Metastatic Liver Lesions Research Articles

Leukemoid Reaction in an Elderly Patient with Aortic Valve Infective Endocarditis and Pancreatic Adenocarcinoma

Leukemoid reaction (LR) associated with solid tumors has been documented for many decades. LR is often associated with an unfavorable prognosis and aggressive course of the disease. However, the differential diagnosis of LR is of significant difficulty when a patient has several potential etiological factors, each of them individually may cause LR or, on the contrary, lead to a systemic reaction of the body within a single pathogenetic chain.We present a clinical observation of an elderly patient admitted to the intensive care unit due to the first-time encountered weakness in the right extremities. Clinical and instrumental examination revealed an acute cerebral ischemia with leukocytosis increase up to 60.000 cells/μL with leukocyte formula left shift and subsequent patient decompensation with lethal outcome, despite the intensive treatment.Autopsy revealed a low-differentiated adenocarcinoma of the pancreatic tail with multiple metastatic lesions in regional lymph nodes and liver, as well as a competing disease — acute infective endocarditis of the aortic valve, which was the cause of sepsis development with septicemia type and thromboembolism both in the great circulation circle with the presence of ischemic cerebral infarction, spleen infarcts, and in the small circle with the development of thromboembolism in the right segmental branches of the pulmonary artery. Given the advanced stage of pancreatic cancer and lack of direct evidence of sepsis at primary diagnosis, paraneoplastic nature of LR is more likely, but infective endocarditis and concomitant pathology also may have contributed to the development of LR.

Intraoperative contrast-enhanced ultrasound has an outcome-relevant impact on surgery of primary and metastatic liver lesions

Abstract Purpose Complete resection of the affected tissue remains the best curative treatment option for liver-derived tumors and colorectal liver metastases. In addition to preoperative cross-sectional imaging, contrast-enhanced intraoperative ultrasound (CE-IOUS) plays a crucial role in the detection and localization of all liver lesions. However, its exact role is unclear. This study was designed to evaluate the clinical and oncological impact of using CE-IOUS in the surgical treatment of these diseases. Materials and Methods Over the three-year study period, 206 patients with primary liver tumors and hepatic metastases were enrolled in this prospective, monocentric study to evaluate the impact of CE-IOUS in liver surgery. Secondary outcomes included comparing the sensitivity and specificity of CE-IOUS with existing preoperative imaging modalities and identifying preoperative parameters that could predict a strategic impact of CE-IOUS. In addition, the oncological significance of CE-IOUS was evaluated using a case-cohort design with a minimum follow-up of 18 months. Results CE-IOUS findings led to a change in surgical strategy in 34% of cases (n=70/206). The accuracy in cases with a major change could be confirmed histopathologically in 71.4% of cases (n=25/35). The impact could not be predicted using parameters assumed to be clinically relevant. An oncological benefit of a CE-IOUS adapted surgical approach was demonstrated in patients suffering from HCC and colorectal liver metastases. Conclusion CE-IOUS may significantly increase R0 resection rates and should therefore be used routinely as an additional staging method, especially in complex liver surgery.

Combined Therapy of Chemotherapy and Radiofrequency Ablation for Pancreatic Cancer Patients With Metachronous Hepatic Metastatic Lesions After Radical Pancreatic Resection.

Hepatic metastasis frequently occurs in patients who have undergone radical pancreatic resection for pancreatic cancer. Besides chemotherapy, various local treatment approaches targeting hepatic lesions have been explored. However, research on radiofrequency ablation (RFA) as a localized therapy for hepatic metastasis is limited. Therefore, we conducted this retrospective study to provide clinical evidence. This is a single-center, retrospective, cohort study. After radical pancreaticoduodenectomy, 32 patients developed metachronous hepatic metastasis with fewer than 3 lesions, the largest of which was less than 3cm in diameter. These patients underwent combined treatment with chemotherapy and RFA. After 8 weeks of chemotherapy, patients received RFA for hepatic lesions. Additional chemotherapy was administered, and the patients' tumor status and survival were monitored. The primary endpoint of this study was overall survival (OS). Factors affecting OS were analyzed using the Cox risk model. Among the 32 patients, the mean OS was 28.4 months. Univariate and multivariate Cox regression analysis revealed that the time (in months) of liver metastasis (HR = 0.04, 95% CI: 0.01 to 0.19; P < 0.001), the number of liver metastases (HR = 7.08, 95% CI: 1.85 to 27.08, P = 0.004), and PD (progressive disease) response to the second round of chemotherapy (HR = 29.50, 95% CI: 1.46 to 597.27; P = 0.027) were independent predictors of poorer survival. Combined therapy with RFA and chemotherapy is safe in patients with hepatic metastasis after radical pancreaticoduodenectomy. Early recurrence (≤12months), three liver metastatic lesions, and a poor response to the second round of chemotherapy were associated with poor survival.

