Primary Liver Tumors Research Articles

Liver transplantation for primary and secondary liver tumours. patient-level meta-analyses compared to unos conventional indications.

Liver transplant (LT) for Transplant Oncology (TO) indications is being slowly adopted worldwide and has been recommended to be incorporated cautiously due to concerns on mid-long term survival and its impact on waiting list. We conducted four systematic reviews of all series on TO indications (intrahepatic (iCC) and perihilar cholangiocarcinoma (phCC)), liver metastases from neuroendocrine tumors (NET) and colorectal cancer (CRLM)) and compared them using patient-level meta-analyses to data obtained from UNOS database considering conventional daily-practice indications. Secondary analyses were done for specific selection criteria (Mayo-like protocols for phCC, SECA-2 for CRLM and Milan criteria for NET). A total of 112.014 LT were analyzed from 2005 to 2020 from the UNOS databases and compared with 345, 721, 494 and 103 patients obtained from meta-analyses on iCC and phCC, and liver metastases from NET and CRLM, respectively. Five-years overall survival was 53,3%, 56,4%, 68,6% and 53,8%, respectively. In Mantel-Cox one-to-one comparisons, survival of TO indications was superior to combined LT, second and third LT and and not statistically significant different to LT in recipients>70 years and high BMI. Liver transplantation for TO indications has adequate 5-years survival rates, mostly when performed under the selection criteria available in literature (Mayo-like protocols for phCC, SECA-2 for CRLM and Milan for NET). Despite concerns on its impact on waiting list, some other LT indications are being performed with lower survival. These oncological patients should be given the opportunity to have a definitive curative therapy within validated criteria.

HSP90 N-terminal inhibition promotes mitochondria-derived vesicles related metastasis by reducing TFEB transcription via decreased HSP90AA1-HCFC1 interaction in liver cancer

ABSTRACT Cancer cells compensate with increasing mitochondria-derived vesicles (MDVs) to maintain mitochondrial homeostasis, when canonical MAP1LC3B/LC3B (microtubule associated protein 1 light chain 3 beta)-mediated mitophagy is lacking. MDVs promote the transport of mitochondrial components into extracellular vesicles (EVs) and induce tumor metastasis. Although HSP90 (heat shock protein 90) chaperones hundreds of client proteins and its inhibitors suppress tumors, HSP90 inhibitors-related chemotherapy is associated with unexpected metastasis. Herein, we find that HSP90 inhibitor causes mitochondrial damage but stimulates the low LC3-induced MDVs and the release of MDVs-derived EVs. However, why LC3 decreases and what is the transcriptional regulatory mechanism of MDVs formation under HSP90 inhibition remain unknown. Because TFEB (transcription factor EB) is the most important mitophagy transcription factor, and the HSP90 client HCFC1 (host cell factor C1) regulates TFEB transcription, there should be a hidden connection between TFEB, HCFC1 and HSP90 in MDVs formation. Our results support the idea that HSP90 N-terminal inhibition reduces TFEB transcription via decreased HSP90AA1-HCFC1 interaction, which prevents HCFC1 from binding to the TFEB proximal promoter region. Decreased TFEB transcription and consequently reduced LC3, ultimately promoted MDVs formation. Blocking MDVs formation with the microtubule inhibitor nocodazole (NOC) activates the HCFC1-TFEB-LC3 axis, weakens HSP90 inhibitors-induced MDVs and the release of MDVs-derived EVs, inhibits the growth of tumor cell spheres and primary liver tumors, and reduces the extravasation of cancer cells to secondary metastatic sites. Taken together, these data suggest that combination therapy should be used to reduce the metastatic risk of low TFEB-triggered-MDVs formation caused by HSP90 inhibitors.

Hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a primary liver cancer predominantly arising in individuals with chronic liver diseases such as cirrhosis or chronic hepatitis B virus (HBV) infection. Accounting for approximately 75% of primary liver tumors, HCC's global epidemiology is significantly influenced by HBV and hepatitis C virus (HCV) infections, alcohol and tobacco use, metabolic syndrome, diabetes, obesity, and aflatoxin B1 exposure. Preventive measures, including HBV vaccination and direct-acting antivirals for HCV, have reduced incidence rates, particularly in younger populations. Early diagnosis through surveillance in high-risk groups is critical, employing imaging modalities like ultrasound, CT, and MRI, alongside biomarkers such as alpha-fetoprotein (AFP). Prognostic assessments utilize scores like Child-Pugh and ALBI. Treatment strategies for HCC are multifaceted, involving surgical resection, locoregional therapies (e.g., transarterial chemoembolization), and systemic therapies, including targeted and immunotherapies. Despite advancements, treatment efficacy remains a challenge, necessitating ongoing research into novel therapeutic approaches and predictive biomarkers to enhance personalized treatment and improve outcomes for HCC patients.

Prognostic Impact of the Cholangiolar Component in Combined Hepatocellular-Cholangiocarcinoma: Insights From a Western Single-Center Study.

Primary liver malignancies, such as hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), and combined hepatocellular-cholangiocarcinoma (cHCC-CCA), represent significant contributors to global cancer-related mortality. The diagnostic challenges associated with distinguishing cHCC-CCA from HCC and ICC stem from their rarity and overlapping histological features. This study aimed to reclassify primary liver tumors resected at a Western center and to compare clinicopathological features and prognosis among patients with HCC, ICC, and cHCC-CCA. A retrospective analysis was conducted on patients undergoing resection for HCC, ICC, or cHCC-CCA between 2007 and 2017. Clinical and perioperative data were collected, and pathological specimens were reclassified by a specialized pathologist. Statistical analysis was employed to compare clinical features and survival outcomes among the different tumor types. Out of the initially identified 192 patients, 140 were included in the analysis. Following reclassification, 71.42% were diagnosed with HCC, 12.14% with ICC, and 16.42% with cHCC-CCA. Patients with HCC were predominantly male and exhibited a higher incidence of isolated liver recurrence. ICC patients more frequently underwent open procedures. Additionally, patients with HCC and cHCC-CCA showed higher rates of cirrhosis, elevated alpha-fetoprotein levels, and extrahepatic recurrence, while those with ICC and cHCC-CCA demonstrated elevated CA 19-9 levels. Overall survival and disease-free survival were longer for HCC compared to cases with a cholangiolar component (ICC and cHCC-CCA). Histological evaluation should actively incorporate the search for a cholangiolar component in primary liver tumors to prevent misdiagnosis, as its presence indicates a poorer prognosis.

Evaluating glycocalyx morphology and composition in frozen and formalin-fixed liver tumor sections

BackgroundThe glycocalyx (GCX) is a glycan structure on the vascular endothelium and cancer cells. It is crucial for blood flow regulation, tumor invasion, and cancer drug resistance. Understanding the role of GCX in human tumors could help develop new cancer biomarkers and therapies. AimThis study aimed to demonstrate microstructural changes in human primary and metastatic liver tumors (henceforth termed liver tumors) by visualizing GCX using surgical specimens and comparing formalin-fixed paraffin-embedded sections (FFPEs) with frozen sections. The results of lectin staining were also compared between frozen and FFPE specimens to determine which was more useful for accurately assessing GCX structure and composition. MethodsLiver tumors and normal tissue samples from three patients were collected and processed into FFPEs and frozen sections, respectively. Lanthanum nitrate staining and scanning electron microscopy (SEM) were used to assess the GCX structures. Twenty lectins were analyzed for their glycan components in the samples. ResultsSEM revealed significant differences in GCX morphology among the cancer specimens. Frozen sections provided a more accurate GCX evaluation than FFPEs, showing distinct glycan compositions in hepatocellular carcinoma, colorectal carcinoma liver metastases, and melanoma liver metastases. Hepatocellular carcinoma samples exhibited a loss of N-acetylgalactosamine-related lectins. ConclusionThe results revealed that liver tumors have distinct and bulky GCX compared to normal liver tissue, while frozen sections are more reliable for GCX evaluation. These findings highlight glycan alterations in liver tumors and contribute to the development of new cancer therapies targeting GCX on tumor cell surfaces.

