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Background: In recent years, the incidence of patients with colorectal neuroendocrine neoplasms (CRNENs) has been continuously increasing. When diagnosed, most patients have distant metastases. Liver metastasis (LM) is the most common type of distant metastasis, and the prognosis is poor once it occurs. However, there is still a lack of large studies on the risk and prognosis of LM in CRNENs. This study aims to identify factors related to LM and prognosis and to develop a predictive model accordingly. Methods: In this study, the Surveillance, Epidemiology, and End Results (SEER) database was used to collect clinical data from patients with CRNENs. The logistic regression analyses were conducted to identify factors associated with LM in patients with CRNENs. The patients with LM formed the prognostic cohort, and Cox regression analyses were performed to evaluate prognostic factors in patients with liver metastasis of colorectal neuroendocrine neoplasms (LM-CRNENs). Predictive and prognostic nomogram models were constructed based on the multivariate logistic and Cox analysis results. Finally, the capabilities of the nomogram models were verified through model assessment metrics, including the receiver operating characteristic (ROC) curves, calibration curve, and decision curve analysis (DCA) curve. Results: This study ultimately encompassed a total of 10,260 patients with CRNENs. Among these patients, 501 cases developed LM. The result of multivariate logistic regression analyses indicated that histologic type, tumor grade, T stage, N stage, lung metastasis, bone metastasis, and tumor size were independent predictive factors for LM in patients with CRNENs (p < 0.05). Multivariate Cox regression analyses indicated that age, primary tumor site, histologic type, tumor grade, N stage, tumor size, chemotherapy, and surgery were independent prognostic factors (p < 0.05) for patients with LM-CRNENs. The predictive and prognostic nomogram models were established based on the independent factors of logistic and Cox analyses. The nomogram models can provide higher accuracy and efficacy in predicting the probability of LM in patients with CRNENs and the prognosis of patients with LM. Conclusion: The factors associated with the occurrence of LM in CRNENs were identified. On the other hand, the relevant prognostic factors for patients with LM-CRNENs were also demonstrated. The nomogram models, based on independent factors, demonstrate greater efficiency and accuracy, promising to provide clinical interventions and decision-making support for patients. [ABSTRACT FROM AUTHOR]

Introduction: Surgical resection is gold standard for treatment of liver metastasis, locally ablative techniques including computer tomography (CT)-guided interstitial high-dose-rate (HDR) brachytherapy (CT-BRT) and stereotactic body radiotherapy (SBRT) have gained prominence as alternatives, offering comparable outcomes in selected patients. We aim to compare CT-BRT and SBRT - based on dosimetric analysis. Material and methods: Patients who underwent CT-BRT for oligometastatic, ≤4cm liver metastases between 2018 and 2024 were eligible. SBRT plans for Halcyon (SBRTh) and TrueBeam (SBRTtb) were prepared virtually. In the CT-BRT group CTV was equal to PTV, for SBRTh and SBRTtb planning, a 5 mm margin was applied to CTV to create PTV. Dose calculation was carried out with the TG-43 algorithm for CT-BRT and Anisotropic Analytical Algorithm for SBRTh and SBRTtb group. Descriptive statistics were used to compare the data. The Wilcoxon pairwise order test was utilized to compare dependent groups. Results: CT-BRT resulted in a more favorable dose distribution within PTVs for Dmean, D50, and D90, while SBRT showed better results for D98 and V27.5Gy. No significant differences were observed for V25Gy between CT-BRT and SBRTtb, but SBRTh favored over CT-BRT. For OARs, CT-BRT plans showed better values for V5, V10, and V11.6Gy in the uninvolved liver volume. There were no significant differences in dose distribution for the duodenum, bowel, and heart. SBRT modalities performed better in the kidney. CT-BRT had improved dose distribution in the esophagus, great vessels, ribs, skin, spinal cord, and stomach compared to SBRT. Conclusions: CT-BRT could be a viable alternative to SBRT for certain patients with liver malignancies. [ABSTRACT FROM AUTHOR]

Background: The liver is a frequent location of metastatic disease in various malignant tumor entities. Computed tomography (CT) is the most frequently employed modality for initial diagnosis. However, liver metastases may only be delineated vaguely on CT. Calculating radiomics features in feature maps can unravel textures not visible to the human eye on a standard CT reconstruction (SCTR). This study aimed to investigate the comparative diagnostic accuracy of radiomics feature maps and SCTR for liver metastases. Materials and methods: Forty-seven patients with hepatic metastatic colorectal cancer were retrospectively enrolled. Whole-liver maps of original radiomics features were generated. A representative feature was selected for each feature class based on the visualization of example lesions from five patients. These maps and the conventional CT image data were viewed and evaluated by four readers in terms of liver parenchyma, number of lesions, visual contrast of lesions and diagnostic confidence. T-tests and chi²-tests were performed with a significance cut off of p<0.05 to compare the feature maps with SCRT, and the data were visualized as boxplots. Results: Regarding the number of lesions detected, SCTR showed superior performance compared to radiomics maps. However, the feature map for firstorder RootMeanSquared was ranked superior in terms of very high visual contrast in 57.4% of cases, compared to 41.0% in standard reconstructions (p < 0.001). All other radiomics maps ranked significantly lower in visual contrast when compared to SCTR. For diagnostic confidence, firstorder RootMeanSquared reached very high ratings in 47.9% of cases, compared to 62.8% for SCTR (p < 0.001). The conventional CT images showed superior results in all categories for the other features investigated. Conclusion: The application of firstorder RootMeanSquared feature maps may help visualize faintly demarcated liver lesions by increasing visual contrast. However, reading of SCTR remains necessary for diagnostic confidence. [ABSTRACT FROM AUTHOR]

BackgroundIn recent years, the incidence of patients with colorectal neuroendocrine neoplasms (CRNENs) has been continuously increasing. When diagnosed, most patients have distant metastases. Liver metastasis (LM) is the most common type of distant metastasis, and the prognosis is poor once it occurs. However, there is still a lack of large studies on the risk and prognosis of LM in CRNENs. This study aims to identify factors related to LM and prognosis and to develop a predictive model accordingly.MethodsIn this study, the Surveillance, Epidemiology, and End Results (SEER) database was used to collect clinical data from patients with CRNENs. The logistic regression analyses were conducted to identify factors associated with LM in patients with CRNENs. The patients with LM formed the prognostic cohort, and Cox regression analyses were performed to evaluate prognostic factors in patients with liver metastasis of colorectal neuroendocrine neoplasms (LM-CRNENs). Predictive and prognostic nomogram models were constructed based on the multivariate logistic and Cox analysis results. Finally, the capabilities of the nomogram models were verified through model assessment metrics, including the receiver operating characteristic (ROC) curves, calibration curve, and decision curve analysis (DCA) curve.ResultsThis study ultimately encompassed a total of 10,260 patients with CRNENs. Among these patients, 501 cases developed LM. The result of multivariate logistic regression analyses indicated that histologic type, tumor grade, T stage, N stage, lung metastasis, bone metastasis, and tumor size were independent predictive factors for LM in patients with CRNENs (p < 0.05). Multivariate Cox regression analyses indicated that age, primary tumor site, histologic type, tumor grade, N stage, tumor size, chemotherapy, and surgery were independent prognostic factors (p < 0.05) for patients with LM-CRNENs. The predictive and prognostic nomogram models were established based on the independent factors of logistic and Cox analyses. The nomogram models can provide higher accuracy and efficacy in predicting the probability of LM in patients with CRNENs and the prognosis of patients with LM.ConclusionThe factors associated with the occurrence of LM in CRNENs were identified. On the other hand, the relevant prognostic factors for patients with LM-CRNENs were also demonstrated. The nomogram models, based on independent factors, demonstrate greater efficiency and accuracy, promising to provide clinical interventions and decision-making support for patients.

BackgroundCurrent studies on the establishment of prognostic model for renal cell carcinoma (RCC) with liver metastases (LM) were scarce. This study aimed to develop nomograms to predict the prognosis of RCC with LM.MethodsPatients diagnosed with RCC between 2010 and 2021 from the Surveillance, Epidemiology, and End Results (SEER) database were selected. The eXtreme Gradient Boosting (XGBoost) and Random Forest (RF) machine learning algorithms were used to screen for the most influential factors affecting prognosis, and the Venn diagram method was employed for further refinement. Subsequently, a nomogram related to brain metastases was constructed. The performance of the nomograms was evaluated through receiver operating characteristics (ROC) curves, calibration plots, C-index, time-dependent C-index, and decision curve analysis (DCA). Kaplan–Meier (K-M) survival curves were used to provide additional verification of the clinical efficacy of the nomogram.ResultsThis research comprised 2,395 RCC patients with LM. The Venn diagram demonstrated that age, histological type, grade, AJCC T stage, AJCC N stage, surgery, chemotherapy, marital status, and lung metastasis were highly relevant variables to patients with LM. The AUC, C-index, calibration curves, and DCA curves showed excellent performance of the nomogram. Additionally, the prognostic nomogram accurately classified RCC with LM patients into low- and high-risk groups for mortality.ConclusionThis study developed a novel nomogram to predict the prognostic factors of RCC with LM, providing a valuable reference for making accurate clinical decisions.

IntroductionSurgical resection is gold standard for treatment of liver metastasis, locally ablative techniques including computer tomography (CT)-guided interstitial high-dose-rate (HDR) brachytherapy (CT-BRT) and stereotactic body radiotherapy (SBRT) have gained prominence as alternatives, offering comparable outcomes in selected patients. We aim to compare CT-BRT and SBRT - based on dosimetric analysis.Material and methodsPatients who underwent CT-BRT for oligometastatic, ≤4cm liver metastases between 2018 and 2024 were eligible. SBRT plans for Halcyon (SBRTh) and TrueBeam (SBRTtb) were prepared virtually. In the CT-BRT group CTV was equal to PTV, for SBRTh and SBRTtb planning, a 5 mm margin was applied to CTV to create PTV. Dose calculation was carried out with the TG-43 algorithm for CT-BRT and Anisotropic Analytical Algorithm for SBRTh and SBRTtb group. Descriptive statistics were used to compare the data. The Wilcoxon pairwise order test was utilized to compare dependent groups.ResultsCT-BRT resulted in a more favorable dose distribution within PTVs for Dmean, D50, and D90, while SBRT showed better results for D98 and V27.5Gy. No significant differences were observed for V25Gy between CT-BRT and SBRTtb, but SBRTh favored over CT-BRT. For OARs, CT-BRT plans showed better values for V5, V10, and V11.6Gy in the uninvolved liver volume. There were no significant differences in dose distribution for the duodenum, bowel, and heart. SBRT modalities performed better in the kidney. CT-BRT had improved dose distribution in the esophagus, great vessels, ribs, skin, spinal cord, and stomach compared to SBRT.ConclusionsCT-BRT could be a viable alternative to SBRT for certain patients with liver malignancies.

