Diagnosis Of Liver Metastases Research Articles

Size selection of intrahepatic lesions for cryoablation contributes to abscopal effect and long-term survival in patients with liver metastatic melanoma receiving PD-1 blockade therapy

ObjectivesIn this study, we aimed to examine parameters of cryoablation, tumor characteristics, and their correlations with distant tumor response and survival of liver metastatic melanoma patients receiving cryoablation and PD-1 blockade (cryo-PD-1) combination treatment.Materials and methodsA retrospective study was conducted among 45 melanoma patients who received combined PD-1 blockade therapy and cryoablation for liver metastasis from 2018 to 2022. Cox regression was utilized to determine the associations between factors and overall survival (OS). Changes in cytokines and immune cell compositions in peripheral blood samples following the combined treatment were investigated, along with their correlations with treatment response.ResultsThe mean cycle of cryo-PD-1 combination treatment was 2.2 (range, 1–6), and the 3-month overall response rate (RECIST 1.1 criteria) was 26.7%. Of the 21 patients who failed previous PD-1 blockade therapy after diagnosis of liver metastasis, 4 (19.0%) achieved response within 3 months since combination treatment. The diameter of ablated lesion ≤ 30 mm, metastatic organs ≤ 2, and pre-treatment LDH level ≤ 300 U/L were independent prognostic factors for favorable OS. Further analysis showed patients with intrahepatic tumor size of 15–45 mm, and ablated lesion size of ≤ 30 mm had significantly higher 3-month response rate (42.9% vs 12.5%; P = 0.022) and survival time (30.5 vs 14.2 months; P = 0.045) than their counterparts. The average increase in NLR among patients with ablated tumor size of ≤ 3 cm and > 3 cm were 3.59 ± 5.01 and 7.21 ± 12.57, respectively. The average increase in serum IL-6 levels among patients with ablated tumor size of ≤ 3 cm and > 3 cm were 8.62 ± 7.95 pg/ml and 15.40 ± 11.43 pg/ml, respectively.ConclusionSize selection of intrahepatic lesions for cryoablation is important in order to achieve abscopal effect and long-term survival among patients with liver metastatic melanoma receiving PD-1 blockade therapy.

Radiological complete response with regorafenib for multiple lung metastases of ascending colon cancer: a case report

BackgroundRegorafenib is an oral diphenylurea multikinase inhibitor and currently approved for use following third-line therapy for metastatic colorectal cancer (CRC) patients. Only one case has previously been reported of metastatic CRC showing a complete response (CR) to regorafenib.Case presentationA 68-year-old Japanese man underwent laparoscopy-assisted ileocecal resection and D3 lymphadenectomy due to his ascending colon cancer. Eighteen months after surgery, a laparoscopic hepatic left lateral segmentectomy was performed due to a liver tumor, and a pathological diagnosis of colorectal liver metastasis was made. Three months after the second surgery, contrast-enhanced computed tomography (CT) revealed multiple lung metastases. The patient had undergone 18 courses of the FOLFOX + bevacizumab chemotherapy regimen as their first-line therapy and 11 courses of the FOLFIRI + ramucirumab chemotherapy regimen as their second-line therapy. As their third-line therapy, the patient was administered the regorafenib chemotherapy regimen. We evaluated the chemotherapy treatment’s effect on the lung tumors by CT after 3, 7, 11, and 17 courses of the regorafenib chemotherapy regimen, finding that the lung tumors had shrunk with time; thus, each tumor was considered a partial response (PR) based on the RECIST guidelines. After 21 courses of the regorafenib chemotherapy regimen, the chemotherapy was discontinued in response to the patient’s wishes. Even at 1 and 3 months after the discontinuation of the chemotherapy, CT revealed that the lung tumors had shrunk, with each considered a PR. Furthermore, 9 months after the discontinuation of the chemotherapy, CT revealed scarring of the lung tumors. This was considered a CR, rather than a PR. The patient remains disease-free 18 months after the discontinuation of chemotherapy.ConclusionsIn this paper, we present the second case of radiological CR with regorafenib for multiple lung metastases of ascending colon cancer. Currently, there is no consensus on a treatment strategy for patients with radiological CR.

Trends in Selective Internal Radiation Therapy (SIRT) for Treating Hepatocellular Carcinoma, Cholangiocarcinoma, and Liver Metastasis: A Total Population Analysis from 2006 to 2021 in Germany.

