensuring low rates of toxicity, maintaining quality of life, and can allow for dose escalation. Advanced radiotherapy delivery approaches including proton therapy, robotic radiotherapy, and real-time MR-guided radiotherapy may further improve the accuracy of liver SBRT. In this article, we review the rationale for oligometastases ablation, the clinical outcomes with liver SBRT, tumor dose and OAR considerations, and evolving strategies to improve liver SBRT delivery.

Expert recommendations about the use of gadoxetic acid in patients with liver metastases in Spain

Background and aimsMagnetic resonance imaging (MRI) with gadoxetic acid is widely used in clinical practice in Spain for the diagnosis, treatment, and follow-up of patients with liver metastases, although its use varies. This paper aims to provide recommendations for the use of MRI with gadoxetic acid in the detection and diagnosis of liver metastases in clinical practice in Spain. Material and methodsThis project was undertaken by a group of nine experts who analyzed a series of recommendations about the use of gadoxetic acid extracted from international consensus documents. From this analysis, the experts decided to reject, adopt, contextualize, or adapt each of the recommendations. Once established, the final recommendations were voted on by the same group of experts. ResultsThe experts reached a consensus about five recommendations related to the use of this imaging technique in the management of liver metastases in three clinical situations: (i) in the detection, (ii) in the diagnosis and preoperative characterization, and (iii) in the detection after a chemotherapy treatment. ConclusionThe results support a clinical benefit for MRI with gadoxetic acid in the detection of liver metastases, favoring preoperative planning, especially in metastases measuring less than 1 cm, thus facilitating early diagnosis of metastatic spread.

Role of Surgery in the Management of Liver Metastases From Gastrointestinal Stromal Tumors.

BackgroundThe clinical benefit of hepatectomy in patients with liver metastases from gastrointestinal stromal tumors (GIST) has not been well defined in this era of tyrosine kinase inhibitor (TKI). Our study aims to demonstrate the survival advantage of adding hepatectomy in patients with GIST liver metastases.MethodsInformation on patients with metastatic GIST treated or consulted between January 2006 and December 2018 was retrieved. Patients without extrahepatic metastases were included and classified into the surgical (S group) and non-surgical (NS group). Clinicopathological features were compared and their association with survival was assessed.ResultsA total of 119 patients were included in this retrospective analysis, 62 in the S group and 59 in the NS group. Comparison of clinicopathological features showed that a markedly higher proportion of patients in the S group had ≤3 hepatic lesions (79.0% vs. 29.8%, p<0.001). After a median follow-up duration of 56 months, patients in the S group had significantly better progression-free survival (PFS) and marginally improved overall survival (OS) than those in the NS group (3y PFS:86.2% vs. 64.6%, p=0.002; 5y OS: 91.5% vs. 78.3%, p=0.083). After propensity score matching, multivariate analysis identified hepatectomy as the only significant prognostic factor for PFS while age, hepatectomy and max tumor diameter were significant predictor for OS.ConclusionsAddition of hepatectomy provided longer disease control in patients with metastatic GIST confined to the liver. Upfront hepatectomy followed by imatinib therapy is worthwhile trying in patients with single and easily removable lesions.

Recomendaciones de expertos sobre el uso de ácido gadoxético en pacientes con metástasis hepáticas en España

Background and aimsMagnetic resonance imaging (MRI) with gadoxetic acid is widely used in clinical practice in Spain for the diagnosis, treatment, and follow-up of patients with liver metastases, although its use varies. This paper aims to provide recommendations for the use of MRI with gadoxetic acid in the detection and diagnosis of liver metastases in clinical practice in Spain. Material and methodsThis project was undertaken by a group of nine experts who analyzed a series of recommendations about the use of gadoxetic acid extracted from international consensus documents. From this analysis, the experts decided to reject, adopt, contextualize, or adapt each of the recommendations. Once established, the final recommendations were voted on by the same group of experts. ResultsThe experts reached a consensus about five recommendations related to the use of this imaging technique in the management of liver metastases in three clinical situations: (i) in the detection, (ii) in the diagnosis and preoperative characterization, and (iii) in the detection after a chemotherapy treatment. ConclusionThe results support a clinical benefit for MRI with gadoxetic acid in the detection of liver metastases, favoring preoperative planning, especially in metastases measuring less than 1cm, thus facilitating early diagnosis of metastatic spread.