Molecular mechanisms of pancreatic cancer liver metastasis: the role of PAK2.

Pancreatic cancer remains an extremely malignant digestive tract tumor, posing a significant global public health burden. Patients with pancreatic cancer, once metastasis occurs, lose all hope of cure, and prognosis is extremely poor. It is important to investigate liver metastasis of Pancreatic cancer in depth, not just because it is the most common form of metastasis in pancreatic cancer, but also because it is crucial for treatment planning and prognosis assessment. This study aims to delve into the mechanisms of pancreatic cancer liver metastasis, with the goal of providing crucial scientific groundwork for the development of future treatment methods and drugs. We explored the mechanisms of pancreatic cancer liver metastasis using single-cell sequencing data (GSE155698 and GSE154778) and bulk data (GSE71729, GSE19279, TCGA-PAAD). Initially, Seurat package was employed for single-cell data processing to obtain expression matrices for primary pancreatic cancer lesions and liver metastatic lesions. Subsequently, high-dimensional weighted gene co-expression network analysis (hdWGCNA) was used to identify genes associated with liver metastasis. Machine learning algorithms and COX regression models were employed to further screen genes related to patient prognosis. Informed by both biological understanding and the outcomes of algorithms, we meticulously identified the ultimate set of liver metastasis-related gene (LRG). In the study of LRG genes, various databases were utilized to validate their association with pancreatic cancer liver metastasis. In order to analyze the effects of these agents on tumor microenvironment, we conducted an in-depth analysis, including changes in signaling pathways (GSVA), cell differentiation (pseudo-temporal analysis), cell communication networks (cell communication analysis), and downstream transcription factors (transcription factor activity prediction). Additionally, drug sensitivity analysis and metabolic analysis were performed to reveal the effects of LRG on gemcitabine resistance and metabolic pathways. Finally, functional experiments were conducted by silencing the expression of LRG in PANC-1 and Bx-PC-3 cells to validate its influence to proliferation and invasiveness on PANC-1 and Bx-PC-3 cells. Through a series of algorithmic filters, we identified PAK2 as a key gene promoting pancreatic cancer liver metastasis. GSVA analysis elucidated the activation of the TGF-beta signaling pathway by PAK2 to promote the occurrence of liver metastasis. Pseudo-temporal analysis revealed a significant correlation between PAK2 expression and the lower differentiation status of pancreatic cancer cells. Cell communication analysis revealed that overexpression of PAK2 promotes communication between cancer cells and the tumor microenvironment. Transcription factor activity prediction displayed the transcription factor network regulated by PAK2. Drug sensitivity analysis and metabolic analysis revealed the impact of PAK2 on gemcitabine resistance and metabolic pathways. CCK8 experiments showed that silencing PAK2 led to a decrease in the proliferative capacity of pancreatic cancer cells and scratch experiments demonstrated that low expression of PAK2 decreased invasion capability in pancreatic cancer cells. Flow cytometry reveals that PAK2 significantly inhibited apoptosis in pancreatic cancer cell lines. Molecules related to the TGF-beta pathway decreased with the inhibition of PAK2, and there were corresponding significant changes in molecules associated with EMT. PAK2 facilitated the angiogenic potential of cancer cells and promotes the epithelial-mesenchymal transition process by activating the TGF-beta signaling pathway. Simultaneously, it decreased the differentiation level of cancer cells, consequently enhancing their malignancy. Additionally, PAK2 fostered communication between cancer cells and the tumor microenvironment, augments cancer cell chemoresistance, and modulates energy metabolism pathways. In summary, PAK2 emerged as a pivotal gene orchestrating pancreatic cancer liver metastasis. Intervening in the expression of PAK2 may offer a promising therapeutic strategy for preventing liver metastasis of pancreatic cancer and improving its prognosis.

