Sarcopenia worsening after transarterial radioembolization with Holmium-166 predicts progressive disease in patients with advanced hepatocellular carcinoma.

Sarcopenia worsening after transarterial radioembolization with Holmium-166 predicts progressive disease in patients with advanced hepatocellular carcinoma. | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Sarcopenia worsening after transarterial radioembolization with Holmium-166 predicts progressive disease in patients with advanced hepatocellular carcinoma. Claudio Trobiani, Nicolò Ubaldi, Leonardo Teodoli, Federico Cappelli, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3429080/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose: To investigate the association between changes in sarcopenia before and after one-three months of Transarterial Radioembolization (TARE) treatment with Holmium-166 (166Ho) for hepatocellular carcinoma (HCC) and its impact on the rate of local response. Methods: A retrospective single center analysis was conducted on 20 HCC patients who underwent 166Ho-TARE. Patients were categorized into two groups based on the change in psoas muscle index (PMI) measured at the time of TARE and one-three months after: No-Sarcopenia group (deltaPMI stable or increased; n = 9) and Sarcopenia group (deltaPMI decreased; n = 7). DeltaPMI was associated to the local response rate, according to mRECIST criteria. Results: DeltaPMI was evaluated according to mRECIST criteria: non-responder group (standard and progression disease) and responder group (complete response or partial response). Three months after TARE, a significant difference in sarcopenia status was observed (p = 0.041), with a median deltaPMI of -0.57 in the non-responder and 0.12 in the responder group. DeltaPMI measured three months after TARE can be considered as a predictive biomarker of the local response rate (p=0.028). Conclusion: Sarcopenia deterioration at three months from TARE with Holmium-166 is a reliable predictor of worse loco-regional response rate, evaluated radiologically, in HCC patients. Health sciences/Biomarkers Health sciences/Oncology TARE Sarcopenia HCC Interventional Oncology Liver Holmium-166 Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 INTRODUCTION Primary liver cancer was diagnosed in roughly 800.000 patients worldwide in 2022, accounting for more than 700.000 deaths yearly [ 1 ]. Transarterial radioembolization (TARE) is a minimally invasive treatment which combines low volume arterial embolization and internal radiation therapy. TARE is generally considered safe and efficacious for unresectable hepatocellular carcinoma (HCC), demonstrating improvement of overall survival compared to conventional treatment [ 2 ]. From its invention as a palliative treatment in the 1960’s [ 3 ], late in 2022 TARE has entered at the left of the Barcelona Clinic Liver Cancer algorithm in the early stage section (i.e., BCLC 0-A), in case of impossibility or failure of the mainstay treatments available in HCC disease [ 4 ]. Recently, in a phase II randomized trial (TRACE) comparing TARE and transarterial chemoembolization (TACE) in patients with early or intermediate stage HCC, TARE demonstrated a better tumor control and overall survival [ 5 ]. With respect to TACE, TARE generates lower toxicity radiating to the healthy parenchyma in addition to reduced static embolization effects, intuitively causing less damage on the hepatocytes, therefore it was better tolerated and may be preferable in patients with portal vein thrombosis [ 6 , 7 ]. Appropriateness of TARE is evaluated through a multidisciplinary oncologic team; generally considering applicants with > 3 months of life expectancy, bilirubin 3 g/dL and an eastern cooperative oncology group (ECOG) status ≤ 2 [ 8 ]. Different radionuclides are used for TARE, Yttrium-90 (90Y) being the most utilized even though Holmium-166 (166Ho) microspheres are considered as an alternative. Poly-L-lactic acid makes the basis of 166Ho, and compared to Yttrium-90, it has the advantage of possessing both high energy beta emission for the treatment procedure and lower gamma emission for the scout, the latter evaluated using SPECT imaging. Furthermore, thanks to its paramagnetic properties, the distribution and quantification of tumor dose load can also be assessed conveniently using MRI [ 9 , 10 ]. Commonly, 166Ho is loaded in either resin or glass microspheres, the prior being more readily available and carries lower density [ 8 ]. Holmium possesses a relatively medium-short half-life of 26.8h resulting in a high dose rate in a short period and thus allowing the evaluation of the treatment response, through CT, FDG-PET or MRI, at shorter time interval compared to 90Y, usually < 6 months in