Colorectal Cancer, Liver Metastases and Biotherapies

(1) Background: colorectal cancer (CRC) is one of the deadliest causes of death by cancer worldwide. Its first main metastatic diffusion spreads to the liver. Different mechanisms such as the epithelial–mesenchymal transition and angiogenesis are the characteristics of this invasion. At this stage, different options are possible and still in debate, especially regarding the use of targeted therapeutics and biotherapies. (2) Methods: A review of the literature has been done focusing on the clinical management of liver metastasis of colorectal cancer and the contribution of biotherapies in this field. (3) Results: In a clinical setting, surgeons and oncologists consider liver metastasis in CRC into two groups to launch adapted therapeutics: resectable and non-resectable. Around these two entities, the combination of targeted therapies and biotherapies are of high interest and are currently tested to know in which molecular and clinical conditions they have to be applied to impact positively both on survival and quality of life of patients.

Can radiotherapy finally “go live” in the management of liver metastases?

Can radiotherapy finally “go live” in the management of liver metastases?

Stereotactic body radiation therapy for liver metastases: Clinical outcomes and literature review.

The role of stereotactic body radiation therapy (SBRT) in the management of liver metastasis is increasing, using ablative doses with the goal of local control and ultimately improving survival. The aim of this study is to evaluate our initial results regarding local control, overall survival and toxicity in patients with liver metastases treated with this technique, due to the lack of evidence reported in Latin America. We performed a retrospective chart review from November 2012 to June 2018 of 24 patients with 32 liver metastases. Kaplan-Meier curves were constructed for local control and overall survival. Clinical and prognostic factors were further analyzed by independent analysis. Median follow-up period was 22 months (range, 1-65 months). Median age was 62 years (range, 40-84 years). Colorectal carcinoma was the most common primary cancer. Overall 1-year and 2-years local control rates were 82% (95% Confidence Interval [CI], 70-98%) and 76.2% (95% CI, 45-90%), respectively. Median overall survival rate was 35 months (95%, CI 20.5-48 months). Overall 1-year and 2-year survival rates were 85.83% (95% CI, 64-99%) and 68% (95% CI, 45-84%), respectively. No acute or late grade 3 or 4 toxicity was observed during the follow-up period. SBRT achieves excellent local control and overall survival rates with low toxicity in patients with liver metastases. Based on our literature review, our results are consistent with larger reports. Further randomized trials are required to compare with other local therapies.

Surgical management of metastatic gastric cancer: moving beyond the guidelines.

Despite decreasing incidence, gastric cancer remains a major health problem worldwide and is associated with poor survival. The poor survival is mainly attributed to delayed presentation which may cause local or systemic metastases. The standard of care for patients with metastatic gastric cancer (MGC) is palliative chemotherapy with best supportive care. Although the survival has improved owing to advances in chemotherapeutic agents, it is still unsatisfactory, and some perspective changes are needed in the management of MGC to improve the outcomes. Therefore, various alternative treatment strategies for MGC have formed the most important research topics. Liver-directed treatment (LDT) options such as liver resection, radiofrequency ablation (RFA), microwave ablation (MWA), and hepatic artery infusion chemotherapy (HAIC) have been studied in the management of liver metastasis from gastric cancer (LMGC). Intraperitoneal chemotherapy (IPC) in addition to cytoreductive surgery (CRS) aiming to remove all macroscopic tumor focus resulting from peritoneal dissemination is the treatment option for peritoneal metastasis, while para-aortic lymph node dissection is the treatment option for para-aortic lymph node metastasis which is considered to be M1 disease. Conversion surgery is a novel concept aiming at R0 resection for originally unresectable or marginally resectable tumors after a remarkably good response to the chemotherapy. Large amounts of data in the literature have demonstrated the benefits of individualized approaches such as the combination of systemic and local treatment options in selected patient groups. In this review, we aimed to explore the current and future treatment options by reviewing the literature on this controversial topic.