ABLIM1, a novel ubiquitin E3 ligase, promotes growth and metastasis of colorectal cancer through targeting IĸBα ubiquitination and activating NF-ĸB signaling

Actin-binding LIM protein 1 (ABLIM1), a member of the LIM-domain protein family, has been reported as a suppressor in several tumors whereas its role in colorectal cancer (CRC) remains unknown. In this study, we find that ABLIM1 is up-regulated in CRC patients and high levels of ABLIM1 predict short disease-free survival time. Knock-down of ABLIM1 in CRC cell lines by lenti-virus leads to inhibited cell proliferation, migration, and invasion capabilities in vitro and impaired growth of tumor xenografts and liver metastasis lesions in vivo, while ABLIM1 overexpression accelerates tumor growth and invasion in vitro. Mechanistically, we uncover that ABLIM1 activates the NF-ĸB/CCL-20 signaling through modulating IĸBα ubiquitination and proteasomal-mediated degradation. Further co-immunoprecipitation, in vivo and in vitro ubiquitination assays reveal ABLIM1 as a novel ubiquitin E3 ligase binding to IĸBα. Interestingly, The E3 ligase catalysis activity of ABLIM1 depends on its 402–778aa rather than its LIM domains and its interaction with IĸBα relies on the HP domain. Our findings delineate the oncogenic role of ABLIM1 in CRC progression and reveal it as a novel E3 ligase targeting IĸBα, providing new insights into the regulation of NF-ĸB signaling in tumors.

Neural Wiskott-Aldrich syndrome protein (N-WASP) promotes distant metastasis in pancreatic ductal adenocarcinoma via activation of LOXL2.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive solid malignancies. A specific mechanism of its metastasis has not been established. In this study, we investigated whether Neural Wiskott-Aldrich syndrome protein (N-WASP) plays a role in distant metastasis of PDAC. We found that N-WASP is markedly expressed in clinical patients with PDAC. Clinical analysis showed a notably more distant metastatic pattern in the N-WASP-high group compared to the N-WASP-low group. N-WASP was noted to be a novel mediator of epithelial-mesenchymal transition (EMT) via gene expression profile studies. Knockdown of N-WASP in pancreatic cancer cells significantly inhibited cell invasion, migration, and EMT. We also observed positive association of lysyl oxidase-like 2 (LOXL2) and focal adhesion kinase (FAK) with the N-WASP-mediated response, wherein EMT and invadopodia function were modulated. Both N-WASP and LOXL2 depletion significantly reduced the incidence of liver and lung metastatic lesions in orthotopic mouse models of pancreatic cancer. These results elucidate a novel role for N-WASP signaling associated with LOXL2 in EMT and invadopodia function, with respect to regulation of intercellular communication in tumor cells for promoting pancreatic cancer metastasis. These findings may aid in the development of therapeutic strategies against pancreatic cancer.

Laser ablation in complex treatment of metastatic liver lesions

Laser ablation in complex treatment of metastatic liver lesions

Efficacy and Safety of Liver Chemoembolization Procedures, Combined with FOLFIRI Chemotherapy, in First-Line Treatment of Metastatic Colorectal Cancer in Patients with Oncogene Mutations.

The usual first- and second-line treatments for inoperable liver metastases from colorectal cancer (CRC) involve systemic chemotherapy, often with molecular targeted therapy. Chemoembolization, using microspheres loaded with irinotecan, has also been available as a treatment option for many years, used mainly in later lines of treatment when, due to increasing resistance, other chemotherapy regimens may have been exhausted. However, when there are contraindications to molecular therapies, the use of chemoembolization as first or second lines of treatment, in combination with FOLFIRI chemotherapy, may provide greater efficacy due to reduced irinotecan resistance. The aim of the study was to evaluate the efficacy and safety of transarterial chemoembolization (DEB-TACE) procedures for the treatment of metastatic liver lesions from CRC, using irinotecan-loaded microspheres as first-line treatment together with FOLFIRI chemotherapy. The analysis included 20 patients (12 females; 8 males) with unresectable liver metastases in the course of CRC with KRAS, NRAS and BRAF mutations, who underwent 73 chemoembolization procedures with microspheres loaded with 100 mg of irinotecan, in combination with interspersed FOLFIRI chemotherapy. Response to treatment was assessed through computed tomography according to the Modified Response Evaluation Criteria in Solid Tumors (mRECIST). Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method. Assessment of adverse events utilized the Cancer Therapy Evaluation Program's Common Terminology Criteria for Adverse Events (CTCAE; version 5.0). Partial remission (PR) was observed in 11 (55%) patients while 5 (25%) patients showed stable disease (SD). Progression (PD) was observed in 4 (20%) patients. Median PFS was 9.1 months (95% CI: 7.2-10.1 months) and median OS was 20.7 months (95% CI: 18.2-23.3 months). The most common adverse events (AEs) resulting in treatment delay were hematological disorders, notably neutropenia (CTCAE grades 1-3). No deaths or AEs above grade 3 occurred during TACE. Continued FOLFIRI chemotherapy after TACE treatments resulted in grade 4 neutropenia in two patients, grade 3 in four patients and grade 2 thrombocytopenia in two patients. Combining FOLFIRI chemotherapy with chemoembolization procedures for liver metastatic lesions from colorectal cancer may provide a valuable treatment option for patients not qualified for monoclonal antibody therapy.