BackgroundThe liver is a frequent location of metastatic disease in various malignant tumor entities. Computed tomography (CT) is the most frequently employed modality for initial diagnosis. However, liver metastases may only be delineated vaguely on CT. Calculating radiomics features in feature maps can unravel textures not visible to the human eye on a standard CT reconstruction (SCTR). This study aimed to investigate the comparative diagnostic accuracy of radiomics feature maps and SCTR for liver metastases.Materials and methodsForty-seven patients with hepatic metastatic colorectal cancer were retrospectively enrolled. Whole-liver maps of original radiomics features were generated. A representative feature was selected for each feature class based on the visualization of example lesions from five patients. These maps and the conventional CT image data were viewed and evaluated by four readers in terms of liver parenchyma, number of lesions, visual contrast of lesions and diagnostic confidence. T-tests and chi²-tests were performed with a significance cut off of p

Purpose: To explore the efficacy and safety of FOLFOXIRI plus cetuximab regimen as conversion therapy for patients with unresectable RAS/BRAF wildtype colorectal liver-limited metastases (CLM). Patients and methods: This was a dual-center, phase II trial with the rate of no evidence of disease (NED) achieved as the primary endpoint. All enrolled patients with initially unresectable left-sided RAS/BRAF wild-type colorectal liver-limited metastases received a modified FOLFOXIRI plus cetuximab regimen as conversion therapy. Results: Between October 2019 and October 2021, fifteen patients were enrolled. Nine patients (60%) achieved NED. The overall response rate (ORR) was 92.9%, and the disease control rate (DCR) was 100%. The median relapsefree survival (RFS) was 9 (95% CI: 0-20.7) months. The median progression-free survival (PFS) was 13.0 months (95% CI: 5.7-20.5), and the median overall survival (OS) was not reached. The most frequently occurring grade 3-4 adverse events were neutropenia (20%), peripheral neurotoxicity (13.3%), diarrhea (6.7%), and rash acneiform (6.7%). Conclusion: The FOLFOXIRI plus cetuximab regimen displayed tolerable toxicity and promising anti-tumor activity in terms of the rate of NED achieved and response rate in patients with initially unresectable left-sided RAS/BRAF wildtype CLM. This regimen merits further investigation. [ABSTRACT FROM AUTHOR]

Introduction: The phase 3 CLEAR study demonstrated that lenvatinib plus pembrolizumab significantly improved efficacy versus sunitinib as first-line treatment for patients with advanced renal cell carcinoma (RCC). Prognostic features including presence and/or site of baseline metastases, prior nephrectomy, and sarcomatoid features have been associated with disease and treatment success. This subsequent analysis explores outcomes in patients with or without specific prognostic features. Methods: In CLEAR, patients with clear cell RCC were randomly assigned (1:1:1) to receive either lenvatinib (20 mg/day) plus pembrolizumab (200 mg every 3 weeks), lenvatinib (18 mg/day) plus everolimus (5 mg/day), or sunitinib alone (50 mg/day, 4 weeks on, 2 weeks off). In this report, progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) were all assessed in the lenvatinib-plus-pembrolizumab and the sunitinib arms, based on baseline features: lung metastases, bone metastases, liver metastases, prior nephrectomy, and sarcomatoid histology. Results: In all the assessed subgroups, median PFS was longer with lenvatinib-plus-pembrolizumab than with sunitinib treatment, notably among patients with baseline bone metastases (HR 0.33, 95% CI 0.21–0.52) and patients with sarcomatoid features (HR 0.39, 95% CI 0.18–0.84). Median OS favored lenvatinib plus pembrolizumab over sunitinib irrespective of metastatic lesions at baseline, prior nephrectomy, and sarcomatoid features. Of interest, among patients with baseline bone metastases the HR for survival was 0.50 (95% CI 0.30–0.83) and among patients with sarcomatoid features the HR for survival was 0.91 (95% CI 0.32–2.58); though for many groups, median OS was not reached. ORR also favored lenvatinib plus pembrolizumab over sunitinib across all subgroups; similarly, complete responses also followed this pattern. Conclusion: Efficacy outcomes improved following treatment with lenvatinib-plus-pembrolizumab versus sunitinib in patients with RCC—irrespective of the presence or absence of baseline lung metastases, baseline bone metastases, baseline liver metastases, prior nephrectomy, or sarcomatoid features. These findings corroborate those of the primary CLEAR study analysis in the overall population and support lenvatinib plus pembrolizumab as a standard of care in 1L treatment for patients with advanced RCC. [ABSTRACT FROM AUTHOR]

PurposeTo explore the efficacy and safety of FOLFOXIRI plus cetuximab regimen as conversion therapy for patients with unresectable RAS/BRAF wild-type colorectal liver-limited metastases (CLM).Patients and methodsThis was a dual-center, phase II trial with the rate of no evidence of disease (NED) achieved as the primary endpoint. All enrolled patients with initially unresectable left-sided RAS/BRAF wild-type colorectal liver-limited metastases received a modified FOLFOXIRI plus cetuximab regimen as conversion therapy.ResultsBetween October 2019 and October 2021, fifteen patients were enrolled. Nine patients (60%) achieved NED. The overall response rate (ORR) was 92.9%, and the disease control rate (DCR) was 100%. The median relapse‐free survival (RFS) was 9 (95% CI: 0–20.7) months. The median progression-free survival (PFS) was 13.0 months (95% CI: 5.7-20.5), and the median overall survival (OS) was not reached. The most frequently occurring grade 3-4 adverse events were neutropenia (20%), peripheral neurotoxicity (13.3%), diarrhea (6.7%), and rash acneiform (6.7%).ConclusionThe FOLFOXIRI plus cetuximab regimen displayed tolerable toxicity and promising anti-tumor activity in terms of the rate of NED achieved and response rate in patients with initially unresectable left-sided RAS/BRAF wild-type CLM. This regimen merits further investigation.

Liver is the most common site of colorectal cancer (CRC) metastases. Treatment of CRC liver metastases (CRLM) includes different strategies, prevalently based on the clinical and oncological intent. Valid approaches in liver-limited or liver-prevalent disease include surgery, percutaneous ablative procedures (radiofrequency ablation, microwave ablation), intra-arterial perfusional techniques (chemo-embolization, radio-embolization) as well as stereotactic radiotherapy. Systemic treatments, including chemotherapy, immunotherapy and other biological agents, are the only options for patients with no chance of locoregional approaches. The use of chemotherapy in other settings, such as neoadjuvant, adjuvant or conversion therapy of CRLM, is commonly accepted in the clinical practice, although data from several clinical trials have been mostly inconclusive. The optimal integration of all these strategies, when applicable and clinically indicated, should be ever considered in patients affected by CRLM based on clinical evidence and multidisciplinary experience. Here we revised in detail all the possible therapeutic approaches of CRLM focusing on the current evidences, the studies still in progress and the often contradictory data. [ABSTRACT FROM AUTHOR]

Background: Gastric cancer is a common cancer worldwide and is responsible for over one million new cases in 2020 and an estimated 769,000 deaths, ranking fifth for incidence and fourth for mortality globally. Incidence rates are highest in Eastern Asia and Eastern Europe. Gastric cancer is highly heterogeneous and progresses rapidly. The prognosis of gastric cancer with liver metastases is poor, and clinical treatment remains challenging. Human epidermal growth factor receptor 2 (HER2) positivity is correlated to a bad prognosis for gastric cancer. Trastuzumab combined with systemic chemotherapy is the preferred treatment for HER2-positive advanced gastric cancer. However, intravenous chemotherapy has severe systemic toxicity, which reduces the local drug concentration and tumor uptake rate, and the effect is unsatisfactory. Case summary: We reported a 66-year-old patient with HER2-positive advanced gastric cancer with jaundice due to multiple liver metastases, after 6 cycles of trastuzumab combined with hepatic arterial infusion chemotherapy (HAIC), the tumor retracted significantly, the jaundice subsided, and the patient recovered well. The patient achieved disease control with an intensive regimen followed by less toxic maintenance therapy. Trastuzumab combined with capecitabine maintenance therapy followed up for more than 16 months. Conclusion: HAIC plus trastuzumab may be a tolerable treatment option for patients with severe liver metastases from HER2-positive gastric cancer to achieve local control and prolong survival. [ABSTRACT FROM AUTHOR]

BackgroundGastric cancer is a common cancer worldwide and is responsible for over one million new cases in 2020 and an estimated 769,000 deaths, ranking fifth for incidence and fourth for mortality globally. Incidence rates are highest in Eastern Asia and Eastern Europe. Gastric cancer is highly heterogeneous and progresses rapidly. The prognosis of gastric cancer with liver metastases is poor, and clinical treatment remains challenging. Human epidermal growth factor receptor 2 (HER2) positivity is correlated to a bad prognosis for gastric cancer. Trastuzumab combined with systemic chemotherapy is the preferred treatment for HER2-positive advanced gastric cancer. However, intravenous chemotherapy has severe systemic toxicity, which reduces the local drug concentration and tumor uptake rate, and the effect is unsatisfactory.Case summaryWe reported a 66-year-old patient with HER2-positive advanced gastric cancer with jaundice due to multiple liver metastases, after 6 cycles of trastuzumab combined with hepatic arterial infusion chemotherapy (HAIC), the tumor retracted significantly, the jaundice subsided, and the patient recovered well. The patient achieved disease control with an intensive regimen followed by less toxic maintenance therapy. Trastuzumab combined with capecitabine maintenance therapy followed up for more than 16 months.ConclusionHAIC plus trastuzumab may be a tolerable treatment option for patients with severe liver metastases from HER2-positive gastric cancer to achieve local control and prolong survival.