The role of ALBI score in patients treated with stereotactic body radiotherapy for locally advanced primary liver tumors: a pooled analysis of two prospective studies.

To evaluate the outcomes after stereotactic body radiotherapy (SBRT) for locally advanced primary liver cancer. Patients with locally advanced liver cancer unsuitable for other loco-regional treatments were treated with SBRT with 50-60 Gy in 3-12 fractions in two consecutive prospective trials. A total of 83 patients were included, of whom 14 were excluded, leaving 69 evaluable patients with 74 treated lesions. A total of 50 patients had hepatocellular carcinoma (HCC), and 11 patients had cholangiocarcinoma (CCC). Approximately 76% had a Child-Pugh (CP) score of A, while 54% had an albumin-bilirubin (ALBI) score of 1. With a median follow-up of 29 months, the median overall survival (OS) was 11 months, and the progression-free survival (PFS) was 18 months. The ALBI score was an important predictor of overall survival (HR 2.094, p = 0.001), which remained significant also in the multivariate analysis. Patients with an ALBI grade of ≥1 had an OS of 4 months versus 23 months in patients with an ALBI grade of 1 (p ≤ 0.001). The local control at 1 and 2 years was 91%. Thirteen patients developed grade ≥ 3 toxicities, of whom nine patients experienced liver toxicities. Patients with a higher ALBI score had a high risk for developing hepatic failure (OR 6.136, p = 0.006). SBRT is a very effective treatment with low toxicity and should be considered as a local treatment option in patients with HCC and CCC. Patients with a higher ALBI grade are at risk for developing toxicities after SBRT and have a significantly lower survival rate.

Evaluating preoperative coagulation panels in dogs undergoing liver lobectomy for primary liver tumors: A multi-institutional retrospective study.

The objectives of this study were to: (i) Determine whether operable primary liver tumors were associated with prolongations in prothrombin time (PT) and activated partial thromboplastin time (aPTT) and (ii) determine if these secondary hemostatic abnormalities were more prevalent with specific liver tumors. Multi-institutional retrospective study. Dogs (n = 359) undergoing liver lobectomy for a primary liver tumor with a preoperative coagulation panel. Data was identified via electronic medical record review at eight veterinary teaching hospitals. Baseline dog characteristics, coagulation panel values, platelet count, emergency versus non-emergency procedure, whether the dogs received transfusion(s) of a blood product, liver lobe removed, and histopathological diagnosis were extracted from the medical record. Chi-square analysis was used to compare categorical variables between groups. Continuous variables were assessed for normality using the Shapiro-Wilk test. A total of 74 of 359 dogs (20.6%) had a prolongation in either PT or aPTT preoperatively. A total of 20 of 359 dogs (5.6%) were found to have prolongation of both PT and aPTT. Hemangiosarcoma was the only histopathological diagnosis associated with concurrent prolongations of both PT and aPTT (p < .001) in 6/16 (37.5%) dogs. Coagulation panels including PT and aPTT are unlikely to detect substantial deficiencies in secondary hemostasis in most dogs with primary liver tumors except in dogs with a histopathological diagnosis of hemangiosarcoma. PT and aPTT testing is low yield as an elective preoperative screening test in dogs with primary liver tumors except in dogs where there is a hemoabdomen or high suspicion for hepatic hemangiosarcoma.