Anti-Prokineticin1 Suppresses Liver Metastatic Tumors in a Mouse Model of Colorectal Cancer with Liver Metastasis.

Multidisciplinary treatment for colorectal cancer (CRC) has undergone significant advances, and molecularly targeted drugs have substantially improved patient prognosis. However, one problem with current molecularly targeted therapeutics is that they must be used in combination with anticancer agents. New molecular targeted therapies that can be used alone are needed. We have previously identified prokineticin1 (PROK1) factor as a therapeutic potential target for CRC. PROK1 factor is involved in the angiogenesis of tissues surrounding CRC tumors. Additionally, PROK1 receptors 1 and 2 are expressed in CRC cell lines, playing roles in cell proliferation via an autocrine mechanism and in the signaling system. In this study, a liver metastasis mouse model was developed using human colorectal cancer cell lines, and mice were divided into anti-PROK1 antibody administration and control groups. Mice were treated intraperitoneally with antibodies or phosphate-buffered saline (control) every three days. The number, size, and cell proliferation ability of metastatic lesions were analyzed. Our results suggested that the number, size, and cancer cell proliferation ability of metastatic lesions decreased, and the survival time significantly increased in the antibody-treated group compared to those in the control group. Thus, the anti-PROK1 antibody therapy suppressed the cell proliferation ability of liver metastatic lesions in a CRC mouse model, suggesting its potential as a novel treatment strategy.

SCGN and STAT3 expressions are associated with the prognosis of ccRCC

Clear cell renal cell carcinoma (ccRCC) is highly heterogeneous and accounts for about 70% of RCC. Its prognosis is worse than that of most histological types of RCC. In order to find potential biomarkers that may influence the prognosis and survival in ccRCC patients, we explored the expressions of STAT3, PDL1 and SCGN (secretagogin) in ccRCC based on the data of TCGA (n = 529), EMATAB-1980 (n = 99) and our own cohort (n = 99). Our study demonstrated that ccRCC patients with low STAT3 expression and high SCGN expression might have a better prognosis. No significant difference in the positive rate of SCGN expression was found when comparing the primary lesion with the matched metastatic liver lesions. The percentage of high SCGN expression in the primary lesion of metastatic ccRCC patients was significantly lower than that of patients with only the renal lesion. In view of the conclusion that STAT3 high expression cases are resistant to sunitinib, STAT3 immunohistochemistry results are essential for designing non-operative treatments. SCGN has the potential to become an indicator for subtype classification of ccRCC.

The Molecular, Immunologic, and Clinicodemographic Landscape of MYC-Amplified Advanced Prostate Cancer

BackgroundMYC is a commonly amplified, potentially targetable gene in prostate cancer (PCa). We sought to define the molecular, immunologic, and clinicodemographic landscape of MYC amplification (MYCamp) in advanced PCa to establish a rationale for personalized treatment combinations. MethodsHybrid capture-based comprehensive genomic profiling (CGP) was performed on PCa tumor samples. MYCamp = copy number ≥6 (CN). Patients treated between January 2011 and December 2020 were selected from a nationwide deidentified (280 clinics) EHR-derived clinicogenomic database (CGDB). ResultsOf 12,528 hormone-sensitive and castrate-resistant (CRPC) samples, MYCamp was detected in 10.6% (median CN = 8). MYCamp was more frequent in men with African versus European ancestry (12.9% vs. 10.2% P = .002), in metastatic vs. primary tissue (15.7% vs. 6.2% P < .001), and enriched in metastatic liver lesions (20.2%), but inversely associated with high microsatellite-instability (0.8% vs. 2.4%, P < .001). MYC CN≥15 was associated with PD-L1 expression (26.1% vs. 9.8%, P = .025). Amplification of AR, RAD21, LYN, CCND1, ZNF703, FGF3/4/19, and FGFR1 was enriched in MYCamp vs. MYCwt (all P < .001). In liquid samples with tumor fraction [TF]>0, MYCamp was detected in 2.0% (28/1,402), and 4.5% (20/445) with TF>20%. In the CGDB, (67 MYCamp and 658 MYCwt), patients received similar treatments; most received hormone therapies (35.8% MYCamp vs. 31.5% MYCwt) or chemotherapy (37.3% MYCamp vs. 27.7% MYCwt) as first therapy after CGP report. ConclusionMYCamp defines a biologically distinct subset of PCa patients and is characterized with multiple proxies of advanced disease. These data suggest that MYCamp may be prognostic; independent cohorts are needed to validate these findings.