The aim of this study was to investigate trends in selective internal radiation therapy (SIRT) for hepatocellular carcinoma (HCC), cholangiocarcinoma (CCC), and liver metastasis in Germany. We analyzed the nationwide German hospital billing database from 2006 to 2019 for the diagnosis of HCC, CCC or liver metastasis in combination with SIRT. For analyses of SIRT on the hospital level, we used the reimbursement.INFO tool based on German hospitals' quality reports from 2008 to 2021. Linear regression analysis was performed to detect changes over time. We included a total of 14,165 SIRT procedures. The annual numbers increased from 99 in 2006 to 1605 in 2015 (p < 0.001; increase by 1521%), decreasing to 1175 cases in 2019 (p < 0.001). In 2008, 6 of 21 hospitals (28.6%) performed more than 20 SIRTs per year, which increased to 19 of 53 (35.8%) in 2021. The share of SIRT for HCC increased from 29.8% in 2006 to 44.7% in 2019 (p < 0.001) and for CCC from 0% in 2006 to 9.5% in 2019 (p < 0.001), while the share of SIRT for liver metastasis decreased from 70.2% in 2006 to 45.7% in 2019 (p < 0.001). In-hospital mortality was 0.2% after the SIRT procedure. Gastritis (2.7%), liver failure (0.4%), and sepsis (0.3%) were the most common in-hospital complications reported. We observed an increase in SIRT procedures in Germany, with the number of hospitals offering the procedure going up from 21 in 2008 to 53 in 2021. While the treatment of liver metastasis remains the most common indication, SIRT for HCC and CCC increased significantly over the last few years. The mortality and complication rates show that SIRT is a relatively safe procedure.

Whole Liver Radiotherapy for Multiple Liver Metastases in Thoracic Malignancies

Liver metastases (LM) are common in advanced thoracic cancer patients with dismal oncological outcomes. Even in the modern era of novel systemic therapy, LM led to a 21% increased mortality risk compared with those without. Options for progressive multiple LM after systemic therapy are limited. Therefore, a different treatment modality is urgently needed to overcome such a predicament. Herein, we renovate the classical whole liver radiotherapy (WLRT) and evaluate its efficacy and safety in treating thoracic cancer patients with progressive multiple LM. Patients with lung or thymic cancer who had multiple LM treated by WLRT between 2018 and 2022 were enrolled. Radiotherapy (RT) was delivered with a median dose of 24 Gy (range 8-25 Gy) in 8 fractions (range 1-16) at the discretion of treating physicians. Overall survival (OS) and cumulative incidence of intrahepatic progression were calculated from the completion of WLRT till death or progression by Kaplan-Meier and competing risk analyses, respectively. Twenty-four patients were enrolled in this retrospective study. Eleven patients (46%) had lung adenocarcinoma, of which nine patients had oncogenic mutations. Six patients (25%) had small cell lung cancer (SCLC), four patients (17%) had thymic squamous cell carcinoma (SqCC), two patients (8%) had lung SqCC, and one patient (4%) had mixed histology. Eighteen patients (75%) were under systemic therapy treatment before the diagnosis of LM, and fifteen (63%) received LM biopsy. The median time from the diagnosis of LM to WLRT was 7.5 months (range, 0.5-33.9 months). Eleven patients (46%) had concurrent RT and systemic therapy. With a median follow-up of 3.1 months, the 3-, 6- and 12-month OS were 57%, 38%, and 15%, respectively. After adjusting death as a competing risk, the cumulative incidence of LM progression at 3, 6, and 12 months were 10%, 19%, and 44%, respectively. Within three months after the completion of RT, one patient (4%) had grade 5 radiation-induced liver disease (RILD), one patient (4%) had grade 4 abnormal liver function test (LFT), three patients (13%) had grade 3 abnormal LFT, and twelve patients (50%) had ≤ grade 2 abnormal LFT. The patient who had Gr.5 RILD expired 51 days after the completion of RT with 24 Gy in 8 fractions concurrently with topotecan. He had primary SCLC with viral hepatitis B. His LFT was around the normal upper limit before WLRT. WLRT provided favorable intrahepatic control with acceptable radiation-related toxicities and could be considered a treatment option for patients with progressive LM under systemic therapy. Further investigation with a larger cohort is warranted to identify patients at a high risk of developing severe RILD.

Phase 1 Trial of SPECT-Guided Liver-Directed Ablative Radiotherapy for Patients with Low Functional Liver Volume