Current Trends in the Surgical Management of Colorectal Cancer Liver Metastases

Cancers of colorectal origin are the second leading cause of cancer-related deaths in the USA, and with the improvements in chemotherapy and other therapeutic modalities, there are more options for the management of metastatic disease. The liver is the most common site of colorectal metastasis, and treating the disease to the liver may lead to prolonged survival and possible cure. Our understanding of tumor biology and the refinement of surgical techniques have resulted in significantly improved outcomes. The treatment of colorectal liver metastasis is complex and thus requires a multidisciplinary approach. There is increasing body of literature that points towards more aggressively selective and personalized surgical treatment of colorectal cancer liver metastases. New techniques like hepatic artery infusion, liver chemoperfusion, operative and transcutaneous liver ablation with microwave, radiofrequency or irreversible electroporation have resulted in significantly improved outcomes. There is significant progress in the surgical management of liver metastasis of colorectal origin, with improved outcomes in patients that otherwise would be candidates only for palliative chemotherapy. More and exciting research is underway in order to appreciate the impact of newer techniques.

Analysis of Response Evaluation Criteria in Solid Tumors reduction ratio of primary chemotherapy in unresectable advanced or recurrent colorectal cancer.

Response Evaluation Criteria in Solid Tumors (RECIST) is used to assess the objective response of solid tumors to treatment. However, it remains unclear to what extent the response rate assessed by RECIST reflects a reduction of tumor size in multiple organs in patients with unresectable advanced or recurrent colorectal cancer (CRC) with multiple organ metastases. It is also unclear whether the management of liver metastases with systemic chemotherapy in CRC patients with multiple organ metastases improves their prognosis, although surgical resection has been shown to be the most effective treatment approach to CRC cases with liver metastases. A total of 38 CRC patients who underwent systemic chemotherapy in Kyushu Medical Center Hospital between January 2013 and April 2016 were examined. The patients had measurable lesions in multiple organs, including the liver, and did not undergo curative surgery for metastatic lesions after initiation of chemotherapy. The association between the total reduction ratio (TRR) of all lesions and liver lesion reduction ratio (LRR) was retrospectively analyzed. A total of 18 patients (47%) had H3 liver metastases, and the median liver lesion occupancy rate in the sum of the measured lesions with RECIST was 76%. TRR and LRR were strongly correlated, regardless of the volume of the liver metastases. Although a TRR of >30% was significantly associated with improved overall survival (OS), this improvement was not observed in patients with H3 liver metastases. TRR was correlated with LRR and was associated with a better OS. CRC patients with both multiple organ and H3 liver metastases exhibited poor survival, even with a high reduction ratio by chemotherapy.

Gastrectomy Alone or in Combination With Hepatic Resection in the Management of Liver Metastases From Gastric Cancer: A Systematic Review Using an Updated and Cumulative Meta-Analysis.

BackgroundRecent studies have demonstrated that hepatectomy in patients with synchronous hepatic gastric metastases may improve survival in certain patients. This study aimed to evaluate survival benefits of gastrectomy plus hepatectomy versus gastrectomy alone in patients with hepatic gastric metastases.MethodsStudies were identified by a systematic search of Embase, PubMed, Cochrane Library, and Google Scholar databases. Traditional and cumulative meta-analyses were used to monitor the evidence over time.ResultsEleven studies which included 861 patients compared gastrectomy plus hepatic resection in 349 patients with gastrectomy alone in 512 patients. Overall significantly better survival rates of 1, 2, 3, and 5 years were demonstrated for patients who underwent gastrectomy plus hepatic resection compared to patients who under underwent gastrectomy alone ((hazard ratio (HR) = 0.52 (0.39, 0.69), P < 0.001), (HR = 0.85 (0.74, 0.97), P = 0.01), (HR = 0.80 (0.72, 0.90), P = 0.003), (HR = 0.83 (0.78, 0.90), P < 0.001), respectively).ConclusionsCarefully selected patients with hepatic gastric metastases may benefit from hepatic resection.