our clinical practice. Various prognostic staging systems have been developed for HCC, nevertheless the patients’ performance status remains poorly touched [ 11 ]. Sarcopenia, defined as the “progressive loss of muscle mass and strength with a risk of adverse outcomes such as disability, poor quality of life and death” [ 12 ], occurs relatively early in HCC disease and can independently negatively predict HCC related mortality in patients undergoing locoregional treatment [ 11 , 12 , 13 ]. In fact, sarcopenia has been associated to lack of treatment response for HCC [ 14 ], and lately it has been confirmed as a predictor of progressive disease in HCC treated also with TARE-90Y [ 13 ]. Because sarcopenia could be used to assess overall response of locoregional treatment of HCC [ 15 , 16 , 13 ], specific population of patients with worsening sarcopenia should be carefully identified as these could benefit an early locoregional retreatment and a nutritional supportive strategy to restore muscle mass and strength. The aim of this study is to assess whether there is a potential relationship between changes in sarcopenia before and after one-three months of TARE-166Ho treatment and the rate of local response it induces, so to determine if the deterioration of sarcopenia worsening can serve as an early identificatory of a subset of patients who are at a high risk of disease progression. MATERIAL AND METHODS Patients A retrospective investigation was conducted on 20 patients with HCC who underwent TARE-166Ho, between the period 2021–2023. The analysis involved assessing the radiological response, according to mRECIST criteria, one and three months subsequent to the procedure. The local response rate was evaluated for all patients one month and three months after TARE procedure. The entire population was divided in two groups according to the delta value of the psoas muscle index (PMI) measured at the time of TARE, one-three months after TARE. The two groups were defined as follows: patients in which the delta PMI was stable or increased (No-Sarcopenia group; n = 9) vs. patients in which the delta-PMI decreased (Sarcopenia group; n = 7). The study was carried out in compliance with the guidelines of the Declaration of Helsinki, and this study was accepted by the local ethical committee. TARE All procedures were carried out by experienced interventional radiologists with more than five years of experience. For the treatment, 80–170 MBq 166mHo-loaded scout microspheres were administered slowly through a 2.7-F micro-catheter (Progreat; Terumo Europe NV, Leuven, Belgium) placed in the pathological feeder artery. The distribution of the drug was assessed using SPECT imaging. Post-therapy SPECT/CT scans (Symbia IntevoTM system; Siemens, Erlangen, Germany) were performed between 1 and 20 hours after SIRT to evaluate the distribution of the microspheres thanks to 2D and 3D dosimetry maps. Firstly, the accuracy and intensity of the 166Ho-microspheres activity distribution were evaluated by analyzing the 2D activity intensity peak (Pixel Value) of the signal along a line crossing the treated area. A higher peak indicated a more intense signal within the targeted area. Later, the 3D effective dose in Gy distributed to the lesion and liver parenchyma per unit cumulated activity (GBq), was calculated according to the activity distribution obtained from SPECT/CT imaging, utilizing a MIM 6.1.7 workstation (MIM Software Inc., Cleveland, Ohio). For each patient, the mean absorbed dose () in Gy for the normal liver and tumor were compared with the expected values ( to tumor > 100 Gy, to normal liver < 40 Gy) to assess the treatment efficacy. Sarcopenia measurement The assessment of sarcopenia status was determined by measuring the PMI. The PMI was calculated using the following formula: PMI [mm/m^2]: [(minor diameter of left psoas + major diameter of left psoas + minor diameter of right psoas + major diameter of right psoas)/4]/height in m^2 [ 17 ]. All the psoas measurements were performed at the level of L3-L4 (Figs. 1 and 2 ). Statistical analysis The Mann–Whitney U test was used for evaluating the delta-PMI according to treatment response at 1 and 3 months after TARE. The PMI at the time of TARE was compared with the PMI measurements at one and three months after TARE. The delta-PMI measurements between the first PMI measurement and the controls at one and three months were evaluated. Variables with a p < 0.05 were considered statistically significant. The accuracy of the different sarcopenia measurements performed over time was assessed through c-statistics analysis, with the intent to evaluate their ability to predict the progressive disease after TARE. Areas under the curve (AUCs) and 95% CI were