Introduction: Sarcopenia is defined as a decline in muscle function as well as muscle mass. Sarcopenia itself and sarcopenic obesity, defined as sarcopenia in obese patients, have been used as surrogates for a worse prognosis in colorectal cancer. This review aims to determine if there is evidence for sarcopenia as a prognostic parameter in colorectal liver metastases (CRLM). Methods: PubMed, Embase, Cochrane Central, Web of Science, SCOPUS, and CINAHL databases were searched for articles that were selected in accordance with the PRISMA guidelines. The primary outcomes were overall survival (OS) and disease-free survival (DFS). A random effects meta-analysis was conducted. Results: After eliminating duplicates and screening abstracts (n = 111), 949 studies were screened, and 33 publications met the inclusion criteria. Of them, 15 were selected after close paper review, and 10 were incorporated into the meta-analysis, which comprised 825 patients. No significant influence of sarcopenia for OS (odds ratio (OR), 2.802 (95% confidence interval (CI), 1.094-1.11); p = 0.4) or DFS (OR, 1.203 (95% CI, 1.162-1.208); p = 0.5) was found, although a trend was defined toward sarcopenia. Sarcopenia significantly influenced postoperative complication rates (OR, 7.905 (95% CI, 1.876-3.32); p = 0.001) in two studies where data were available. Conclusion: Existing evidence on the influence of sarcopenia on postoperative OS as well as DFS in patients undergoing resection for CRLM exists. We were not able to confirm that sarcopenic patients have a significantly worse OS and DFS in our analysis, although a trend toward this hypothesis was visible. Sarcopenia seems to influence complication rates but prospective studies are needed. [ABSTRACT FROM AUTHOR]

Introduction: The phase 3 CLEAR study demonstrated that lenvatinib plus pembrolizumab significantly improved efficacy versus sunitinib as first-line treatment for patients with advanced renal cell carcinoma (RCC). Prognostic features including presence and/or site of baseline metastases, prior nephrectomy, and sarcomatoid features have been associated with disease and treatment success. This subsequent analysis explores outcomes in patients with or without specific prognostic features. Methods: In CLEAR, patients with clear cell RCC were randomly assigned (1:1:1) to receive either lenvatinib (20 mg/day) plus pembrolizumab (200 mg every 3 weeks), lenvatinib (18 mg/day) plus everolimus (5 mg/day), or sunitinib alone (50 mg/day, 4 weeks on, 2 weeks off). In this report, progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) were all assessed in the lenvatinib-plus-pembrolizumab and the sunitinib arms, based on baseline features: lung metastases, bone metastases, liver metastases, prior nephrectomy, and sarcomatoid histology. Results: In all the assessed subgroups, median PFS was longer with lenvatinib-plus-pembrolizumab than with sunitinib treatment, notably among patients with baseline bone metastases (HR 0.33, 95% CI 0.21–0.52) and patients with sarcomatoid features (HR 0.39, 95% CI 0.18–0.84). Median OS favored lenvatinib plus pembrolizumab over sunitinib irrespective of metastatic lesions at baseline, prior nephrectomy, and sarcomatoid features. Of interest, among patients with baseline bone metastases the HR for survival was 0.50 (95% CI 0.30–0.83) and among patients with sarcomatoid features the HR for survival was 0.91 (95% CI 0.32–2.58); though for many groups, median OS was not reached. ORR also favored lenvatinib plus pembrolizumab over sunitinib across all subgroups; similarly, complete responses also followed this pattern. Conclusion: Efficacy outcomes improved following treatment with lenvatinib-plus-pembrolizumab versus sunitinib in patients with RCC—irrespective of the presence or absence of baseline lung metastases, baseline bone metastases, baseline liver metastases, prior nephrectomy, or sarcomatoid features. These findings corroborate those of the primary CLEAR study analysis in the overall population and support lenvatinib plus pembrolizumab as a standard of care in 1L treatment for patients with advanced RCC. [ABSTRACT FROM AUTHOR]

Background: As the most common gastrointestinal malignancy worldwide, liver metastases occur in half colorectal cancer (CRC) patients. Early detection can help treat them early and reduce mortality in patients with colorectal cancer liver metastases (CRLM). Finding useful biomarkers for CRLM is thus essential. Methods: The TCGA and GEO databases were used to download the expression profiles and clinical data of the patients. Differential analysis screened for genes associated with CRLM, and univariate Cox regression analysis identified genes associated with prognosis. The least absolute shrinkage and selection operator (LASSO) method further preferred genes to construct a prognostic signature. Kaplan-Meier survival curves were used to show patients' overall survival (OS). Receiver operating characteristic (ROC) curves showed the accuracy of the model. Risk scores and clinical characteristics of patients were included in multivariate Cox regression analysis to identify independent risk factors, and a nomogram was constructed. The proportion of immune cells and infiltration were assessed using the 'CIBERSORT' package and the 'ESTIMATE' package. Results: We constructed a signature consisting of seven CRLM-associated genes, and signature-based risk scores have great potential in estimating the prognosis of CRC patients. Moreover, the poor response to immunotherapy in high-risk patients might contribute to the poor prognosis of individuals. Furthermore, we found that overexpression of Hepcidin antimicrobial peptide (HAMP), the only gene highly expressed in CRC and liver metastatic tissues, promoted CRC development and that it was associated with tumor mutation burden (TMB), DNA mismatch repair (MMR) genes, and microsatellite instability (MSI) in various tumors. Finally, we found that in CRC patients, low expression of HAMP also represented a better immunotherapeutic outcome, reflecting the critical role of HAMP in guiding immunotherapy. Conclusion: We identified a prognostic signature containing 7 CRLMassociated genes, and the signature was specified as an independent predictor and a nomogram containing the risk score was built accordingly. In addition, the derived gene HAMP could help guide the exploration of profitable immunotherapeutic strategies. [ABSTRACT FROM AUTHOR]

Background: The risk and prognosis of young breast cancer (YBC) with liver metastases (YBCLM) remain unclear. Thus, this study aimed to determine the risk and prognostic factors in these patients and construct predictive nomogram models. Methods: This population-based retrospective study was conducted using data of YBCLM patients from the Surveillance, Epidemiology, and End Results database between 2010 and 2019. Multivariate logistic and Cox regression analyses were used to identify independent risk and prognostic factors, which were used to construct the diagnostic and prognostic nomograms. The concordance index (C-index), calibration plot, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA) were used to assess the performances of the established nomogram models. Propensity score matching (PSM) analysis was used to balance the baseline characteristics between the YBCLM patients and non-young patients with BCLM when comparing overall survival (OS) and cancer-specific survival (CSS). Results: A total of 18,275 YBC were identified, of whom 400 had LM. T stage, N stage, molecular subtypes, and bone, lung, and brain metastases were independent risk factors for LM developing in YBC. The established diagnostic nomogram showed that bone metastases contributed the most risk of LM developing, with a C-index of 0.895 (95% confidence interval 0.877-0.913) for this nomogram model. YBCLM had better survival than non-young patients with BCLM in unmatched and matched cohorts after propensity score matching analysis. The multivariate Cox analysis demonstrated that molecular subtypes, surgery and bone, lung, and brain metastases were independently associated with OS and CSS, chemotherapy was an independent prognostic factor for OS, and marital status and T stage were independent prognostic factors for CSS. The Cindices for the OS- and CSS-specific nomograms were 0.728 (0.69-0.766) and 0.74 (0.696-0.778), respectively. The ROC analysis indicated that these models had excellent discriminatory power. The calibration curve also showed that the observed results were consistent with the predicted results. DCA showed that the developed nomogram models would be effective in clinical practice. Conclusion: The present study determined the risk and prognostic factors of YBCLM and further developed nomograms that can be used to effectively identify high-risk patients and predict survival outcomes. [ABSTRACT FROM AUTHOR]

Adrenocortical carcinoma (ACC) is a rare, heterogeneous, and aggressive malignancy with a generally poor prognosis. Surgical resection is the optimal treatment plan. After surgery, both mitotane treatment or the etoposidedoxorubicin-cisplatin (EDP) protocol plus mitotane chemotherapy have a certain effect, but there is still an extremely high possibility of recurrence and metastasis. The liver is one of the most common metastatic targets. Therefore, techniques such as transcatheter arterial chemoembolization (TACE) and microwave ablation (MWA) for liver tumors can be attempted in a specific group of patients. We present the case of a 44-year-old female patient with primary ACC, who was diagnosed with liver metastasis 6 years after resection. During mitotane treatment, we performed four courses of TACE and two MWA procedures in accordance with her clinical condition. The patient has maintained the partial response status and has currently returned to normal life to date. This case illustrates the value of the practical application of mitotane plus TACE and MWA treatment. [ABSTRACT FROM AUTHOR]

The liver is the most common and lethal metastatic site in patients with extensive-stage small-cell lung cancer (ES-SCLC), and median survival with current standard treatment is only 9-10 months from diagnosis. Clinical observations show that a complete response (CR) is extremely rare in ES-SCLC patients with liver metastasis. Moreover, to the best of our knowledge, complete regression of liver metastasis induced by the abscopal effect, boosted primarily by permanent radioactive iodine-125 seeds implantation (PRISI), combined with a low-dose metronomic temozolomide (TMZ) regimen, has not been recorded. Here, we present the case of a 54-year-old male patient who developed multiple liver metastases from ES-SCLC after multiple lines of chemotherapy. The patient was given partial PRISI therapy (two out of six tumor lesions; 38 iodine-125 seeds in one dorsal lesion and 26 seeds in one ventral lesion), which was combined with TMZ metronomic chemotherapy (50 mg/m2/day, days 1-21, every 28 days). The abscopal effect was observed for 1 month after PRISI treatment. After about 1 year, all the liver metastases had completely disappeared, and the patient experienced no relapse. The patient eventually died of malnutrition caused by a non-tumor intestinal obstruction and had an overall survival of 58.5 months after diagnosis. PRISI combined with TMZ metronomic chemotherapy might be considered a potential therapy to trigger the abscopal effect in patients with liver metastases. [ABSTRACT FROM AUTHOR]