Traditional liver dose constraints specify that a critical volume of 700 cc of non-tumor liver should be spared from receiving a hepatotoxic dose. We evaluated the safety of liver-directed ablative radiotherapy for patients with hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (iCCA), or liver metastases (LM) with Child-Pugh (CP) A5 liver function at baseline and with low functional liver volume as estimated by Tc-99m sulfur colloid single photon emission computed tomography (SPECT). We hypothesized that functional liver image guidance with SPECT would allow safe delivery of ablative radiotherapy in patients with limited liver volume. A phase 1 trial with a 3+3 design was conducted to evaluate the safety of comprehensive ablative radiotherapy to the liver disease using escalating functional non-target liver radiation dose constraints. Eligibility criteria included (1) a diagnosis of HCC, iCCA, or LM, (2) prior treatment with irinotecan or oxaliplatin chemotherapy or liver resection, and (3) a minimum functional liver volume of 400 cc as estimated by SPECT using a threshold of 40% maximum intensity. Patients with CP >A5 liver function, prior liver-directed radiotherapy, or prior Yttrium-90 therapy were excluded. The prescription dose was 67.5-75 Gy in 15 fractions or 75-100 Gy in 25 fractions. The volumetric dose constraint for functional non-target liver receiving <24 Gy for 15 fractions or <27 Gy for 25 fractions was determined by the dose level of trial enrollment: level 0 was ≥400 cc and level +1 was ≥300 cc. A level -1 was included if needed. We used standard 15 and 25 fraction dose constraints for other organs at risk. The following dose limiting toxicities (DLTs) were assessed within 6-8 weeks of completing radiotherapy: Grade 3 hypoalbuminemia, increase in INR, increase in bilirubin, or ascites, or Grade 4 hepatic failure or any radiation-related toxicity. Twelve patients enrolled between February 2016 and June 2022. The median (range) GTV was 36 (2-651) cc. The median CT anatomical non-tumor liver volume was 1584 (764-2699) cc, and the median SPECT functional liver volume was 1117 (570-1928) cc, with a Pearson correlation coefficient of 0.98 (p<0.001). The median non-target SPECT functional liver volume below the volumetric dose constraint was 684 (429-1244) cc. None of the 3 patients treated in dose level 0, and none of the 9 patients treated in dose level +1 experienced any DLTs. The 1-year in-treatment-field control rate was 55%, and 1-year overall survival was 71%. Ablative radiotherapy can be safely delivered using functional SPECT image guidance, which enables sparing lower volumes of functional liver than traditionally accepted in patients with CP A5 liver function. Further evaluation with a phase 2 study is warranted.

Probe-based confocal laser endomicroscopy for real-time evaluation of colorectal liver metastasis in resected surgical specimens

Probe-based confocal laser endomicroscopy (pCLE) enables real-time examination of tissue structure. This study investigated pCLE with or without fluorescein sodium for the intraoperative diagnosis of colorectal liver metastasis (CLM) and detection of surgical margins. Thirty-four specimens of CLM and adjacent noncancerous tissue were obtained from 21 patients and examined by pCLE between May 2017 and March 2018. Images were obtained both without and with fluorescein sodium applied to the cut surface and compared with hematoxylin and eosin-stained tissue. Fluorescence intensity (FI) was measured by luminance-analysis software. Without external fluorophores, pCLE visualized 91.2% of CLM tissues as an irregular structure with low autofluorescence and 90.5% of noncancerous liver tissues as a regular structure with high autofluorescence. The median FI was significantly lower in cancer than in benign tissue in patients without chemotherapy [70.4 (51.6–110) vs. 48.3 (39.0–59.4), p = 0.002] and with chemotherapy [67.9 (54.6–89.2) vs. 48.6 (28.8–82.1), p < 0.001]. The border was clearly visible; pCLE with fluorescein sodium clearly showed their morphologies. In summary, our study demonstrated real-time pCLE distinguished CLM and noncancerous tissue by differences in structure and FI regardless of prehepatectomy chemotherapy. Fluorescein spray facilitated clear visualization of differences in the morphology.

A case in which ultrasound-guided fine needle aspiration was useful in the diagnosis of liver metastasis of gallbladder cancer

A case in which ultrasound-guided fine needle aspiration was useful in the diagnosis of liver metastasis of gallbladder cancer

Two machine learning-based nomogram to predict risk and prognostic factors for liver metastasis from pancreatic neuroendocrine tumors: a multicenter study

BackgroundPancreatic neuroendocrine tumors (PNETs) are one of the most common endocrine tumors, and liver metastasis (LMs) are the most common location of metastasis from PNETS; However, there is no valid nomogram to predict the diagnosis and prognosis of liver metastasis (LMs) from PNETs. Therefore, we aimed to develop a valid predictive model to aid physicians in making better clinical decisions.MethodsWe screened patients in the Surveillance, Epidemiology, and End Results (SEER) database from 2010–2016. Feature selection was performed by machine learning algorithms and then models were constructed. Two nomograms were constructed based on the feature selection algorithm to predict the prognosis and risk of LMs from PNETs. We then used the area under the curve (AUC), receiver operating characteristic (ROC) curve, calibration plot and consistency index (C-index) to evaluate the discrimination and accuracy of the nomograms. Kaplan-Meier (K-M) survival curves and decision curve analysis (DCA) were also used further to validate the clinical efficacy of the nomograms. In the external validation set, the same validation is performed.ResultsOf the 1998 patients screened from the SEER database with a pathological diagnosis of PNET, 343 (17.2%) had LMs at the time of diagnosis. The independent risk factors for the occurrence of LMs in PNET patients included histological grade, N stage, surgery, chemotherapy, tumor size and bone metastasis. According to Cox regression analysis, we found that histological subtype, histological grade, surgery, age, and brain metastasis were independent prognostic factors for PNET patients with LMs. Based on these factors, the two nomograms demonstrated good performance in model evaluation.ConclusionWe developed two clinically significant predictive models to aid physicians in personalized clinical decision-makings.