Local Control Following Stereotactic Body Radiation Therapy for Liver Oligometastases: Lessons from a Quarter Century.

The utilization of stereotactic body radiation therapy for the treatment of liver metastasis has been widely studied and has demonstrated favorable local control outcomes. However, several predictive factors play a crucial role in the efficacy of stereotactic body radiation therapy, such as the number and size (volume) of metastatic liver lesions, the primary tumor site (histology), molecular biomarkers (e.g., KRAS and TP53 mutation), the use of systemic therapy prior to SBRT, the radiation dose, and the use of advanced technology and organ motion management during SBRT. These prognostic factors need to be considered when clinical trials are designed to evaluate the efficacy of SBRT for liver metastases.

THU527 Metastatic Adenocarcinoma Of The Colon Concealing An ACTH Secreting Neuroendocrine Differentiated Cluster: A Lethal Zebra Within A Trojan Horse

Abstract Disclosure: M. Velasquez: None. S. Shekhar: None. R.M. Goyal: None. Background: Ectopic ACTH secreting tumors are responsible for almost 10% of all cases of Cushing Syndrome. Tumors associated with this entity are most commonly small cell lung, thymic, and pancreatic neuroendocrine tumors. Few cases of colon adenocarcinoma with paraneoplastic ACTH secretion have been reported. They are associated with poor outcomes. Clinical case: A 57-year-old previously healthy male presented with shortness of breath and hypertension. CTA of the chest revealed metastatic liver lesions. CT abdomen and pelvis confirmed metastatic liver lesions with an apple core colonic mass consistent with a primary malignancy. Liver biopsy showed well-differentiated neuroendocrine tumor; tumor cells were negative for CK20, chromogranin, and CD56 but positive for CK7 and synaptophysin. The Ki-67 index was 30%. He was not evaluated for paraneoplastic hormonal secretion and the colonic mass wasn’t biopsied at that time. Ga-DOTATATE scan was negative for somatostatin uptake. He was started on carboplatin-etoposide + dexamethasone (three doses of 4mg each). Two months later presented with large bowel obstruction. Colonoscopy was performed and histopathology demonstrated colonic adenocarcinoma with focal neuroendocrine differentiation with positive CDX2 and negative CK7 and CK20. Synaptophysin was diffusely positive with sparse chromogranin positivity. ACTH stain of the colonic biopsy was negative. Chemotherapy was switched to FOLFORINOX and dexamethasone (one dose of 12mg). After two weeks of being on this regimen, he developed refractory hypokalemia and metabolic alkalosis and was sent to the emergency department. Vitals signs were within normal limits except for mildly elevated blood pressure. Physical examination remarkable for redness of his truncal skin. He did have changes in his handwriting, 0/3 three-word recall, and reduced short term memory. Primary team performed a morning cortisol that was elevated, and endocrinology was consulted. Two repeated 8AM cortisol level and a serum ACTH were found to be elevated. An 8mg overnight dexamethasone suppression test revealed an increase in cortisol. MRI brain showed no evidence of intracranial abnormalities. Refractory hypokalemia due to ectopic ACTH-dependent Cushing syndrome was diagnosed warranting treatment with ketoconazole. Unfortunately, he developed septic shock which led to his demise. Conclusion: This case illustrates a paradoxical rise in serum cortisol levels after dexamethasone suppression test suggesting the presence of positive feedback effects of exogenous corticosteroids on tumor’s ACTH release/production. Recognition of this syndrome is critical to avoid unnecessary use of exogenous glucocorticoids since they could trigger paraneoplastic Cushing syndrome in these patients. Presentation: Thursday, June 15, 2023

SAT154 Insulin Autoimmune Syndrome In The Setting Of Metastatic Colon Cancer: Case Report