IntroductionSarcopenia is defined as a decline in muscle function as well as muscle mass. Sarcopenia itself and sarcopenic obesity, defined as sarcopenia in obese patients, have been used as surrogates for a worse prognosis in colorectal cancer. This review aims to determine if there is evidence for sarcopenia as a prognostic parameter in colorectal liver metastases (CRLM).MethodsPubMed, Embase, Cochrane Central, Web of Science, SCOPUS, and CINAHL databases were searched for articles that were selected in accordance with the PRISMA guidelines. The primary outcomes were overall survival (OS) and disease-free survival (DFS). A random effects meta-analysis was conducted.ResultsAfter eliminating duplicates and screening abstracts (n = 111), 949 studies were screened, and 33 publications met the inclusion criteria. Of them, 15 were selected after close paper review, and 10 were incorporated into the meta-analysis, which comprised 825 patients. No significant influence of sarcopenia for OS (odds ratio (OR), 2.802 (95% confidence interval (CI), 1.094–1.11); p = 0.4) or DFS (OR, 1.203 (95% CI, 1.162–1.208); p = 0.5) was found, although a trend was defined toward sarcopenia. Sarcopenia significantly influenced postoperative complication rates (OR, 7.905 (95% CI, 1.876–3.32); p = 0.001) in two studies where data were available.ConclusionExisting evidence on the influence of sarcopenia on postoperative OS as well as DFS in patients undergoing resection for CRLM exists. We were not able to confirm that sarcopenic patients have a significantly worse OS and DFS in our analysis, although a trend toward this hypothesis was visible. Sarcopenia seems to influence complication rates but prospective studies are needed.

IntroductionThe phase 3 CLEAR study demonstrated that lenvatinib plus pembrolizumab significantly improved efficacy versus sunitinib as first-line treatment for patients with advanced renal cell carcinoma (RCC). Prognostic features including presence and/or site of baseline metastases, prior nephrectomy, and sarcomatoid features have been associated with disease and treatment success. This subsequent analysis explores outcomes in patients with or without specific prognostic features.MethodsIn CLEAR, patients with clear cell RCC were randomly assigned (1:1:1) to receive either lenvatinib (20 mg/day) plus pembrolizumab (200 mg every 3 weeks), lenvatinib (18 mg/day) plus everolimus (5 mg/day), or sunitinib alone (50 mg/day, 4 weeks on, 2 weeks off). In this report, progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) were all assessed in the lenvatinib-plus-pembrolizumab and the sunitinib arms, based on baseline features: lung metastases, bone metastases, liver metastases, prior nephrectomy, and sarcomatoid histology.ResultsIn all the assessed subgroups, median PFS was longer with lenvatinib-plus-pembrolizumab than with sunitinib treatment, notably among patients with baseline bone metastases (HR 0.33, 95% CI 0.21–0.52) and patients with sarcomatoid features (HR 0.39, 95% CI 0.18–0.84). Median OS favored lenvatinib plus pembrolizumab over sunitinib irrespective of metastatic lesions at baseline, prior nephrectomy, and sarcomatoid features. Of interest, among patients with baseline bone metastases the HR for survival was 0.50 (95% CI 0.30–0.83) and among patients with sarcomatoid features the HR for survival was 0.91 (95% CI 0.32–2.58); though for many groups, median OS was not reached. ORR also favored lenvatinib plus pembrolizumab over sunitinib across all subgroups; similarly, complete responses also followed this pattern.ConclusionEfficacy outcomes improved following treatment with lenvatinib-plus-pembrolizumab versus sunitinib in patients with RCC—irrespective of the presence or absence of baseline lung metastases, baseline bone metastases, baseline liver metastases, prior nephrectomy, or sarcomatoid features. These findings corroborate those of the primary CLEAR study analysis in the overall population and support lenvatinib plus pembrolizumab as a standard of care in 1L treatment for patients with advanced RCC.Clinical trial registrationClinicalTrials.gov, identifier NCT02811861

Immune checkpoint inhibitors have reshaped the prognostic of several tumor types, including metastatic colorectal tumors with microsatellite instability (MSI). However, 90-95% of metastatic colorectal tumors are microsatellite stable (MSS) in which immunotherapy has failed to demonstrate meaningful clinical results. MSS colorectal tumors are considered immune-cold tumors. Several factors have been proposed to account for this lack of response to immune checkpoint blockade including low levels of tumor infiltrating lymphocytes, low tumor mutational burden, a high rate of WNT/b-catenin pathway mutations, and liver metastases which have been associated with immunosuppression. However, studies with novel combinations based on immune checkpoint inhibitors are showing promising activity in MSS colorectal cancer. Here, we review the underlying biological facts that preclude immunotherapy activity, and detail the different immune checkpoint inhibitor combinations evaluated, along with novel immune-based therapies, to overcome innate mechanisms of resistance in MSS colorectal cancer. [ABSTRACT FROM AUTHOR]

The liver is the most common and lethal metastatic site in patients with extensive-stage small-cell lung cancer (ES-SCLC), and median survival with current standard treatment is only 9–10 months from diagnosis. Clinical observations show that a complete response (CR) is extremely rare in ES-SCLC patients with liver metastasis. Moreover, to the best of our knowledge, complete regression of liver metastasis induced by the abscopal effect, boosted primarily by permanent radioactive iodine-125 seeds implantation (PRISI), combined with a low-dose metronomic temozolomide (TMZ) regimen, has not been recorded. Here, we present the case of a 54-year-old male patient who developed multiple liver metastases from ES-SCLC after multiple lines of chemotherapy. The patient was given partial PRISI therapy (two out of six tumor lesions; 38 iodine-125 seeds in one dorsal lesion and 26 seeds in one ventral lesion), which was combined with TMZ metronomic chemotherapy (50 mg/m2/day, days 1–21, every 28 days). The abscopal effect was observed for 1 month after PRISI treatment. After about 1 year, all the liver metastases had completely disappeared, and the patient experienced no relapse. The patient eventually died of malnutrition caused by a non-tumor intestinal obstruction and had an overall survival of 58.5 months after diagnosis. PRISI combined with TMZ metronomic chemotherapy might be considered a potential therapy to trigger the abscopal effect in patients with liver metastases.

ObjectivesLimited efforts have been made to evaluate the effect of multimodal chemotherapy on the survival of gastric cancer patients with liver metastases (LMGC). This study aimed to identify prognostic factors in LMGC patients and the superiority of multimodal chemotherapy with respect to overall survival (OS) in these patients.MethodsWe conducted a retrospective cohort study of 1298 patients with M1 stage disease between January 2012 and December 2020. The effects of clinicopathological variables and preoperative chemotherapy (PECT), postoperative chemotherapy (POCT), and palliative chemotherapy on survival in patients with liver metastases (LM group) and non-liver metastases (non-LM group) were compared.ResultsOf the 1298 patients analysed, 546 (42.06%) were in the LM group and 752 (57.94%) were in the non-LM group. The median (interquartile range) age was 60 (51–66) years. The 1-year, 3-year and 5-year overall survival (OS) rates in the LM group were 29.3%, 13.9%, and 9.2%, respectively, and those in the non-LM group were. 38.2%, 17.4%, and 10.0%, respectively (P < 0.05, > 0.05, and > 0.05, respectively.) The Cox proportional hazards model revealed that palliative chemotherapy was a significant independent prognostic factor in both the LM and non-LM groups. Age ≥55 years, N stage, and Lauren classification were also independent predictors of OS in the LM group (P < 0.05). Palliative chemotherapy and POCT were associated with improved OS compared with PECT in the LM group (26.3% vs. 36.4% vs. 25.0%, P < 0.001).ConclusionLMGC patients had a worse prognosis than non- LMGC. Number of metastatic sites more than 1, liver and other metastatic sites, no CT treatment and HER2-negative had a poor prognosis. LMGC patient may benefit more from palliative chemotherapy and POCT than from PECT. Further well-designed, prospective studies are needed to validate these findings.

Immune checkpoint inhibitors have reshaped the prognostic of several tumor types, including metastatic colorectal tumors with microsatellite instability (MSI). However, 90-95% of metastatic colorectal tumors are microsatellite stable (MSS) in which immunotherapy has failed to demonstrate meaningful clinical results. MSS colorectal tumors are considered immune-cold tumors. Several factors have been proposed to account for this lack of response to immune checkpoint blockade including low levels of tumor infiltrating lymphocytes, low tumor mutational burden, a high rate of WNT/β-catenin pathway mutations, and liver metastases which have been associated with immunosuppression. However, studies with novel combinations based on immune checkpoint inhibitors are showing promising activity in MSS colorectal cancer. Here, we review the underlying biological facts that preclude immunotherapy activity, and detail the different immune checkpoint inhibitor combinations evaluated, along with novel immune-based therapies, to overcome innate mechanisms of resistance in MSS colorectal cancer.