Application of a single-cell-RNA-based biological-inspired graph neural network in diagnosis of primary liver tumors

Single-cell technology depicts integrated tumor profiles including both tumor cells and tumor microenvironments, which theoretically enables more robust diagnosis than traditional diagnostic standards based on only pathology. However, the inherent challenges of single-cell RNA sequencing (scRNA-seq) data, such as high dimensionality, low signal-to-noise ratio (SNR), sparse and non-Euclidean nature, pose significant obstacles for traditional diagnostic approaches. The diagnostic value of single-cell technology has been largely unexplored despite the potential advantages. Here, we present a graph neural network-based framework tailored for molecular diagnosis of primary liver tumors using scRNA-seq data. Our approach capitalizes on the biological plausibility inherent in the intercellular communication networks within tumor samples. By integrating pathway activation features within cell clusters and modeling unidirectional inter-cellular communication, we achieve robust discrimination between malignant tumors (including hepatocellular carcinoma, HCC, and intrahepatic cholangiocarcinoma, iCCA) and benign tumors (focal nodular hyperplasia, FNH) by scRNA data of all tissue cells and immunocytes only. The efficacy to distinguish iCCA from HCC was further validated on public datasets. Through extending the application of high-throughput scRNA-seq data into diagnosis approaches focusing on integrated tumor microenvironment profiles rather than a few tumor markers, this framework also sheds light on minimal-invasive diagnostic methods based on migrating/circulating immunocytes.

CT and MR imaging characteristics of primary hepatic lymphoma

BackgroundPrimary hepatic lymphoma (PHL) is a rare primary liver tumor. The purpose of this study was to investigate the crucial imaging characteristics of PHL.MethodsCT/MR data and clinical features of 16 patients with pathologically proven PHL were retrospectively reviewed. The assessed imaging characteristics included lesion distribution, growth appearance, density or signal characteristics, and typical signs during the dynamic enhancement.ResultsA total of sixteen patients were included in this study, ranging in age from 27 to 86 years (nine men and seven women; mean age, 62 years). Right upper abdominal pain, malaise, or first detection during physical examination were the chief complaint. Dynamic contrast-enhanced CT and MRI demonstrated focal masses in thirteen patients (13/16, 81%), and multiple nodules in three patients (3/16, 19%). The lesions showed vascular floating sign in 10 patients (10/16, 63%) and biliary pass-through sign in 6 patients (6/16, 37%). Necrosis in PHLs were observed in 10 patients (10/16, 63%) and presented target sign on T2WI in 5 out of 11 patients (5/11, 45%) undergoing MRI. After enhancement, PHLs had multinodular sign in the arterial phase in 10 patients (10/16, 63%), and presented washout of contrast medium in the portal-venous or delayed phase in 12 patients (12/16, 75%), pseudocapsule in the delayed phase in 15 patients (15/16, 94%), and double-ring sign in the delayed phase in 8 patients (8/16, 50%).ConclusionPHL is generally seen in elderly patients with elevated beta-2-microglobulin levels. Its distinctive imaging features including obviously low ADC value, biliary/vascular floating sign, multinodular sign and double-ring sign in the delayed phase, may help to diagnose and differentiate PHL.

Causal Effect of Immunocytes, Plasma Metabolites, and Hepatocellular Carcinoma: A Bidirectional Two-Sample Mendelian Randomization Study and Mediation Analysis in East Asian Populations.

Background: Hepatocellular carcinoma (HCC) is a primary malignant liver tumor characterized by a low survival rate and high mortality. This study aimed to investigate the causal effect of immune cell phenotypes, plasma metabolites, and HCC in East Asian populations. Methods: The summary results for 731 immunocytes, 1400 plasma metabolites, and HCCs were acquired from publicly available genome-wide association studies (GWASs). This study utilized two-sample Mendelian randomization (MR) analysis to establish causal relationships, which was achieved by employing various statistical methods including inverse variance-weighted, simple mode, MR-Egger, weighted median, and weighted mode. Multiple sensitivity analyses were conducted to confirm the reliability of the MR data. Ultimately, mediation analysis was employed to ascertain the path that leads from immunocytes to plasma metabolites. Results: Among the 20 immune cells and HCC for East Asians, causal links were found, with one showing an inverse correlation. In addition, 36 metabolites were significantly associated with HCC for East Asians. Through analysis of established causative metabolites, we identified a strong correlation between the glycerophospholipid metabolic pathway and HCC for East Asians. By employing a two-step MR analysis, we identified 11 immunocytes that are causally linked to HCC for East Asians through the mediation of 14 plasma metabolites, with Linolenate [α or γ; (18:3n3 or 6)] levels showing the highest mediation proportion (19.3%). Conclusions: Our findings affirm the causal links among immunocytes, plasma metabolites, and HCC in eastern Asia populations by calculating the percentage of the impact that is influenced by plasma metabolites. This study offers innovative perspectives on the early detection, diagnosis, and therapy of HCC.