Abstract Disclosure: M. Bernal: None. J. Suarez: None. K.M. Tuna: None. F. Amer: None. M. Lamas: None. Insulin Autoinmune Syndrome is a rare cause of hypoglycemia. Its incidence is higher among Asians, Japanese patients. Also known as Hirata’s disease, it is characterized by the presence of a hyperinsulinemic state, hypoglycemia, elevated insulin antibodies titers without prior exposure to exogenous insulin, and no pathological abnormalities of the pancreatic islets cells. Some commonly used drugs and viruses have been identified as triggers. We present the case of 65-year-old male Caucasian patient who presented with recurrent episodes of hypoglycemia, that started after surgical resection of a metastatic liver lesion, in the context of metastatic colon cancer. During the workup, it was confirmed that patient had hyperinsulinemia, hypoglycemia, and positive auto-insulin antibodies without previous exposure to exogenous insulin and no imaging findings suggestive of a pancreatic abnormality. The relevance of this case is not only related to the rarity of this entity in the Western World, but also the possibility of being associated with a paraneoplastic syndrome in the setting of metastatic colon cancer, which to the best our knowledge, has not yet been described in the literature as a possible trigger of Insulin Autoimmune Syndrome. Presentation: Saturday, June 17, 2023

MRI Guided Adaptive Radiotherapy (MRgART) in Primary and Metastatic Liver Lesions

The role of stereotactic body radiotherapy (SBRT) in the management of primary hepatic and metastatic tumors has increased significantly over the past few years. MR-Linac is rapidly gaining evidence in the delivery of ablative doses using MR guided adaptive radiotherapy (MRgART) with improved accuracy and dose coverage to the lesions. We report local control and toxicity of patients with primary and metastatic liver lesions treated with MR guided adaptive SBRT. All patients were treated with MRgART on the Unity 1.5T MR Linacs at two institutions and consented to the ADAPT-MRL study (1). A 4DCT and MRI with abdominal compression were obtained at simulation and the primary MRI sequence used for online treatment included a T2 3D navigated scan. A balanced turbo field echo (btFFE) 2D cine motion scan was also acquired at every fraction to determine movement of the tumor to aid in internal target volume margin. All plans were treated with SBRT prescribed to 3-5 alternate daily fractions. Acute toxicity was reported according to Common Terminology Criteria for Adverse Events version 5 (CTCAE) v.5. Patient demographics, prescribed dose fractionation, acute toxicity and clinical response at 6 months were analyzed. Clinical response to treatment was measured according to RECIST criteria 1.1. Between February 2021 to January 2023 a total of 30 patients were treated with 149 fractions to the liver. Patients were majority male (70%) with a median age of 66 (range 36-83). 16 patients were treated for primary hepatocellular carcinoma (HCC) of the liver and 14 patients for metastatic liver lesions. The median prescribed dose was 48 Gy (range 30-50Gy) in median 5 fractions (range (3-5 fractions). All patients completed treatment with no interruptions. The mean time from 'patient setup' to 'beam-off' was 52.6 minutes (range 37-73 minutes). Data on acute toxicity at 3 month follow up was available for 28 patients. Of these patients 7/28 (25%) had grade 1 or 2 toxicity and no >/ = grade 3 toxicity was reported. Clinical response at 6 months was available for 18 patients and showed complete response in 44% (8/18), partial response in 22% (4/18), stable disease in 22% (4/18) and progressive disease in 11.1% (2/18). Our experience on MRgART to the liver has shown good local control and minimal acute toxicity in the treatment of primary and metastatic liver lesions. We continue to collect data on patient reported outcomes, clinical response and toxicity to determine the feasibility and safety of this system.

Long-Term Survival Outcome for Metastatic Nasopharyngeal Carcinoma Patients Receiving Radiation to Primary and Metastatic Sites with Palliative Chemotherapy