Background: The predictive effects of liver metastases for immune-checkpoint inhibitors (ICIs) and the relationship between tumor mutational burden (TMB) and liver metastases (LM) remain unclear. Methods: A systematic review and meta-analysis were conducted to explore the heterogeneity of ICIs efficacy between patients with or without LM. A pan-cancer cohort of 1,661 patients who received ICIs was downloaded and analyzed to assess the association between TMB and LM. Results: Of 21053 studies identified in our search, eight single-arm studies and 24 randomized controlled trials were included. Overall, 17957 patients with advanced or metastatic cancers (4805 patients (26.8%) with LM and 13151 patients (73.2%) without LM) were enrolled. The pooled objective response rate (ORR) was 8.5% (95% CI 4%-13%) in the LM group versus 21% (95% CI 16%-21%) in the non-LM group. The pooled hazard ratio (HR) for death was 0.85 (95% CI 0.80-0.90) in the LM group treated with ICIs compared with the standard of care. In patients without LM who were treated with ICIs, the pooled HR for death was 0.78 (95% CI 0.73-0.82) compared with the standard of care. The difference in efficacy between patients with or without LM treated with ICIs was significant (p=0.04). Pan-cancer analysis revealed that the TMB-high rate was 10.8% in liver metastatic lesions versus 21.4% in other metastatic lesions (p=0.004). In addition, TMB was also significantly associated with OS as a binary cutoff (p=0.05) and was an independent prognostic variable (HR=0.98, P=0.047) as a continuous variable in patients with LM. Conclusions: In patients with LM, the efficacy of immunotherapy was attenuated, but TMB-high could predict better survival outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Stereotactic body radiotherapy (SBRT) is used to treat liver metastases with the intention of ablation. High local control rates were shown. Magnetic resonance imaging guided radiotherapy (MRgRT) provides the opportunity of a marker-less liver SBRT treatment due to the high soft tissue contrast. We report herein on one of the largest cohorts of patients treated with online MRgRT of liver metastases focusing on oncological outcome, toxicity, patient reported outcome measures (PROMs), quality of life. Material and methods: Patients treated for liver metastases with online MR-guided SBRT at a 1,5 T MR-Linac (Unity, Elekta, Crawley, UK) between March 2019 and December 2021 were included in this prospective study. UK SABR guidelines were used for organs at risk constraints. Oncological endpoints such as survival parameters (overall survival, progression-free survival) and local control as well as patient reported acceptance and quality of life data (EORTC QLQ-C30 questionnaire) were assessed. For toxicity scoring the Common Toxicity Criteria Version 5 were used. Results: A total of 51 patients with 74 metastases were treated with a median of five fractions. The median applied BED GTV D98 was 84,1 Gy. Median follow-up was 15 months. Local control of the irradiated liver metastasis after 12 months was 89,6%, local control of the liver was 40,3%. Overall survival (OS) after 12 months was 85.1%. Progression free survival (PFS) after 12 months was 22,4%. Local control of the irradiated liver lesion was 100% after three years when a BED ≥100 Gy was reached. The number of treated lesions did not impact local control neither of the treated or of the hepatic control. Patient acceptance of online MRgSBRT was high. There were no acute grade ≥ 3 toxicities. Quality of life data showed no significant difference comparing baseline and follow-up data. Conclusion: Online MR guided radiotherapy is a noninvasive, well-tolerated and effective treatment for liver metastases. Further prospective trials with the goal to define patients who actually benefit most from an online adaptive workflow are currently ongoing. [ABSTRACT FROM AUTHOR]

Purpose: In metastatic colorectal cancer (mCRC) patients (pts), treatment strategies integrating liver resection with induction chemotherapy offer better 5-year survival rates than chemotherapy alone. However, liver resection is a complex and costly procedure, and recurrence occurs in almost 2/3rds of pts, suggesting the need to identify those at higher risk. The aim of this work was to evaluate whether the integration of plasma metabolomics and lipidomics combined with the multiplex analysis of a large panel of plasma cytokines can be used to predict the risk of relapse and other patient outcomes after liver surgery, beyond or in combination with clinical morphovolumetric criteria. Experimental design: Peripheral blood metabolomics and lipidomics were performed by 600 MHz NMR spectroscopy on plasma from 30 unresectable mCRC pts treated with bevacizumab plus oxaliplatin-based regimens within the Obelics trial (NCT01718873) and subdivided into responder (R) and non-R (NR) according to 1-year disease-free survival (DFS): = 1-year (R, n = 12) and < 1-year (NR, n = 18). A large panel of cytokines, chemokines, and growth factors was evaluated on the same plasma using Luminex xMAP-based multiplex bead-based immunoassay technology. A multiple biomarkers model was built using a support vector machine (SVM) classifier. Results: Sparse partial least squares discriminant analysis (sPLS-DA) and loading plots obtained by analyzing metabolomics profiles of samples collected at the time of response evaluation when resectability was established showed significantly different levels of metabolites between the two groups. Two metabolites, 3-hydroxybutyrate and histidine, significantly predicted DFS and overall survival. Lipidomics analysis confirmed clear differences between the R and NR pts, indicating a statistically significant increase in lipids (cholesterol, triglycerides and phospholipids) in NR pts, reflecting a nonspecific inflammatory response. Indeed, a significant increase in proinflammatory cytokines was demonstrated in NR pts plasma. Finally, a multiple biomarkers model based on the combination of presurgery plasma levels of 3-hydroxybutyrate, cholesterol, phospholipids, triglycerides and IL-6 was able to correctly classify patients by their DFS with good accuracy. Conclusion: Overall, this exploratory study suggests the potential of these combined biomarker approaches to predict outcomes in mCRC patients who are candidates for liver metastasis resection after induction treatment for defining personalized management and treatment strategies. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study is to conduct a meta-analysis to assess the efficacy of yttrium-90 selective internal radiation therapy (SIRT) in treating patients with breast cancer with hepatic metastasis. Method: PubMed and The Cochrane Library were queried from establishment to January 2021. The following keywords were implemented: “breast”, “yttrium”, and “radioembolization”. The following variables and outcomes were collected: publication year, region, sample size, study design, presence of extrahepatic disease, tumor burden, infused radioactivity, breast cancer subtype, previous treatment, median survival time (MST), length of follow-up, adverse events, and radiographical response such as Response Evaluation Criteria in Solid Tumors (RECIST), modified RECIST (mRECIST), and Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST). Results: A total of 24 studies from 14 institutions were included in the present meta-analysis. On the basis of the data from 412 patients, post-embolization MST was 9.8 [95% confidence interval (CI): 9.0–11.6] months. Patients with additional extrahepatic metastasis had a poorer survival rate compared with those with localized hepatic metastasis only (MST: 5.3 vs. 15 months, p < 0.0001). Patients with <25% liver tumor burden exhibited more promising survival than those with >25% (MST: 10.5 vs. 6.8 months, p < 0.0139). On the basis of RECIST, mRECIST, and PERCIST criteria, tumor response rate was 36% (95% CI: 26%–47%), 49% (95% CI: 34%–65%), and 47% (95% CI: 17%–78%), respectively, whereas tumor control rate was 85% (95% CI: 76%–93%), 73% (95% CI: 59%–85%), and 97% (95% CI: 91%–100%), respectively. Conclusion: On the basis of the available published evidence, SIRT is feasible and effective in treating patients with breast cancer with liver metastasis. Patients with lower hepatic tumor burden and without extrahepatic metastasis demonstrated more survival benefit. Future randomized controlled trials are warranted. [ABSTRACT FROM AUTHOR]

PurposeIn metastatic colorectal cancer (mCRC) patients (pts), treatment strategies integrating liver resection with induction chemotherapy offer better 5-year survival rates than chemotherapy alone. However, liver resection is a complex and costly procedure, and recurrence occurs in almost 2/3rds of pts, suggesting the need to identify those at higher risk. The aim of this work was to evaluate whether the integration of plasma metabolomics and lipidomics combined with the multiplex analysis of a large panel of plasma cytokines can be used to predict the risk of relapse and other patient outcomes after liver surgery, beyond or in combination with clinical morphovolumetric criteria.Experimental designPeripheral blood metabolomics and lipidomics were performed by 600 MHz NMR spectroscopy on plasma from 30 unresectable mCRC pts treated with bevacizumab plus oxaliplatin-based regimens within the Obelics trial (NCT01718873) and subdivided into responder (R) and non-R (NR) according to 1-year disease-free survival (DFS): ≥ 1-year (R, n = 12) and < 1-year (NR, n = 18). A large panel of cytokines, chemokines, and growth factors was evaluated on the same plasma using Luminex xMAP-based multiplex bead-based immunoassay technology. A multiple biomarkers model was built using a support vector machine (SVM) classifier.ResultsSparse partial least squares discriminant analysis (sPLS-DA) and loading plots obtained by analyzing metabolomics profiles of samples collected at the time of response evaluation when resectability was established showed significantly different levels of metabolites between the two groups. Two metabolites, 3-hydroxybutyrate and histidine, significantly predicted DFS and overall survival. Lipidomics analysis confirmed clear differences between the R and NR pts, indicating a statistically significant increase in lipids (cholesterol, triglycerides and phospholipids) in NR pts, reflecting a nonspecific inflammatory response. Indeed, a significant increase in proinflammatory cytokines was demonstrated in NR pts plasma. Finally, a multiple biomarkers model based on the combination of presurgery plasma levels of 3-hydroxybutyrate, cholesterol, phospholipids, triglycerides and IL-6 was able to correctly classify patients by their DFS with good accuracy.ConclusionOverall, this exploratory study suggests the potential of these combined biomarker approaches to predict outcomes in mCRC patients who are candidates for liver metastasis resection after induction treatment for defining personalized management and treatment strategies.

IntroductionStereotactic body radiotherapy (SBRT) is used to treat liver metastases with the intention of ablation. High local control rates were shown. Magnetic resonance imaging guided radiotherapy (MRgRT) provides the opportunity of a marker-less liver SBRT treatment due to the high soft tissue contrast. We report herein on one of the largest cohorts of patients treated with online MRgRT of liver metastases focusing on oncological outcome, toxicity, patient reported outcome measures (PROMs), quality of life.Material and methodsPatients treated for liver metastases with online MR-guided SBRT at a 1,5 T MR-Linac (Unity, Elekta, Crawley, UK) between March 2019 and December 2021 were included in this prospective study. UK SABR guidelines were used for organs at risk constraints. Oncological endpoints such as survival parameters (overall survival, progression-free survival) and local control as well as patient reported acceptance and quality of life data (EORTC QLQ-C30 questionnaire) were assessed. For toxicity scoring the Common Toxicity Criteria Version 5 were used.ResultsA total of 51 patients with 74 metastases were treated with a median of five fractions. The median applied BED GTV D98 was 84,1 Gy. Median follow-up was 15 months. Local control of the irradiated liver metastasis after 12 months was 89,6%, local control of the liver was 40,3%. Overall survival (OS) after 12 months was 85.1%. Progression free survival (PFS) after 12 months was 22,4%. Local control of the irradiated liver lesion was 100% after three years when a BED ≥100 Gy was reached. The number of treated lesions did not impact local control neither of the treated or of the hepatic control. Patient acceptance of online MRgSBRT was high. There were no acute grade ≥ 3 toxicities. Quality of life data showed no significant difference comparing baseline and follow-up data.ConclusionOnline MR guided radiotherapy is a noninvasive, well-tolerated and effective treatment for liver metastases. Further prospective trials with the goal to define patients who actually benefit most from an online adaptive workflow are currently ongoing.