Hepatectomy Before Primary Tumor Resection as Preferred Approach for Synchronous Liver Metastases from Rectal Cancer.

For patients with synchronous liver metastases (LM) from rectal cancer, a consensus on surgical sequencing is lacking. We compared outcomes between the reverse (hepatectomy first), classic (primary tumor resection first), and combined (simultaneous hepatectomy and primary tumor resection) approaches. A prospectively maintained database was queried for patients with rectal cancer LM diagnosed before primary tumor resection who underwent hepatectomy for LM from January 2004 to April 2021. Clinicopathological factors and survival were compared between the three approaches. Among 274 patients, 141 (51%) underwent the reverse approach; 73 (27%), the classic approach; and 60 (22%), the combined approach. Higher carcinoembryonic antigen level at LM diagnosis and higher number of LM were associated with the reverse approach. Combined approach patients had smaller tumors and underwent less complex hepatectomies. More than eight cycles of pre-hepatectomy chemotherapy and maximum diameter of LM > 5 cm were independently associated with worse overall survival (OS) (p = 0.002 and 0.027, respectively). Although 35% of reverse-approach patients did not undergo primary tumor resection, OS did not differ between groups. Additionally, 82% of incomplete reverse-approach patients ultimately did not require diversion during follow-up. RAS/TP53 co-mutation was independently associated with lack of primary resection with the reverse approach (odds ratio: 0.16, 95% CI 0.038-0.64, p = 0.010). The reverse approach results in survival similar to that of combined and classic approaches and may obviate primary rectal tumor resections and diversions. RAS/TP53 co-mutation is associated with a lower rate of completion of the reverse approach.

Platinum-based chemotherapy in patients with castration-resistant prostate cancer and hepatic metastases.

e17063 Background: Patients with metastatic castration-resistant prostate cancer (mCRPC) and hepatic metastases face a dismal prognosis. In fact, the majority of phase 3 trials show no benefit of novel treatment modalities including Lutetium PSMA radioligand therapy (LuPSMA-RLT) in comparison with standard therapies for the subgroup of visceral metastases. In aggressive variant prostate cancer, the addition of platinum resulted in a clinically relevant improvement of progression free survival (PFS) and overall survival (OS). Whether adding platinum is also beneficial in unselected mCRPC patients with hepatic metastasis is unclear. Methods: We retrospectively analyzed mCRPC patients diagnosed with hepatic metastasis and treated with platinum-based chemotherapy or LuPSMA-RLT in three German centers (Hamburg, Essen, Munich). Patients with pure neuroendocrine prostate cancer were excluded. Survival rates and 95% confidence intervals (CI) were compared using the Kaplan Meier method and the logRank test. Results: A total of 84 mCRPC patients with hepatic metastasis who had received at least one platinum-based therapy and 32 patients treated with LuPSMA-RLT were evaluated. Median age at treatment initiation was 67 and 73 years. Patients had undergone a median of three treatment lines (83% ≥ 1 new hormonal agent (NHA); 87% ≥ 1 taxane based chemotherapy) before initiation of platinum based chemotherapy and a median of 4 treatment lines before LuPSMA-RLT. Median time to initiation of 1st platinum-based chemotherapy after diagnosis of liver metastases was 55 days. In total, 37% received carboplatin/cabazitaxel, 26% cisplatin or carboplatin/ etoposide, 11% carboplatin/docetaxel, and 26% other platinum-based combination therapies. In the platinum-treated group, 52.6% and 27% of the patients did not show progression at 3 and 6 months after treatment initiation as compared to 44.1% and 19.3% of the patients who received LuPSMA-RLT with a median PFS of 3.1 and 2.4 months, respectively. At 6 months 71.3% of the platinum-treated patients and 56.6% of the LuPSMA-RLT were alive. Overall, BRCA1/2 status was available for 53 of the platinum-treated patients, 15% of whom had a pathogenic alteration in either gene. This small subgroup was found to have a similar OS compared to the overall cohort. Conclusions: Platinum-based chemotherapy showed promising activity in mCRPC patients with hepatic metastasis. Given the high unmet medical need, platinum-based combination therapies should be further evaluated prospectively. [Table: see text]

Identifying liver metastasis-related hub genes in breast cancer and characterizing SPARCL1 as a potential prognostic biomarker.