HSF1 is a prognostic determinant and therapeutic target in intrahepatic cholangiocarcinoma

BackgroundIntrahepatic cholangiocarcinoma (iCCA) is a lethal primary liver tumor characterized by clinical aggressiveness, poor prognosis, and scarce therapeutic possibilities. Therefore, new treatments are urgently needed to render this disease curable. Since cumulating evidence supports the oncogenic properties of the Heat Shock Factor 1 (HSF1) transcription factor in various cancer types, we investigated its pathogenetic and therapeutic relevance in iCCA.MethodsLevels of HSF1 were evaluated in a vast collection of iCCA specimens. The effects of HSF1 inactivation on iCCA development in vivo were investigated using three established oncogene-driven iCCA mouse models. In addition, the impact of HSF1 suppression on tumor cells and tumor stroma was assessed in iCCA cell lines, human iCCA cancer-associated fibroblasts (hCAFs), and patient-derived organoids.ResultsHuman preinvasive, invasive, and metastatic iCCAs displayed widespread HSF1 upregulation, which was associated with a dismal prognosis of the patients. In addition, hydrodynamic injection of a dominant-negative form of HSF1 (HSF1dn), which suppresses HSF1 activity, significantly delayed cholangiocarcinogenesis in AKT/NICD, AKT/YAP, and AKT/TAZ mice. In iCCA cell lines, iCCA hCAFs, and patient-derived organoids, administration of the HSF1 inhibitor KRIBB-11 significantly reduced proliferation and induced apoptosis. Cell death was profoundly augmented by concomitant administration of the Bcl-xL/Bcl2/Bcl-w inhibitor ABT-263. Furthermore, KRIBB-11 reduced mitochondrial bioenergetics and glycolysis of iCCA cells.ConclusionsThe present data underscore the critical pathogenetic, prognostic, and therapeutic role of HSF1 in cholangiocarcinogenesis.

HKDC1 promotes liver cancer stemness under hypoxia through stabilizing β-catenin.

Hexokinases (HKs), a group of enzymes catalyzing the first step of glycolysis, have been shown to play important roles in liver metabolism and tumorigenesis. Our recent studies identified hexokinase domain containing 1 (HKDC1) as a top candidate associated with liver cancer metastasis. We aimed to compare its cell-type specificity with other HKs upregulated in liver cancer and investigate the molecular mechanisms underlying its involvement in liver cancer metastasis. We found that, compared to HK1 and HK2, the other 2 commonly upregulated HKs in liver cancer, HKDC1 was most strongly associated with the metastasis potential of tumors and organoids derived from 2 liver cancer mouse models we previously established. RNA in situ hybridization and single-cell RNA-seq analysis revealed that HKDC1 was specifically upregulated in malignant cells in HCC and cholangiocarcinoma patient tumors, whereas HK1 and HK2 were widespread across various tumor microenvironment lineages. An unbiased metabolomic profiling demonstrated that HKDC1 overexpression in HCC cells led to metabolic alterations distinct from those from HK1 and HK2 overexpression, with HKDC1 particularly impacting the tricarboxylic acid cycle. HKDC1 was prometastatic in HCC orthotopic and tail vein injection mouse models. Molecularly, HKDC1 was induced by hypoxia and bound to glycogen synthase kinase 3β to stabilize β-catenin, leading to enhanced stemness of HCC cells. Overall, our findings underscore HKDC1 as a prometastatic HK specifically expressed in the malignant compartment of primary liver tumors, thereby providing a mechanistic basis for targeting this enzyme in advanced liver cancer.