BackgroundTraditionally, synchronous liver resection (LR), cytoreductive surgery (CRS), and hyperthermic intraperitoneal chemotherapy for colorectal liver and peritoneal metastases have been contraindicated. Nowadays, clinical practice has promoted this aggressive treatment in selected cases. This study aimed to review surgical and survival results of an extensive surgical approach including CRS with hyperthermic intraperitoneal chemotherapy (HIPEC) and LR.MethodsPubMed, EMBASE, and Web of Science databases were matched to find the available literature on this topic. The search period was limited to 10 years (January 2010–January 2021). A threshold of case series of 10 patients or more was applied.ResultsIn the search period, out of 114 studies found about liver and peritoneal metastases from colorectal cancer, we found 18 papers matching the inclusion criteria. Higher morbidity and mortality were reported for patients who underwent such an extensive surgical approach when compared with patients who underwent only cytoreductive surgery and HIPEC. Also, survival rates seem worse in the former than in the latter.ConclusionThe role of combined surgical strategy in patients with synchronous liver and peritoneal metastases from colorectal cancer remains controversial. Survival rates and morbidity and mortality seem not in favor of this option. A more accurate selection of patients and more restrictive surgical indications could perhaps help improve results in this subgroup of patients with limited curative options.

Liver metastases (LM) occur in up to 90% either simultaneously with the diagnosis of the primary tumor or at a later time-point. While resection of colorectal LM and resection or transplantation of neuroendocrine LM is part of a standard therapy with a 5-year patient survival of up to 80%, resection of non-colorectal and non-neuroendocrine LM is still discussed controversially. The reason for it is the significantly lower survival benefit of all different tumor entities depending on the biological aggressiveness of the tumor. Randomized controlled trials are lacking. However, reviews of case series with ≥100 liver resections are available. They show a 5-year patient survival of up to 42% compared to only

Background: Liver metastasis is the most common type of lung cancer metastasis, and is a significant prognostic factor in lung cancer. However, the effect of liver metastases on the efficacy of immune checkpoint inhibitors (ICIs) remains inconsistent and controversial. The aim of this study was to explore the relationship between liver metastases and ICI efficacy in patients with advanced lung cancer based on data from randomized controlled trials (RCTs) and observational studies. Methods: PubMed, EMBASE, Cochrane Library databases, conference proceedings, as well as grey literature websites were searched for eligible studies without language restrict ion. Study quality was assessed using Cochrane tools and the Newcastle-Ottawa Quality Assessment Scale (NOS). Outcomes of interest were overall survival (OS) and progression-free survival (PFS). The difference in efficacy between patients with and without liver metastases was calculated by pooling ratios of hazard ratios (HR), as calculated using the deft approach. Results: A total of 16 RCTs and 14 observational trials were included. Analyses of RCTs revealed a survival benefit for ICI treatment (i.e., ICI monotherapy, ICI + Chemotherapy, dual ICI therapy and dual ICI + Chemotherapy) versus standard therapies among non-small cell lung cancer (NSCLC) patients with liver metastases (PFS HR, 0.77; 95%CI, 0.61-0.97; OS HR, 0.78; 95%CI, 0.68-0.90). NSCLC patients with liver metastases achieved less PFS benefit and comparable OS benefit from ICI treatment compared with those without liver metastases (ratios of PFS-HRs, 1.19; 95%CI, 1.02-1.39; P=0.029; Ratios of OS-HRs, 1.10; 95%CI, 0.94-1.29; P=0.24). For patients with small cell lung cancer (SCLC), ICI treatment achieved a marginal effect on patients with liver metastases as compared with standard therapies (OS HR, 0.94; 95%CI, 0.73-1.23). SCLC patients with liver metastases benefited less from ICI treatment than patients without liver metastases (ratio of OS-HRs, 1.22; 95%CI, 1.01-1.46; P=0.036). In real-world data analysis, liver metastasis could be used as an independent prognostic risk factor, increasing the risk of death by 21% in lung cancer patients receiving ICI treatment compared with those without liver metastases (OS HR, 1.21; 95%CI, 1.17-1.27; P<0.0001). Subgroup analysis confirmed that this association was not modified by race (Asian vs. Western) or number of treatment lines. Conclusions: The presence of liver metastases does not significantly influence the OS benefit of ICIs in patients with NSCLC. However, a small amount of data shows that liver metastasis restrains the magnitude of OS benefit in patients with SCLC. Liver metastasis has potential as an independent prognostic risk factor for lung cancer patients receiving ICI treatment in clinical practice. [ABSTRACT FROM AUTHOR]

Introduction: Parathyroid carcinoma (PC) is a very rare endocrine malignancy occurring in less than 1% of all cases of primary hyperparathyroidism (pHPT). The liver is the second most common target organ for distant metastases of PC, but no guidelines are available for the diagnosis and treatment of liver metastases. In this study, we attempted to summarize the characteristics of the diagnosis and treatment of liver metastases based on our patients and other cases reported in the literature. Materials and methods: The files of all patients diagnosed with PC with liver metastases summarized at our center between 2000 and 2022 were reviewed, and three datasets from Medline, Web of Science, and Embase were systematically searched to identify relevant articles. Results: Three patients with liver metastases from our center and 11 patients from the literature were included in the study. All patients had pHPT with borderline remission of hypercalcemia after each operation. A total of 71.4% of the patients' liver lesions were found by abdominal CT scans, while 35.7% were found by MRI, PET-CT, and fine-needle aspiration biopsy (FNAB), which were also helpful for diagnosis. Eight of nine patients (88.9%) who underwent surgery, radiofrequency ablation (RFA), or transcatheter arterial embolization (TAE) were alive, and only one postoperative patient died after a follow-up of 60 months. Conclusions: PC is a rare malignant tumor prone to recurrence and metastasis, and postoperative reviews should be carried out routinely. Abnormally elevated parathyroid hormone (PTH) and serum calcium can indicate recurrence or metastasis. Enhanced CT and MRI can provide valuable support for the diagnosis of liver metastases, but whether [18F]FDG-PET-CT, [18F]FCH-PETCT, or [11C]choline-PET-CT can be used as a diagnostic basis requires further study. Resection of liver metastases, segmental hepatectomy, or RFA can significantly improve patients' symptoms. [ABSTRACT FROM AUTHOR]

Background: The survival benefit of primary and metastatic resection for patients with colorectal cancer with liver metastasis (CRLM) has been observed, but methods for discriminating which individuals would benefit from surgery have been poorly defined. Herein, a predictive model was developed to stratify patients into sub-population based on their response to surgery. Methods: We assessed the survival benefits for adults diagnosed with colorectal liver metastasis by comparing patients with curative surgery vs. those without surgery. CRLM patients enrolled in the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2015 were identified for model construction. Other data including CRLM patients from our center were obtained for external validation. Calibration plots, the area under the curve (AUC), and decision curve analysis (DCA) were used to evaluate the performance of the nomogram compared with the tumor-node-metastasis (TNM) classification. The Kaplan-Meier analysis was performed to examine whether this model would distinguish patients who could benefit from surgery. Results: A total of 1,220 eligible patients were identified, and 881 (72.2%) underwent colorectal and liver resection. Cancer-specific survival (CSS) for the surgery group was significantly better than that for the no-surgery group (41 vs. 14 months, p < 0.001). Five factors were found associated with CSS and adopted to build the nomograms, i.e., age, T stage, N stage, neoadjuvant chemotherapy, and primary tumor position. The AUC of the CRLM nomogram showed a better performance in identifying patients who could obtain benefits in the surgical treatment, compared with TNM classification (training set, 0.826 [95% CI, 0.786-0.866] vs. 0.649 [95% CI, 0.598-0.701]; internal validation set, 0.820 [95% CI, 0.741-0.899] vs. 0.635 [95% CI, 0.539-0.731]; external validation set, 0.763 [95% CI, 0.691-0.836] vs. 0.626 [95% CI, 0.542-0.710]). The calibration curves revealed excellent agreement between the predicted and actual survival outcomes. The DCA showed that the nomogram exhibited more clinical benefits than the TNM staging system. The beneficial and surgery group survived longer significantly than the non-beneficial and surgery group (HR = 0.21, 95% CI, 0.17-0.27, p < 0.001), but no difference was observed between the non-beneficial and surgery and non-surgery groups (HR = 0.89, 95% CI, 0.71-1.13, p = 0.344). Conclusions: An accurate and easy-to-use CRLM nomogram has been developed and can be applied to identify optimal candidates for the resection of primary and metastatic lesions among CRLM patients. [ABSTRACT FROM AUTHOR]

Background: The purpose was to compare the efficacy and safety of hepatic arterial infusion (HAI) of oxaliplatin plus raltitrexed (TOMOX) to those of oxaliplatin plus 5-fluorouracil (FOLFOX) for unresectable colorectal cancer liver metastases (CRCLM). Methods: Patients with unresectable CRCLM were randomly assigned to receive HAI of TOMOX or FOLFOX. The primary end points were progression-free survival (PFS) measured from the date of randomisation until the date of disease progression and objective response rate (ORR). The secondary end points were overall survival (OS) measured from the date of randomisation until the date of death from any cause, disease control rate (DCR), and adverse events. Results: 113 patients were randomly assigned. With a median follow-up of 39.5 months, the PFS was 5.8 months [95% CI, 4.838-6.762]) and 4.6 months [95% CI, 3.419-5.781; P = 0.840], and the median OS was 17.6 months [95% CI, 13.828-21.372] and 13.1 months [95% CI, 11.215-14.985; P = 0.178] for the FOLFOX and TOMOX arm, respectively. The ORR were 26.1% vs 22.4% and DCR were 80.4% vs 71.4% in the FOLFOX and TOMOX arms. The most common severe adverse event was elevation of liver enzymes and pain, which did not differ in the two arms. Conclusion: HAI chemotherapy was effective for unresectable CRCLM. HAI of FOLFOX has similar efficacy to TOMOX, and HAI of TOMOX had shorter arterial infusion time. [ABSTRACT FROM AUTHOR]