The liver is the third most common metastatic site for advanced breast cancer (BC), and liver metastases predict poor prognoses. However, the characteristic biomarkers of BC liver metastases and the biological role of secreted protein acidic and rich in cysteine-like 1 (SPARCL1) in BC remain unclear. The present study aimed to identify potential biomarkers for liver metastasis of BC and to investigate the effect of SPARCL1 on BC. The publicly available GSE124648 dataset was used to identify differentially expressed genes (DEGs) between BC and liver metastases. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted to annotate these DEGs and understand the biological functions in which they are involved. A protein-protein interaction (PPI) network was constructed to identify metastasis-related hub genes and further validated in a second independent dataset (GSE58708). Clinicopathological correlation of hub gene expression in patients with BC was determined. Gene set enrichment analysis (GSEA) was performed to explore DEG-related signaling pathways. SPARCL1 expression in BC tissues and cell lines was verified by RT-qPCR. Further in vitro experiments were performed to investigate the biological functions of SPARCL1 in BC cells. We identified 332 liver metastasis-related DEGs from GSE124648 and 30 hub genes, including SPARCL1, from the PPI network. GO and KEGG enrichment analyses of liver-metastasis-related DEGs revealed several enriched terms associated with the extracellular matrix and pathways in cancer. Clinicopathological correlation analysis of SPARCL1 revealed that its expression in BC was associated with age, TNM stage, estrogen receptor status, progesterone receptor status, histological type, molecular type, and living status of patients. GSEA results suggested that low SPARCL1 expression in BC was related to the cell cycle, DNA replication, oxidative phosphorylation, and homologous recombination. Lower expression levels of SPARCL1 were detected in BC tissues compared to adjacent tissues. The in vitro experiments showed that SPARCL1 knockdown significantly increased the proliferation and migration of BC cells, whereas the proliferation and migration were suppressed after elevating the expression of SPARCL1. We identified SPARCL1 as a tumor suppressor in BC, which shows potential as a target for BC and liver metastasis therapy and diagnosis.

Artificial intelligence-powered software detected more than half of the liver metastases overlooked by radiologists on contrast-enhanced CT

PurposeTo evaluate the sensitivity of artificial intelligence (AI)-powered software in detecting liver metastases, especially those overlooked by radiologists. MethodsRecords of 746 patients diagnosed with liver metastases (November 2010–September 2017) were reviewed. Images from when radiologists first diagnosed liver metastases were reviewed, and prior contrast-enhanced CT (CECT) images were checked for availability. Two abdominal radiologists classified the lesions into overlooked lesions (all metastases missed by radiologists on prior CECT) and detected lesions (all metastases if any of them were correctly identified and invisible on prior CECT or those with no prior CECT). Finally, images from 137 patients were identified, 68 of which were classified as “overlooked cases.” The same radiologists created the ground truth for these lesions and compared them with the software’s output at 2-month intervals. The primary endpoint was the sensitivity in detecting all liver lesion types, liver metastases, and liver metastases overlooked by radiologists. ResultsThe software successfully processed images from 135 patients. The per-lesion sensitivity for all liver lesion types, liver metastases, and liver metastases overlooked by radiologists was 70.1%, 70.8%, and 55.0%, respectively. The software detected liver metastases in 92.7% and 53.7% of patients in detected and overlooked cases, respectively. The average number of false positives was 0.48 per patient. ConclusionThe AI-powered software detected more than half of liver metastases overlooked by radiologists while maintaining a relatively low number of false positives. Our results suggest the potential of AI-powered software in reducing the frequency of overlooked liver metastases when used in conjunction with the radiologists’ clinical interpretation.

Tumour-derived exosomes in liver metastasis: A Pandora's box.

The liver is a common secondary metastasis site of many malignant tumours, such as the colorectum, pancreas, stomach, breast, prostate, and lung cancer. The clinical management of liver metastases is challenging because of their strong heterogeneity, rapid progression, and poor prognosis. Now, exosomes, small membrane vesicles that are 40-160 nm in size, are released by tumour cells, namely, tumour-derived exosomes (TDEs), and are being increasingly studied because they can retain the original characteristics of tumour cells. Cell-cell communication via TDEs is pivotal for liver pre-metastatic niche (PMN) formation and liver metastasis; thus, TDEs can provide a theoretical basis to intensively study the potential mechanisms of liver metastasis and new insights into the diagnosis and treatment of liver metastasis. Here, we systematically review current research progress about the roles and possible regulatory mechanisms of TDE cargos in liver metastasis, focusing on the functions of TDEs in liver PMN formation. In addition, we discuss the clinical utility of TDEs in liver metastasis, including TDEs as potential biomarkers, and therapeutic approaches for future research reference in this field.