Inter-observer reliability and predictive values of triphasic computed tomography for microvascular invasion in hepatocellular carcinoma

BackgroundHepatocellular carcinoma (HCC) is the most frequent primary liver tumor globally and a leading cause of mortality in cirrhotic patients. Our study aimed to estimate the diagnostic performance of triphasic CT and inter-observer reliability in the preoperative detection of microvascular invasion (MVI) in HCC. Two independent radiologists accomplished a retrospective analysis for 99 patients with HCC to assess the CT features for MVI in each lesion. Postoperative histopathology was considered the gold standard.ResultsMultivariate regression analysis revealed that incomplete or absent tumor capsules, presence of TTPV, and absence of hypodense halo were statistically significant independent predictors of MVI. There was excellent agreement among observers in evaluating peritumoral enhancement, identifying intratumoral arteries, hypodense halo, TTPV, and macrovascular invasion. Also, our results revealed moderate agreement in assessing the tumor margin and tumor capsule.ConclusionTriphasic CT features of MVI are reliable imaging predictors that may be helpful for standard preoperative interpretation of HCC.

The #HOPE4LIVER Single-Arm Pivotal Trial for Histotripsy of Primary and Metastatic Liver Tumors.

Background Histotripsy is a nonthermal, nonionizing, noninvasive, focused US technique that relies on cavitation for mechanical tissue breakdown at the focal point. Preclinical data have shown its safety and technical success in the ablation of liver tumors. Purpose To evaluate the safety and technical success of histotripsy in destroying primary or metastatic liver tumors. Materials and Methods The parallel United States and European Union and England #HOPE4LIVER trials were prospective, multicenter, single-arm studies. Eligible patients were recruited at 14 sites in Europe and the United States from January 2021 to July 2022. Up to three tumors smaller than 3 cm in size could be treated. CT or MRI and clinic visits were performed at 1 week or less preprocedure, at index-procedure, 36 hours or less postprocedure, and 30 days postprocedure. There were co-primary end points of technical success of tumor treatment and absence of procedure-related major complications within 30 days, with performance goals of greater than 70% and less than 25%, respectively. A two-sided 95% Wilson score CI was derived for each end point. Results Forty-four participants (21 from the United States, 23 from the European Union or England; 22 female participants, 22 male participants; mean age, 64 years ± 12 [SD]) with 49 tumors were enrolled and treated. Eighteen participants (41%) had hepatocellular carcinoma and 26 (59%) had non-hepatocellular carcinoma liver metastases. The maximum pretreatment tumor diameter was 1.5 cm ± 0.6 and the maximum post-histotripsy treatment zone diameter was 3.6 cm ± 1.4. Technical success was observed in 42 of 44 treated tumors (95%; 95% CI: 84, 100) and procedure-related major complications were reported in three of 44 participants (7%; 95% CI: 2, 18), both meeting the performance goal. Conclusion The #HOPE4LIVER trials met the co-primary end-point performance goals for technical success and the absence of procedure-related major complications, supporting early clinical adoption. Clinical trial registration nos. NCT04572633, NCT04573881 Published under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Nezami and Georgiades in this issue.