Background: The specific efficacy of immunotherapy for patients with liver metastases of gastric cancer is unclear. This study set out to explore the treatment response and related prognostic factors for patients with liver metastases of gastric cancer treated with immunotherapy. Patients and methods: This retrospective cohort study included 135 patients with unresectable advanced gastric cancer. According to the presence of liver metastases and/or first-line treatment with immunotherapy, patients were divided into the following three groups: I-LM(-) group(patients without liver metastases treated with immunotherapy, n=66), I-LM(+) group(patients with liver metastases treated with immunotherapy, n=36), C-LM(+) group(patients with liver metastases treated with chemotherapy and/or target therapy, n=33). Cox regression analyses were used to identify factors associated with survival in all patients and the three groups, respectively. Results: For the patients with liver metastases treated with immunotherapy, multivariate analysis showed that only the presence of peritoneal metastases was significantly associated with shorter PFS [hazard ratios (HR), 3.23; 95% CI, 1.12-9.32; P=0.030] and the patients with peritoneal metastases had shorter median PFS than patients without peritoneal metastases(3.1 vs 18.4 months; P=0.004), while the objective response rate was 100% in patients with HER2-positive (2 complete radiographic responses and 2 partial responses; 3 of 4 patients were still ongoing benefits [median follow-up time, 15.3 months; interquartile range(IQR), 6.3-17.9 months]). Conclusions: The findings suggest that patients with various types of gastric cancer liver metastases respond differently to immune checkpoint inhibitors, HER2-positive patients may derive clinical benefits from immune checkpoint inhibitors, while the presence of peritoneal metastases is associated with resistance. [ABSTRACT FROM AUTHOR]

Tumour ablation is an established therapy for local treatment of liver metastases and hepatocellular carcinoma. Most commonly two different kind of thermic ablation, radiofrequency ablation and microwave ablation, are used in clinical practice. The aim of both is to induce thermic damage to the malignant cells in order to obtain coagulative necrosis of the neoplastic lesions. Our main concerns about these procedures are the collateral thermic damage to adjacent structures and heat-sink effect. Irreversible electroporation (IRE) is a recently developed, non-thermal ablation procedure which works applying short pulses of direct current that generate an electric field in the lesion area. The electric field increase the transmembrane potential, changing its permeability to ions. Irreversible electroporation does not generate heat, giving the chance to avoid the heatsink effect and opening the path to a better treatment of all the lesions located in close proximity to big vessels and bile ducts. Electric fields produced by the IRE may affect endothelial cells and cholangiocytes but they spare the collagen matrix, preserving re-epithelization process as well as the function of the damaged structures. Purpose of the authors is to identify the different scenarios where CT-guided percutaneous IRE of the liver should be preferred to other ablative techniques and why. [ABSTRACT FROM AUTHOR]

Tumour ablation is an established therapy for local treatment of liver metastases and hepatocellular carcinoma. Most commonly two different kind of thermic ablation, radiofrequency ablation and microwave ablation, are used in clinical practice. The aim of both is to induce thermic damage to the malignant cells in order to obtain coagulative necrosis of the neoplastic lesions. Our main concerns about these procedures are the collateral thermic damage to adjacent structures and heat-sink effect. Irreversible electroporation (IRE) is a recently developed, non-thermal ablation procedure which works applying short pulses of direct current that generate an electric field in the lesion area. The electric field increase the transmembrane potential, changing its permeability to ions.Irreversible electroporation does not generate heat, giving the chance to avoid the heat-sink effect and opening the path to a better treatment of all the lesions located in close proximity to big vessels and bile ducts. Electric fields produced by the IRE may affect endothelial cells and cholangiocytes but they spare the collagen matrix, preserving re-epithelization process as well as the function of the damaged structures. Purpose of the authors is to identify the different scenarios where CT-guided percutaneous IRE of the liver should be preferred to other ablative techniques and why.

BackgroundThe present work evaluated how Peking prognostic score (PPS), the new prognostic index determined according to sarcopenia and lymphocyte-to-C-reactive protein ratio (LCR), was a prognostic factor for patients with gastric cancer liver metastases (GCLM) who received hepatectomy.MethodsThis work extracted information about patients with GCLM who underwent hepatectomy from June 2012 to May 2018. The PPS of the patients was calculated from sarcopenia status and LCR before surgery, and patients were then divided into three groups based on their PPS. This work also carried out univariate and multivariate analyses for identifying variables that were linked with overall survival (OS) together with recurrence-free survival (RFS) after hepatectomy among three groups according to PPS.ResultsThis work included 108 GCLM cases who received hepatectomy. All cases were classified into 3 groups, i.e., 26 (24.1%), 48 (44.4%), and 34 (31.5%) in groups 0–2, separately. PPS exhibited positive relation with age (p < 0.001), body mass index (BMI; p = 0.012), and liver metastasis number. The relapse rate after hepatectomy in patients with GCLM was 69.4%. Additionally, the remnant liver relapse rates of groups 0–2 were 80.0, 68.7, and 53.5%. Patients in group 0 had significantly increased remnant liver relapse rates when compared with those in groups 0 and 1. PPS was significantly related to relapse patterns (p = 0.003). Relative to group 0, those of the other 2 groups showed dismal OS [hazard ratio (HR) = 3.98, 7.49 for groups 1 and 2; p < 0.001] along with RFS (HR = 3.65, 5.33 for groups 1 and 2; p < 0.001). As revealed by multivariate analysis, PPS independently predicted OS (p < 0.001) together with RFS (p < 0.001).ConclusionThe PPS could be an easy nutrition-inflammation prognostic scoring system and an independent preoperative predictor of survival for GCLM cases after hepatectomy.

Lung cancer is a malignant tumor with the highest morbidity and mortality, and more than 75% of patients are diagnosed at an advanced stage. Liver metastases occur in 20% of non-small cell lung cancer patients, and their prognosis are poor. In recent years, immune checkpoint inhibitor monotherapy and combination therapy have made breakthrough progress in advanced Non-small cell lung cancer (NSCLC) patients. However, compared with the overall population, the liver metastases population was an independent prognostic factor for poor immunotherapy response. Whether and how immunotherapy can work in NSCLC patients with liver metastases is a major and unresolved challenge. Although more and more data have been disclosed, the research progress of NSCLC liver metastasis is still limited. How liver metastasis modulates systemic antitumor immunity and the drug resistance mechanisms of the liver immune microenvironment have not been elucidated. We systematically focused on non-small cell lung cancer patients with liver metastases, reviewed and summarized their pathophysiological mechanisms, immune microenvironment characteristics, and optimization of immunotherapy strategies. [ABSTRACT FROM AUTHOR]

Background: The genomic features of cancer cells may confer the metastatic ability of lung adenocarcinoma (LUAD) to metastasize to specific organs. We aimed to identify the differences in genomic alterations between patients with primary LUAD with and without metastases and to elucidate the metastatic biology that may help developing biomarkerdirected therapies for advanced or metastatic disease. Methods: A retrospective cohort of 497 patients with LUAD including 388 primary tumors (PR), 53 bone metastases (MT-bone), 30 liver metastases (MT-liver), and 26 brain metastases (MT-brain) was tested for genomic alterations by a next-generation sequencing assay. Results: The EGFR, TP53, TERT, LRP1B, CDKN2A, ERBB2, ALK, and KMT2C genes had a high frequency of mutations, and the mutations were shared by PR and metastases groups. TP53 and EGFR were the most common mutated genes. In comparison with PR, KRAS, STK11, ATM, NPM1, and ROS1 were significantly mutated in MT-brain, and TP53, MYC, RSPO2, CDKN2a, and CDKN2B were significantly mutated in MT-liver. The frequencies of TP53, CDKN2A, MTAP, PRKCI, and APC mutations were higher in MTbone than that in PR. The ERBB, phosphoinositide-3-kinase/protein kinase B (PI3K-AKT), cell cycle, Fibroblast growth factor (FGF), and homologous recombination deficiency signaling pathways were affected in both PR and metastases, and there is higher frequency of mutations in metastases. Moreover, the co-mutations in patients with PR and metastasis were respectively analyzed. In addition, the programmed death ligand 1 (PD-L1) level was obviously related to tumor stage and tumor metastases, and the tumor mutational burden was correlated to clinicopathological features including age, gender, pathological stages, and tumor metastases. FGFR1, KAT6A, MYC, RAD21, TP53, and DAXX were also dramatically correlated to the tumor mutational burden. Conclusion: Metastases are the most devastating stage of tumors and the main cause of cancer-related deaths. Our results provided a clinically relevant view of the tumor-intrinsic mutational landscape of patients with metastatic LUAD. [ABSTRACT FROM AUTHOR]

BackgroundHepatic arterial infusion (HAI) of chemotherapy is an option for the treatment of patients with liver metastases from colorectal cancer (LMCRC). Though HAI with oxaliplatin (HAI-Ox) is generally used, intravenous (IV) 5-fluoro-uracil (5FU)-oxaliplatin-irinotecan HAI (HAI-Folfirinox) is feasible and leads to curative-intent surgery in 30% of pretreated patients. We compared the efficacy and safety of HAI-Ox and HAI-Folfirinox.MethodsPatients who underwent HAI chemotherapy for LMCRC were retrospectively included from 2008 to 2019 from six French expert centers.ResultsData were collected from 273 previously treated patients with LMCRC. Patients received HAI-Folfirinox (n = 52) or HAI-Ox (n = 221) combined with IV chemotherapy. The objective response rate (ORR) was 43.2% in patients with HAI-Folfirinox and 45.9% (ns) in patients with HAI-Ox. Median overall survival (OS) was 17 months (95% CI: 15–32.3) with HAI-Folfirinox and 26.2 months (95% CI: 19.4–34.4; p = 0.1) with HAI-Ox. Median progression-free survival (PFS) was 7.9 months (95% CI: 4.9–10.3) with HAI-Folfirinox and 6.4 months (95% CI: 6.0–7.7; p = 0.6) with HAI-Ox. The secondary liver resection rate was 35.6% with HAI-Folfirinox and 16.7% with HAI-Ox (p = 0.007). Grade 2 and above toxicities were significantly more frequent with HAI-Folfirinox. In the global population, only 2 factors were prognostic for OS in multivariable analyses: liver-only disease [hazard ratio (HR): 0.4; 95% CI 0.20–0.83; p = 0.013] and local complications of the catheter (HR: 3.8; 95% CI 1.6–9.0; p = 0.002).ConclusionHepatic arterial infusion results in high response rates, secondary resections, and long survival in pretreated patients with LMCRC.