A total of 6% - 8% of NPC patients were initial diagnosed as distant metastatic disease. The median overall survival (OS) is only 10-15 months with palliative chemotherapy for these patients. A phase III study showed that palliative chemotherapy combined with radical radiotherapy to primary site could be a newly effective treatment method for metastatic NPC. Another phase 2, RCT found that the patients who had the solid tumors with 1-5 metastases received standard palliative care plus stereotactic body radiation therapy (SABR), and the 5-year OS were improved to 42.3%. Nevertheless, there was few studies focus on the radiation to both primary site and metastatic lesions. Therefore, we aimed to investigate the potential clinical benefits for initial diagnosed metastatic NPC patients with radiation to both primary site and distant metastatic lesions plus palliative chemotherapy. Metastatic NPC patients treated with radiation to both primary site and distant metastatic lesions plus palliative chemotherapy were retrospectively collected in our hospital from May 2008 to May 2022. For treatment group, all patients underwent IGRT according to ICRU reports 50 and 62. The prescribed dose for primary site: GTVT: ≥66Gy, GTVn: ≥66Gy, CTV1: 60-66Gy, CTV2 54-60Gy, CTVln 50-54Gy. And the prescribed dose for distant metastatic lesions was more than 30Gy. For the control group, the patients treated with palliative chemotherapy were selected by propensity score matching from our hospital. The regimen for palliative chemotherapy was cisplatin-based chemotherapy every three weeks (100mg/m2 D1) for both groups. Kaplan-Meier method was used to analyze the OS. Cox regression model was used for multivariate analysis. A total of 54 metastatic NPC patients with radiation to both primary site and distant metastatic lesions were retrospectively included in the treatment group, and another 54 patients were selected as the control group. The median follow-up time was 52 months. In the treatment group, the median age was 52 years (37-82), male (68%), female (32%), the main metastatic sites were bone (36 cases, 66%), lung (18 cases, 33%) and liver (10 cases, 18%). There were 23 oligometastasis cases and 31 cases. 3-year and 5-year OS in the treatment group were both dramatically improved than control group (63.2% vs 50.6%, p<0.05; 49.6% vs 38.9%, p<0.05). Multivariate analysis showed that T stage, liver metastatic lesion and oligometastases were the independent prognostic factors for them. Palliative chemotherapy combined with radiation to primary sites and distant metastatic lesions might improve the OS for initial diagnosed distant metastatic NPC patients. More prospective clinical trials were needed to confirm it further.

Pancreatic Cancer Outcome: Local Treatment with Radiation Using MRI-Linac

Stereotactic MR-guided on-table adaptive radiotherapy (SMART) is a surging modality in radiotherapy, delivering high dose radiation to the tumor in great proximity to susceptible organs. The aim of this study is to evaluate the clinical outcome in locally advanced or recurrent pancreatic tumors with or without prior irradiation. All consecutive patients were treated in our center for pancreatic cancer (PC) using SMART technology to a prescription of 50Gy (BED10 100 Gy1o) in 5 fractions, with daily on-table adaptation of treatment plan. Endpoints for this retrospective, single center, IRB approved study were local control, overall survival, local disease-free period, acute and late toxicities. Fifty-four PC patients were treated between 8.2019-9.2022, with median follow-up of 8.9 months from SMART (0.8-34 months). Forty patients had upfront inoperable PC (45% were metastatic at RT, five treated to liver metastatic lesions concomitantly) and fourteen patients had local recurrence following prior pancreatectomy, six of them had prior adjuvant RT. 87% received at least one round of chemotherapy (Oxaliplatin based- 72%), 25% received ≥2 regimens. Mean age was 68.9 (45-86) years. There was no significant difference in baseline parameters between prior pancreatectomy and inoperable groups. On-table adaptive replanning was performed for 100% of all (269) fractions (one patient received 4 fractions). No patient reported grade ≥2 acute GI toxicity. Six patients reported fatigue at the end of RT, four of them had prior radiation. Forty-eight patients were available for evaluation. Complete local control was achieved in 21.7% (10 patients) for median of 9 months (2.8-28.8 months), three had later local progression. Eight patients had regional or marginal recurrence following treatment. 6-months and 12-months OS was 75% and 52%, respectively. There was no significant difference in toxicity and outcome between post-pancreatectomy and inoperable groups. Pancreatic cancer local ablative SMART is safe, with minimal treatment-related toxicity, even in previously irradiated patients. Local control with complete response was achieved by 20% of patients. Further studies are needed to evaluate long-term outcome and late toxicity.

Exploring the Role of MRI in the Detection of Atypical Liver Hemangiomas and Exclusion of Metastases