1024: Predictive factors of liver toxicity after SBRT of primary liver tumors

1024: Predictive factors of liver toxicity after SBRT of primary liver tumors

Locoregional Treatments in Peritoneal Metastasis from Gastric Cancer

Background: Liver cancer is among the top five causes of cancer death globally. Hepatocellular Carcinoma (HCC) accounts for up to 90% of primary liver neoplasms in adults. The incidence of thyroid me-tastasis from HCC is rare and estimated from 0.8 to 12%. This report describes a 51-year-old man presenting with hypercalcemia and known metastatic HCC with new metastasis to the thyroid gland. Case Report: A 51-year-old male was admitted due to symptomatic hypercalcemia. His medical history included HCC with metastasis to the retroperitoneal lymph nodes diagnosed one year prior. Computed tomography revealed an enlarging liver mass, diffuse lymphadenopathy and many osseous lytic lesions. Ultrasound of the neck revealed abnormal right cervical lymph nodes and a heterogeneous mass replacing the right thyroid gland. Biopsy of the right cervical lymph node immunohistochemical stained positive for PAN-K, Glypican-3, HepPar1 and Anti-Arginase and negative for p40 and CEA-poly, supporting the diagnosis for metastatic HCC. His hospital course was complicated by dysphagia, spontaneous bacterial peritonitis and acute-on-chronic liver failure. Despite aggressive resuscitation, he continued to decline and ultimately pursued hospice care. Conclusion: This case illustrates the need to have a high index of suspicion for thyroid metastasis in HCC patients presenting with a new-onset cervical mass, dysphagia or hypercalcemia. Metastatic cancer to the thyroid gland is generally considered a poor prognostic factor, as seen in this case with the rapid decline. This case demonstrates an extremely rare presentation of HCC with metastasis to the thyroid gland.

Outcome and Survival Analysis of Multicenter Lung Metastasectomy for Primary Liver Tumor with Pulmonary Metastasis.

Oligopulmonary metastases from primary liver tumors are typically treated surgically. We evaluated the clinical outcomes after lung metastasectomy in patients with pulmonary metastases from primary liver tumors. We retrospectively enrolled 147 consecutive patients with lung metastases from liver cancer who had undergone pulmonary metastasectomies at three medical centers between February 2007 and December 2020. All patients were pathologically confirmed to have lung metastases from liver cancer. Among the 147 patients, 110, 17, and 20 initially underwent surgical resection, radiofrequency ablation, and transcatheter arterial embolization, respectively. The 5-year overall survival (OS) in the study cohort was 22%. Univariate analysis revealed four factors associated with better OS: surgical resection as the initial primary liver tumor treatment (p = 0.004), a disease-free interval exceeding 12 months after the initial liver surgery (p = 0.036), a lower Model for End-Stage Liver Disease (MELD)-Na score (≤20) for liver cirrhosis (p = 0.044), and the absence of local liver tumor recurrence at the time of pulmonary metastasectomy (p = 0.004). Multivariate analysis demonstrated that surgical resection as the initial primary liver tumor treatment and lower MELD-Na scores significantly correlated with better OS. Our findings can assist thoracic surgeons in selecting suitable patients for surgery and predicting surgical outcomes.

Voxel-based dosimetry with integrated Y-90 PET/MRI and prediction of response of primary and metastatic liver tumors to radioembolization with Y-90 glass microspheres.

In this study, we aimed to evaluate the response of the primary and metastatic liver tumors to radioembolization with 90Y glass microspheres and investigate its correlations with dosimetric variables calculated with 90Y PET/MRI. In this ambispective study, 44 patients treated with 90Y glass microspheres and imaged with 90Y PET/MRI were included for analysis. Dosimetric analysis was performed for every perfused lesion using dose-volume histograms. Response was assessed by comparing pre-treatment and follow-up total lesion glycolysis (TLG) values derived from 18F-FDG PET imaging. The relationship between ΔTLG and log-transformed dosimetric variables was analyzed with linear mixed effects regression models. ROC analyses were performed to compare discriminatory power of the variables in predicting response and complete response. Regression and ROC analyses demonstrated that mean tumor dose and almost all D values were statistically significant predictors of treatment response and complete treatment response. Specifically, D60, D70 and D80 values exhibited significantly higher discriminatory power for predicting treatment response compared to the mean dose (Dmean) delivered to tumor. High specificity cut-off values to predict response were determined as 160.75 Gy for Dmean, 95.50 Gy for D60, 89 Gy for D70, and 59.50 Gy for D80. Similarly, high-specificity cut-off values to predict complete response were 262.75 Gy for Dmean, 173 Gy for D70, 140.5 Gy for D80, and 100 Gy for D90. In this study, we demonstrated that voxel-based dosimetry with post-treatment 90Y PET/MRI can predict response to treatment. D60, D70 and D80 variables also did have greater discriminatory power compared to Dmean in prediction of response. In addition, we present high-specificity cut-offs to predict response (CR + PR) and complete response (CR) for both Dmean and several D variables derived from dose-volume histograms.