BackgroundThe present work focused on assessing the role of computed tomography (CT)-determined sarcopenia in the prognosis of patients with gastric cancer liver metastases (GCLM) receiving hepatectomy.MethodsWe analyzed data collected from GCLM cases that underwent hepatectomy between March 2011 and July 2017. The third lumbar vertebra (L3) level skeletal muscle index (SMI) was analyzed by abdominal CT to determine the sarcopenia before surgery. The thresholds for CT-based sarcopenia of sex-specific L3 SMI were ≤ 34.9 cm2/m2 and ≤ 40.8 cm2/m2 for female and male, separately We determined overall survival (OS) and recurrence-free survival (RFS)by univariate and multivariate analyses.ResultsThe cohort enrolled altogether 114 patients with GCLM receiving hepatectomy (average age: 62.6 years, male: 79.8%), and 58 (50.8%) patients had sarcopenia. The mean SMI was 34.2 in patients with sarcopenia compared to 42.7 in patients without sarcopenia (p < 0.001). The 1-, 3-, and 5-year OS rates in patients with GCLM after hepatectomy were 78.1, 43.7, and 34.3%, respectively. The 1-, 3-, and 5-year RFS rates in patients were 49.8, 33.6, and 29.3%, respectively. Sarcopenia was related to an advanced age (≥65.0 years) (p = 0.009), reduced BMI (1) (p = 0.025). Sarcopenia had a significant associated with the patterns of recurrence (p < 0.001). In addition, patients with sarcopenia had a significant difference in number of liver metastases in comparison with those without sarcopenia (p = 0.025). We discovered from multivariate analysis that sarcopenia independently predicted RFS [hazard ratio (HR) = 1.76; 95% confidence interval (CI)= 1.18–2.35, p = 0.007]. Nevertheless, sarcopenia was not the prognostic factors that independently predicted OS (HR = 1.62; 95% CI = 0.57–2.73; p = 0.330).ConclusionsIn conclusion, we showed that CT-determined sarcopenia was the facile and effective prognostic factor for RFS inpatients with GCLM after hepatectomy. Patients with sarcopenia are associated with an increased tumor recurrence risk, and thereby customized treatment should be applied.

Objective: This study aims to assess the performance of machine learning (ML)-based contrast-enhanced CT radiomics analysis for predicating the efficacy of anti-HER2 therapy for patients with liver metastases from breast cancer. Methods: This retrospective study analyzed 83 patients with breast cancer liver metastases. Radiomics features were extracted from arterial phase, portal venous phase, and delayed phase images, respectively. The intraclass correlation coefficient (ICC) was calculated to quantify the reproducibility of features. The training and validation sets consisted of 58 and 25 cases. Variance threshold, SelectKBest, and LASSO logistic regression model were employed for feature selection. The ML classifiers were K-nearest-neighbor algorithm (KNN), support vector machine (SVM), XGBoost, RF, LR, and DT, and the performance of classifiers was evaluated by ROC analysis. Results: The SVM classifier had the highest score in portal venous phase. The results were as follows: The AUC value of the poor prognosis group in validation set was 0.865, the sensitivity was 0.77, and the specificity was 0.83. The AUC value of the good prognosis group in validation set was 0.865, the sensitivity was 0.83, and the specificity was 0.77. In arterial phase, the XGBoost classifier had the highest score. The AUC value of the poor prognosis group in validation set was 0.601, the sensitivity was 0.69, and the specificity was 0.38. The AUC value of the good prognosis group in validation set was 0.601, the sensitivity was 0.38, and the specificity was 0.69. The LR classifier had the highest score in delayed phase. The AUC value of poor prognosis group in validation set was 0.628, the sensitivity was 0.62, and the specificity was 0.67. The AUC value of the good prognosis group in validation set was 0.628, the sensitivity was 0.67, and the specificity was 0.62. Conclusion: Radiomics analysis represents a promising tool in predicating the efficacy of anti-HER2 therapy for patients with liver metastases from breast cancer. The ROI in portal venous phase is most suitable for predicting the efficacy of anti-HER2 therapy, and the SVM algorithm model has the best efficiency. [ABSTRACT FROM AUTHOR]

Importance: Currently, surgical resection of distant metastatic lesions has become the preferred treatment for select colorectal cancer (CRC) patients with liver metastasis (LM) and/or pulmonary metastasis (PM). Metastasectomy is the most common curative method. However, evidence of the factors affecting the prognosis of CRC patients after resection of LM and/or PM is still insufficient. Objective: To explore the prognostic factors of CRC patients with LM and/or PM who have undergone resection of metastatic tumors and to provide reliable selection factors for surgical treatment in patients affected by LM and/or PM from CRC. Methods: The SEER database was used to identify eligible CRC LM and/or PM patients who underwent resection of the primary tumor and distant metastases from January 1, 2010, to December 31, 2018. The Kaplan–Meier method was used to calculate survival, and comparisons were performed using the log-rank test for univariate analysis. A Cox proportional hazards regression model was used to identify prognostic factors for the multivariate analysis. The outcomes included overall survival (OS) and cancer-specific survival (CSS). Results: A total of 3,003 eligible colorectal cancer patients with LM and/or PM were included in this study. The 3-year and 5-year OS rates were 53% and 33.6%, respectively, and the 3-year and 5-year CSS rates were 54.2% and 35.3%, respectively. In the adjusted multivariate analysis, age < 65 years (OS: p=0.002, CSS: p=0.002) was associated with better long-term outcomes, and primary tumors located on the left side of the colon (OS: p=0.004, CSS: p=0.006) or rectum (OS: p=0.004, CSS: p=0.006), T3 stage (OS: p<0.001, CSS: p<0.001), number of regional lymph nodes examined ≥ 12 (OS: p<0.001, CSS: p=0.001), and CRC LM (OS: p<0.001, CSS: p<0.001) were positive prognostic factors for survival after resection of metastatic tumors. Conclusion: Age < 65 years is associated with better long-term outcomes in colorectal cancer patients with LM and/or PM, analogously to the left sided primary tumor, T3 stage, number of regional lymph nodes examined ≥ 12 and liver metastases. [ABSTRACT FROM AUTHOR]

Background: Liver metastases (LMs) are common in advanced pancreatic neuroendocrine tumor (PNET) patients. Currently, the benefit of primary tumor resection (PTR) in the setting of PNET patients with liver metastases is still controversial in several guidelines. Methods: Data were extracted from the Surveillance, Epidemiology and End Results (SEER) database to evaluate this issue. The main index of interest in our study was overall survival time. Results: Information on 536 PNET patients with liver metastases from the SEER database was identified. A total of 214 patients (PTR group) received primary tumor resection, and more than half of them (132 patients) had synchronous LM resection. The other 322 PNET patients (non-PTR group) with liver metastases did not receive primary tumor resection. A significant survival benefit was gained from PTR when compared with non-PTR patients, both in OS (72.93 ± 2.7 vs. 36.80 ± 2.22 months) and 3- or 5-year survival rates (75.1% vs. 28.9% and 67.9% vs. 22.3%, respectively). No difference was found between PTR alone and PTR with synchronous LM resection. From univariate and multivariate analyses, younger age (<65 years) and good or moderate tumor differentiation may be more important when considering primary tumor resection. However, we found that all grades of tumor differentiation could result in a better overall survival time after primary tumor resection. Conclusion: Our study suggested that primary tumor resection in pancreatic neuroendocrine patients with liver metastases could result in a longer survival time. Primary tumor resection with synchronous liver metastasis resection was not related to a better survival benefit. This treatment strategy may routinely be taken into consideration in these patients. [ABSTRACT FROM AUTHOR]

The optimal management of intrahepatic malignancies involves a multidisciplinary approach. Although surgical resection has been considered the only curative approach, the use of several minimally invasive ablative techniques has dramatically increased the last two decades, mainly due to the fact that they provide similar oncological results with significantly decreased morbidity. Among these modalities, interstitial liver brachytherapy, probably the most flexible liver ablative method, with excellent clinical data on its safety and effectiveness, is frequently not even mentioned as an option in the current peer reviewed literature and guidelines. Brachytherapy is a type of radiotherapy utilizing radionuclides that are directly inserted into the tumor. Compared to external beam radiation therapy, brachytherapy has the potential to deliver an ablative radiation dose over a short period of time, with the advantage of a rapid dose fall-off, that allows for sparing of adjacent healthy tissue. For numerous malignancies such as skin, gynecological, breast, prostate, head and neck, bladder, liver and soft-tissue tumors, brachytherapy as a monotherapy or combined with external beam radiation therapy, has become a standard treatment for many decades. This review article aims to describe the high-dose-rate liver brachytherapy technique, its selection criteria, present its advantages and disadvantages, as well as the available clinical data, in order to help physicians to explore and hopefully introduce liver brachytherapy into their clinical routine. [ABSTRACT FROM AUTHOR]