My burning issues in the management of liver metastases of advanced colorectal cancer

My burning issues in the management of liver metastases of advanced colorectal cancer

Role of surgery in pancreatic neuroendocrine tumor.

Pancreatic neuroendocrine tumours (PNETs) are rare. They are generally accepted to be slow-growing and have an indolent course. These tumours can be non-functioning or functioning, consisting of a biochemically heterogeneous group of tumours including insulinomas, gastrinomas, carcinoids and glucagonomas. Although surgery remains the mainstay of treatment, controversy still exists especially for non-functioning tumours <2 cm in size. Whether these should be resected or undergo intensive surveillance remains unclear. The surgical approach depends on local expertise. Many studies have shown comparable short-term surgical outcome with laparoscopic pancreatic resection compared to open techniques, however data on long-term oncological outcome are still lacking. On the other hand, liver metastasis occurs in as high as 80% of PNET patients. Five-year survival rate is only 30% if left untreated compared to 60-80% if complete resection is achieved. Current evidence supports liver resection with an aim for symptomatic control and to improve survival in those with respectable disease and no extra-hepatic metastasis. Palliative debunking can be considered in those with intractable symptoms. This article reviews the current evidence on pancreatic resection for PNETs, in particular the role of laparoscopic resection and the management of liver metastasis.

Malignant Renal Epithelioid Angiomyolipoma with Liver Metastases Managed with Transarterial Chemoembolization (TACE): A Rare Case Report and Review

Renal epithelioid angiomyolipoma (EAML) is a rare tumor with the potential for malignant metastasis. EAML with local invasion is radiologically difficult to differentiate from renal cell carcinoma (RCC). The treatment of choice is surgery and there is no known effective management dealing with distant metastases. This case report described the imaging features of EAML and assessed the efficacy of TACE for the management of liver metastases, which, to our knowledge, no previous literature had addressed this issue.

Prognostic factors influencing survival in small bowel neuroendocrine tumors with liver metastasis.

e15688 Background: Management of liver metastasis in patients with small bowel neuroendocrine tumors (SBNET) remains unclear. Complete surgical resection improves long term survival however factors that influence overall prognosis are not clear. Methods: Database review identified 301 patients diagnosed with SBNET from 1990 to 2013. Only patients with known liver metastasis who underwent resection of the primary tumor were included. Outcomes among patients who underwent complete surgical resection, incomplete debulking of liver metastasis, and resection of the primary tumor alone were compared. The Kaplan-Meier method was used for survival estimates and Cox regression was used to identify predictors of death. Results: 111 patients met study criteria. Median age was 59 years (range 16-80); 49% were male. The terminal ileum (47/111, 42%) was the most common primary tumor location. The median number of liver lesions was 8.5 (range 1-31) and median lesions resected was 1 (range 0-31). In addition to resection of the primary tumor, 36 patients (32%) had no liver resection (NR), 41 (36.9%) had complete resection of liver disease (R0) and 34 (30%) had incomplete resection of liver metastasis (R1). 58 patients (36%) had one or more wedge resections, 12 (10.8%) underwent segmentectomy and 5 (4.5%) had a lobectomy. 33 (29.7%) patients underwent post-operative chemoembolization, 25 (22.5%) had radioembolization and 23 (20.7%) had radiofrequency ablation. The R1 group differed from the R0 group in median size of primary tumor (2.5 cm R1 vs 1.6 cm R0, p = 0.05) and median number of positive lymph nodes (5.0 R1 vs 3.0 R0, p = 0.05). The 5-year OS was 80.9%, 81.1% and 100% for NR, R1 and R0 groups respectively (p = 0.01). 10-year OS did not differ between groups (72.8% NR vs 81.1% R1vs 82.5% NR, p = 0.31). Cox regression showed post-operative administration of chemotherapy (HR = 3.68, p &lt; 0.01) and higher tumor grade (HR = 18.4, p = 0.02) increased risk of death. Conclusions: In patients with SBNET with liver metastasis, higher tumor grade and post-operative chemotherapy increased risk of death. However, resection of the primary tumor along with liver metastasis improves the 5-year OS with complete cytoreduction providing the most benefit.