Clinical and radiological response to locoregional and systemic treatments in well-differentiated gastroenteropancreatic neuroendocrine tumors with liver metastases treated at a reference center in Mexico.

644 Background: liver metastases (LM) from well-differentiated gastroenteropancreatic neuroendocrine tumors (wd-GEP-NET) can develop in 28-77% of patients (pts) in their lifetime. Multiple treatments can provide radiological and symptomatic response. Our aim was to evaluate responses to locoregional (LRT) and systemic (SYST) treatments in wd-GEP-NET with LM. Methods: we included consecutive records of pts with confirmed histological diagnosis of wd-GEP-NET and radiological LM, treated at our institution between 2008-2019. Relevant variables were retrospectively extracted from electronic records. Radiological response was assessed with RECIST 1.1 by radiological independent review. Results: 55 pts, 45.5% male. Median age at LM diagnosis 49 years (IQR 41-63). Primary tumor sites: 49% pancreatic, 27.3% small intestine, 11% unknown, 12.7% others. WHO 2019 grade 1, 2 and 3 in 52.7, 41.8 and 1.8%, respectively. Twentynine tumors (52.7%) were functional, with carcinoid syndrome in n20. At LM diagnosis, 91% of pts had symptomatic disease: hormonal n8, local n4, systemic n4, hormonal + local n4, local + systemic n22, hormonal + systemic n5, hormonal + local + systemic n5. LM tumoral burden was &lt;10% in 22%, 11-50% in 43.6, &gt; 50% in 30.9% of pts. 49.1% of pts had extra hepatic metastatic disease. LRT to LM was administered to 32 pts: TAE/TACE n26, ablation n8. SYST to 22 pts: somatostatin analog n15, Lutetium-177 n4, chemotherapy n2, everolimus n1. 1 pt did not receive treatment. Response to treatments is shown. In the LRT group, -- pts developed complications: n16 postembolization syndrome, n2 infections, n3 liver failure, n7 others. There was 1-procedure-related death. Conclusions: Patients treated with LRT at our institution achieved similar efficacy and safety results compared to those reported by previous studies.[Table: see text]

China guideline for diagnosis and comprehensive treatment of colorectal liver metastases (version 2023)

The liver is the main target organ for hematogenous metastases of colorectal cancer, and colorectal liver metastasis is one of the most difficult and challenging situations in the treatment of colorectal cancer. In order to improve the diagnosis and comprehensive treatment of colorectal liver metastasis in China, the guidelines have been edited and revised for several times since 2008, including the overall evaluation, personalized treatment goals and comprehensive treatments, to prevent the occurrence of liver metastases, increase the local damage rate of liver metastases, prolong long-term survival, and improve quality of life. The revised guideline version 2023 includes the diagnosis and follow-up, prevention, multidisciplinary team (MDT), surgery and local ablative treatment, neoadjuvant and adjuvant therapy, and comprehensive treatment, with state-of-the-art experience and findings, detailed content, and strong operability.

Molecular mechanisms investigation for liver metastasis of colorectal cancer by combined bioinformatic gene expression profile analysis

Background: Colorectal cancer (CRC) is one of the most common cancers worldwide. As the molecular mechanism for liver metastasis of CRC has not yet been completely discovered, identification of hub genes and pathways of this disease is of importance for revealing potential molecular mechanism of colorectal cancer progression. This study aimed to identify potential biomarkers and survival analysis of hub genes for CRC treatment. Methods: The differentially expressed genes (DEGs) between colorectal cancer liver metastasis and primary tumor were screened using microarray data from two datasets GSE179979, GSE144259 obtained from the Gene Expression Omnibus (GEO) database. Gene ontology (GO) and KEGG pathway enrichment analyses were performed for DEGs using DAVID database, the protein-protein interaction (PPI) network was constructed using the Cytoscape software, and module analysis was performed using MCODE. Then, overall survival (OS), progression free interval (PFI) and disease specific survival (DSS) analysis of hub genes was performed by using TCGA database. The correlations between hub genes and clinical values were validated through CRN and immunohistochemistry (IHC) stain. Results: A total of 64 DEGs were obtained, KEGG pathway analysis showed that the significant pathways included PPAR signaling pathway, Complement and coagulation cascades. Four hub genes (ITIH2, ALB, CPB2, HGFAC) and two biomarkers (CPB2, HGFAC) with significantly prognostic values were verified by Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) cohort. Conclusions: CPB2 and HGFAC may serve as new biomarkers in diagnosing liver metastasis of CRC or potential drug target.