Background: In this article, we highlight the importance of utilizing multiple imaging modalities, including CT, MRI, and abdominal Doppler ultrasound, to accurately differentiate between atypical liver hemangiomas (LH) and metastases. Case report: We introduce a 57-year-old male patient who presented with severe abdominal pain. Initial CT scan findings showed hypodense liver lesions and a well-defined hypodense mass in the sub-diaphragmatic region, raising suspicion for metastatic liver lesions, and prompting further evaluation. To differentiate between atypical hemangiomas and metastases, an MRI scan was performed, revealing a hyperintense signal on T2-weighted images and a hypointense signal on T1-weighted images, consistent with the characteristics of LH. These characteristic signal intensities aided in ruling out metastatic liver lesions, which typically present with a more solid and homogeneous appearance. Contrast-enhanced MRI played a crucial role in confirming the diagnosis. The liver lesions demonstrated moderate vascularization during the early phase of contrast enhancement, followed by progressive centripetal filling during the portal venous and delayed phases. This enhancement pattern is consistent with the slow flow within the dilated vascular spaces of liver hemangiomas. The lesion in the right liver lobe is almost completely filled with contrast, further supporting the diagnosis of hemangioma. Abdominal Doppler ultrasound can provide additional information regarding the vascularity of liver lesions. In this case, the Doppler examination likely helped to further confirm the presence of a hemangioma, as these lesions typically demonstrate increased vascularity compared to metastatic lesions. Conclusion: The comprehensive imaging evaluation utilizing CT, MRI, and abdominal Doppler ultrasound allowed for the confident differentiation of atypical liver hemangiomas from metastatic liver lesions in this case. This emphasizes the importance of a multimodal imaging approach in cases of liver lesions with overlapping features, leading to improved patient management and outcomes.

Risk and prognostic factors in patients with colon cancer with liver metastasis.

The most common site of metastasis in patients with colon cancer is the liver. This study aimed to identify patients with colon cancer at high risk of developing liver metastasis and to explore their prognosis. The clinical characteristics, treatment methods and survival outcomes of patients diagnosed with colon cancer from 2010 to 2015 were identified from the Surveillance, Epidemiology and End Results (SEER) database. Patients were divided into two groups according to the presence of liver metastasis, and multivariate logistic and Cox regression models were used to identify risk and prognostic factors. A total of 60,018 patients with colon cancer were selected from the SEER database. The incidence of liver metastasis was 9.2%. African American ethnicity, poor differentiation, higher tumor stage, higher lymph node ratio, and lung metastases were common factors associated with both liver metastasis risk and prognosis. Metastasectomy might improve survival among patients with colon cancer with resectable liver metastasis lesions and no other organ involvement.

Diagnostic value of 18F-FDG PET/CT and 68Ga-FAPI PET/CT in primary liver cancer: A systematic review and meta-analysis.

To conduct a meta-analysis of the diagnostic efficacy of fluorine-18-fluorodeoxyglucose (18F-FDG) and gallium-68-labeled fibroblast-activation protein inhibitor (68Ga-FAPI) positron emission tomography/computed tomography (PET/CT) for primary liver cancer based on existing clinical evidence. Meta-analysis was carried out according to PRISMA reporting specification. The clinical studies in PubMed/Medline, Embase and the Cochrane Library database were retrieved from the establishment to September 2022. Two researchers independently conducted literature screening and data extraction, evaluated the risk of bias according to QUADAS-2, conducted meta-analysis using Meta Disc 1.4 and Stata15.1 software, and calculated the summarized sensitivity (SEN), specificity (SPE), positive likelihood ratio (+LR), negative likelihood ratio (-LR), and diagnostic odds ratio (DOR). The diagnostic performance of 18F-FDG PET/CT and 68Ga-FAPI PET/CT for primary liver cancer was compared using summarized receiver operating characteristic (SROC) curve and area under curve (AUC). Four original studies on 18F-FDG PET/CT and 68Ga-FAPI PET/CT in the diagnosis of primary liver cancer were included, including 159 intrahepatic lesions in 106 patients. Taking lesions as a unit, in four original studies, the pooled results of 18F-FDG PET/CT diagnosis of primary liver cancer were Sen=0.5 (95% CI:95% CI: 0.41-0.59), Spe=0.87 (95% CI: 0.52-0.98), AUC=0.58 (95% CI:0.53-0.62); The pooled results of 68Ga-FAPI PET/CT in the diagnosis of primary liver cancer, Sen=0.5 (95% CI: 0.41-0.59), Spe=0.87 (95%CI:0.52-0.98), AUC=0.58 (95% CI:0.53-0.62). Besides, the Sen of 68Ga-FAPI PET/CT in the diagnosis of primary liver cancer was higher than that of 18F-FDG PET/CT (Z=2.323, P=0.02), the difference was statistically significant. Gallium-68-FAPI PET/CT is a promising tool. Compared with 18F-FDG, 68Ga-FAPI has higher sensitivity to detect more lesions in primary liver cancer and metastatic lesions, and has high performance in the diagnosis of primary liver cancer.