Hepatectomy for liver metastases from gastric cancer: a systematic review

BackgroundOfficial guidelines recommend palliative treatments for patients with liver metastases from gastric cancer. However, many case series reported that hepatectomy for such cases is safe and effective. This systematic review compares the overall survival between hepatectomy and palliative therapy in patients with liver metastases from gastric cancer.MethodsTwo independent reviewers performed a systematic search of literature in EMBASE and PubMed, updated until 26 October 2016. The Newcastle-Ottawa score for cohort studies was used for quality assessment of included studies.ResultsA total of eight cohort studies involving 196 patients in the hepatectomy arm and 481 in the palliative arm were included. Median overall survival of patients in the two arms was 23.7 (range, 13.0 to 48.0) and 7.6 (range, 5.5 to 15.2), respectively. Median rates of overall survival of the two arms were 69, 40, 33 and 27, 8, 4% at 1, 2, and 3 years, respectively. Comparing with palliative therapy, hepatectomy was associated with significantly lower mortality at 1 year (odds ratio 0.17, P < 0.001) and 2 years (odds ratio 0.15, P < 0.001). Among the patients who underwent hepatectomy, Asian cohorts showed higher median rates of overall survival than Western cohorts at 1 year (76 vs. 60%), 2 years (47 vs. 30%) and 3 years (39 vs. 23%).ConclusionsHepatectomy in the management of liver metastases from gastric cancer can be considered effective. In the elective setting, hepatectomy provides a potential alternative to palliative therapy.

Advances in the diagnosis and treatment of pancreatic neuroendocrine neoplasms in Japan.

Several new developments have occurred in the field of pancreatic neuroendocrine neoplasm (PNEN) recently in Japan. First, the utility of chromogranin A (CgA), useful for the diagnosis and monitoring of the treatment response of neuroendocrine neoplasm (NEN), has been demonstrated in Japan. For PNEN diagnosis and treatment, grading and correct histological diagnosis according to the WHO 2010 classification is important. Regarding the histological diagnosis, the advent of endoscopic ultrasonography-guided fine-needle aspiration (EUS-FNA) has enabled correct pathological diagnosis and suitable treatment for the affected tissue. Furthermore, EUS-FNA has also facilitates the assessment of the presence or absence of gene mutations. In addition, patients who have a well-differentiated neuroendocrine tumor (NET) showing a Ki-67 index of higher than 20% according to the WHO 2010 classification, have also been identified, and their responses to treatment were found to be different from those of patients with poorly differentiated neuroendocrine carcinoma (NEC). Therefore, the concept of NET G3 was proposed. Additionally, somatostatin receptor type 2 is expressed in several cases of NET, and somatostatin receptor scintigraphy (111In-octreoscan) has also been approved in Japan. This advancement will undoubtedly contribute to the localization diagnosis, the identification of remote metastasis, and assessments of the treatment responses of PNEN. Finally, regarding the treatment strategy for PNEN, the management of liver metastasis is important. The advent of novel molecular-targeted agents has dramatically improved the prognosis of advanced PNEN. Multimodality therapy that accounts for the tumor stage, degree of tumor differentiation, tumor volume, and speed of tumor growth is required.