The role of [99mTc]Tc-HFAPi SPECT/CT in patients with malignancies of digestive system: first clinical experience

BackgroundRecently, PET/CT imaging with radiolabelled FAP inhibitors (FAPIs) has been widely evaluated in diverse diseases. However, rare report has been published using SPECT/CT, a more available imaging method, with [99mTc]Tc-labelled FAPI. In this study, we evaluated the potential effect of [99mTc]Tc-HFAPi in clinical analysis for digestive system tumours.MethodsThis is a single-centre prospective diagnostic efficiency study (Ethic approved No.: XJTU1AF2021LSK-021 of the First Affiliated Hospital of Xi’an Jiaotong University and ChiCTR2100048093 of the Chinese Clinical Trial Register). Forty patients with suspected or confirmed digestive system tumours underwent [99mTc]Tc-HFAPi SPECT/CT between January and June 2021. For dynamic biodistribution and dosimetry estimation, whole-body planar scintigraphy was performed at 10, 30, 90, 150, and 240 min post-injection in four representative patients. Optimal acquisition time was considered in all the patients at 60–90 min post-injection, then quantified or semi-quantified using SUVmax and T/B ratio was done. The diagnostic performance of [99mTc]Tc-HFAPi was calculated and compared with those of contrast-enhanced CT (ceCT) using McNemar test, and the changes of tumour stage and oncologic management were recorded.ResultsPhysiological distribution of [99mTc]Tc-HFAPi was observed in the liver, pancreas, gallbladder, and to a lesser extent in the kidneys, spleen and thyroid. Totally, 40 patients with 115 lesions were analysed. The diagnostic sensitivity of [99mTc]Tc-HFAPi for non-operative primary lesions was similar to that of ceCT (94.29% [33/35] vs 100% [35/35], respectively; P = 0.5); in local relapse detection, [99mTc]Tc-HFAPi was successfully detected in 100% (n = 3) of patients. In the diagnosis of suspected metastatic lesions, [99mTc]Tc-HFAPi exhibited higher sensitivity (89.66% [26/29] vs 68.97% [20/29], respectively, P = 0.03) and specificity (97.9% [47/48] vs 85.4% [41/48], respectively, P = 0.03) than ceCT, especially with 100% (24/24) specificity in the diagnosis of liver metastases, resulting in 20.0% (8/40) changes in TNM stage and 15.0% (6/40) changes in oncologic management.Conclusion[99mTc]Tc-HFAPi demonstrates a greater diagnostic efficiency than ceCT in the detection of distant metastasis, especially in identifying liver metastases.

Will Patients With Liver Metastasis From Aggressives Cancers Benefit From Surgical Resection?

We aimed to evaluate the outcomes of resections for liver metastases (LMs) originating from pancreatic ductal adenocarcinoma (PDAC), non-small cell lung cancer (NSCLC), and esophagus/gastric cancers (EGCs), which we label as major killers (MKs; overall survival (OS) under 10%). We hypothesized that LM resection must provide the patient with almost a year of OS postoperatively that is considered beneficial. From January 2005 to December 2020, 23 patients underwent resection for isolated LM from MKs. These patients underwent surgery after a multidisciplinary discussion about their performance status, disease evolution during prolonged medical treatment, and the existence or absence of extrahepatic metastases. LM originated from an PDAC, EGC, or NSCLC in 10 patients (43%), nine patients (39%), and four patients (18%), respectively. The median delay between primary cancer and LM diagnoses was 12 months, and the median delay between LM diagnosis and liver resection was 10 months. Most patients, who had objectively responded to medical treatment (57%), had a solitary (61%) and unilobar (70%) LM. Severe morbidity and 90-day mortality rates were 13% and 4.3%, respectively. Margin-free resection was achieved in 16 patients (70%). After liver resection, the median OS was 24 months without a statistical difference when considering the primary tumor site; 1, 3-, and 5-year OS were 70%, 23%, and 23%, respectively. Selection based on criteria such as good clinical condition, response to treatment, and long observation period helped identify patients with LM of MKs who seemed to benefit from resection.

Development and validation of a nomogram to predict liver metastasis for pancreatic ductal adenocarcinoma after radical resection.