CCL2 Predicts Survival in Patients with Inoperable Hepatocellular Carcinoma Undergoing Selective Internal Radiotherapy.

Hepatocellular carcinoma (HCC) is the largest subgroup of primary liver tumors. Ablative therapies, such as selective internal radiation therapy (SIRT), are used in late stages for patients with unresectable liver metastases and no response to other therapies. CCL2 (C-C motif chemokine ligand 2) is a potent monocyte chemoattractant. It is associated with tumor progression and metastasis. The role of circulating CCL2 as a biomarker in HCC undergoing selective internal radiation therapy remains unclear. A total of 41 patients (8 female, 33 male) suffering from HCC and undergoing SIRT were enrolled. Pre- and post-therapy changes in circulating CCL2 levels were determined by bead-based immunoassay and compared with clinical laboratory parameters and patient data. A total of 32 patients exhibited survival beyond 60 days. It was observed that levels of CCL2 correlated with scores indicating a higher likelihood of non-survival and with the severity of the disease. Moreover, a significant inverse correlation was discovered between CCL2 levels and the survival of patients over 60 days in relation to counts of leukocytes, granulocytes, monocytes, and C-reactive protein. CCL2 may serve as a potential marker for patient survival after SIRT. The prediction of which HCC patients are likely to benefit from SIRT may be helpful in guiding therapeutic management.

Arterial hypoperfusion as a negative predictive marker for primary hepatic malignancies treated with Y-90 glass microsphere transarterial radioembolization.

Radioembolization with yttrium-90 (Y-90) is utilized to treat primary liver malignancies. The efficacy of this intra-arterial therapy in arterially hypoperfused tumors is not known. We reviewed data of patients with primary liver tumors treated with Y-90 prescription doses of at least 150 Gy. Baseline patient characteristics, treatment history, imaging-based tumor response assessments, and clinical outcome metrics were recorded. Tumors were classified as arterially hyperperfused versus hypoperfused on post-TARE Y-90 SPECT/CTs or pre-TARE hepatic perfusion SPECT/CTs. Perfusion status was correlated with tumor response assessments and clinical outcomes. Cox proportional hazards models were utilized to compare survival and progression-free survival. Inverse probability weighting was utilized to account for clinical factors and adjusted multivariable proportional hazards analyses to examine the relationship of quantitative perfusion and cancer outcomes. Of 400 Y-90 treatments, 88 patients received a prescribed dose of at least 150 Gy and had pre- or post-treatment SPECT/CT images. 11 and 77 patients had arterially hypoperfused and hyperperfused lesions, respectively. On dedicated liver MRI or CT at 3 months after Y-90, the complete response rates were 5.6% and 16.5% in the hypoperfused and hyperperfused cohort, respectively (P = 0.60). When controlling for various clinical features, including tumor histology, patients with arterially hypoperfused tumors had significantly shorter progression-free survival (HR 1.87, 95% CI - 1.03 - 3.37, P = 0.039) and greater elsewhere liver (HR 3.36, 95% CI = 1.23 - 9.20, P = 0.019) and distant failure (HR 7.64 (2.71 - 21.54, P < 0.001). In inverse probability weighted analysis, patients with arterially hypoperfused tumors had worse overall survival (P = 0.032). In the quantitative analysis, lower levels of lesion perfusion were also associated with worse clinical outcomes, again controlling for tumor histology. Compared to arterially hyperperfused tumors, hypoperfused primary liver tumors treated with Y-90 may have worse clinical outcomes.