This study aimed to develop and externally validate a nomogram for predicting liver metastasis after radical resection in patients with pancreatic ductal adenocarcinoma (PDAC). A total of 247 PDAC patients who underwent radical resection were retrospectively reviewed from January 2015 to March 2022 at Ningbo Medical Centre Lihuili Hospital Eastern Section, and used as a training cohort to develop the nomogram. 83 PDAC patients from the Ningbo Medical Centre Lihuili Hospital Xingning Section were enrolled as the validation cohort. The postoperative liver metastasis was recorded during the follow-up, and the liver metastasis-free survival was defined as the time from operation to the date of liver metastasis diagnosis or death. The nomogram was established based on independent prognostic factors selected by LASSO and multivariate Cox regression model. The performance was assessed using the concordance index (C-index) and calibration curves. The receiver operating characteristic (ROC) curve and decision curve analysis (DCA) were used to determine the clinical utility of the nomogram model. From the training cohort of 247 patients, a total of 132 patients developed liver metastasis during the follow-up, the 1-, 2- and 3- year liver metastasis-free survival were 52.4%, 43.5% and 40% respectively. The LASSO and multivariate Cox regression analysis indicated that postoperative CA125 (hazard ratio [HR] = 1.007, p <0.001), tumor differentiation (HR = 1.640, p = 0.010), tumor size (HR = 1.520, p = 0.029), lymph node ratio (HR = 1.897, p = 0.002) and portal/superior mesenteric/splenic vein invasion degree (PV/SMV/SV) (HR = 2.829, p <0.001) were the independent factors of liver metastasis. A nomogram with independent factors was developed and the C-index was 0.760 (95% confidence interval [CI], 0.720-0.799) and 0.739 (95% CI, 0.669-0.810) in the training and validation cohorts, respectively. The areas under curve (AUC) of the nomogram at 1-, 2- and 3-year were 0.815, 0.803 and 0.773 in the training cohort, and 0.765, 0.879 and 0.908 in the validation cohort, respectively, higher than those in TNM stage. Decision curve analysis (DCA) analysis revealed that the nomogram model provided superior net benefit in clinical utility. Liver metastasis-free survival curves showed a significant discriminatory ability for liver metastasis risk based on the nomogram (p <0.001). The nomogram showed high accuracy in predicting liver metastasis for PDAC after radical resection, and may serve as a clinical support tool to guide personalized and prescient intervention.

Single Photon Emission Computed Tomography (SPECT) Functional Liver Imaging to Facilitate Reirradiation for Liver Malignancies: A Phase 1 Trial

<h3>Purpose/Objective(s)</h3> Functional imaging, such as Tc-99m- sulfur colloid single photon emission computed tomography (SPECT), may allow preferential sparing of functional liver volume and facilitate safe reirradiation. The primary objective of this study is to evaluate the safety of hypofractionated reirradiation for patients with hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (IHC) or liver metastases (LM) who received prior radiation with either external beam radiotherapy (EBRT) or yttrium-90 radioembolization (Y90 RE) when using SPECT functional liver imaging for planning. <h3>Materials/Methods</h3> This is a Phase I trial with a 3+3 design used to test three levels of dose constraints for safety. Eligible patients had a diagnosis of HCC, IHC or LM and received EBRT >/=12 months prior or Y90 RE >/=6 months prior. After giving informed consent, patients underwent simulation and subsequent SPECT scan in the treatment position. Functional liver was estimated based on 40% maximum intensity as threshold. The prescription dose was 45Gy-67.5Gy in 15 fractions. Composite constraints were bowel/duodenum/stomach Dmax <45Gy, esophagus Dmax <50Gy, common bile duct Dmax <60Gy, and V45Gy <10% for the heart. The mean functional liver dose constraint was <20Gy or 18Gy for patients treated with EBRT and Y90 RE, respectively. The volumetric dose constraint for functional liver volume receiving <22Gy depended on the dose level of trial enrollment: level 0 was ≥400cc, level -1 was 500cc and level +1 was 300cc. Dose limiting toxicities (DLTs), including grade 3 hypoalbuminemia, increase in INR, increase in bilirubin, ascites or hepatic failure as well as any grade 4 toxicity related to reirradiation, were assessed within 2 months after re-radiation. Any liver decompensation qualifying as a DLT was attributed to radiation therapy. The maximal dose constraint (MDC) is defined as the highest constraint level at which no more than one patient has experienced DLT in six patients treated at that dose constraint. <h3>Results</h3> A total of thirteen patients were enrolled between May 2018 and April 2021. The median [IQR] reirradiation GTV volume was 57cc [32-287cc]. The median [IQR] liver-minus-GTV and functional liver volumes were 1402cc [1141-1481cc] and 869 [784-1077], respectively. All plans spared >/=500ccs of functional liver from receiving ≥22Gy (median [IQR] 726 [637-783]). The median [IQR] mean function liver volume dose was 14.9Gy [10.4-18.6Gy]. The first 3 patients in dose level 0 and the next 3 patients treated in dose level +1 experienced no DLTs. Of the next seven patients treated using dose level +1 constraints, one developed a DLT possibly attributable to radiation. <h3>Conclusion</h3> SPECT functional imaging facilitates safe reirradiation for primary and metastatic liver tumors. Due to the ability to spare >/=500ccs of functional liver from >22Gy for all patients with only 1 of 13 patients experiencing DLT, we conclude this to be a reasonable constraint for reirradiation.