reported. Fisher’s exact test was used for comparisons of categorical variables, respectively. RESULTS The deltaPMI measured before (base value) and 1 month after TARE was evaluated after grouping response labels as follows: standard and progression disease were joined as the non-responder group and complete response or partial response were joined as the responder group. No statistically significant difference (p = 0.229) was observed in terms of sarcopenia status, with a median deltaPMI of 0 vs. -0.44 in the responder and non-responder group, respectively (Fig. 3 ). The deltaPMI measured before (base value) and 3 months after TARE was also evaluated between the non-responder and responder group (Fig. 4 ). A statistically significant difference (p = 0.041) was observed in terms of sarcopenia status, with a median deltaPMI of 0.12 vs. -0.57 in the responder and non-responder group, respectively. A further Mann-Whitman test was conducted to investigate whether deltaPMI could be predictive of a response constant over time. For this purpose, a variable named bestresp was introduced and defined as follows: if the response after one month is confirmed after three months and 0 otherwise. No statistically significant relevance (p = 0.247) was observed for data collected one month after TARE, probably due to the fact that is premature to evaluate the radiological response to TARE treatment only one month after the procedure (Fig. 5 ). The same analysis conducted 3 months after TARE showed that deltaPMI can be considered as a predictive biomarker of local response rate (p = 0.028). In particular, we found out that a strong negative variation of PMI is associated with a poor response to treatment with a median deltaPMI of -0.57 in the non-responder and 0.12 in the responder group, respectively (Fig. 6 ). It was interesting to note that the diagnostic ability for stable or progressive disease of the sarcopenia measurement increased with time after the TARE procedure. The ROC analysis was also used to investigate the optimal cut-off of deltaPMI that is statistically relevant in the prediction of a bestresp (i.e. a response to treatment constant over time). At three months, the deltaPMI value had an AUC = 0.875 (p = 0.0001, CIs 0.617 to 0.984). In particular, a PMI variation greater than − 0.293 resulted to be associated with a bestresp. This seems to confirm that a small deltaPMI variation is predictive of a good treatment. In fact, all 9 patients (100%) who showed a PMI variation greater than the cut-off had a good response to treatment (Fisher’s exact test, p = 0.019). DISCUSSION Sarcopenia deterioration at three months after TARE treatment with Holmium-166 is a reliable predictor of worse loco-regional response rate, in HCC patients. Sarcopenia has functioned as a predictive element across various clinical scenarios. It has been employed as a predictive factor among patients with HCC [ 18 ], including patients undergoing Sorafenib [ 19 , 20 ], intra-arterial chemoembolization [ 17 ], and pre- or post-transplant [ 21 ]. Recently, sarcopenia worsening after TARE treatment with Yttrium-90 has been associated with progressive disease in the early stages [ 13 ]. The most recent Holmium-166 radionuclide has been established as a valid alternative to Yttrium-90 in TARE, also in consideration of the advantages it manifests. The analysis conducted at the three-month mark post-TARE-166Ho revealed that the difference in PMI, before and after the procedure, holds potential as a predictive biomarker of the local response rate (p = 0.028). Notably, our findings indicated a negative shift in PMI correlated with an unfavorable treatment response, as evidenced by a median deltaPMI of -0.57 in the non-responder group, compared to a median value of 0.12 in the responder cohort (p = 0.041). It was observed that the diagnostic efficacy of sarcopenia measurement in discerning stable or progressive disease displayed an augmenting trend over time, from one to three months, subsequent to the TARE procedure. This highlights the strength of sarcopenia measurement in predicting effectively the intermediate local outcome, after TARE-166Ho. As such, sarcopenia worsening is correlated with a worse mRECIST score in the intermediate stage. Furthermore, this approach was consistent among both males and females, regardless of the initial morphological differences that existed between the two genders. Conversely, no statistically significant PMI differences at one month after procedure was observed in both groups, likely attributable to the premature nature of assessing the radiological response to TARE treatment within just one month after the procedure. Moreover, the pre-procedural assessment of sarcopenia status exhibited no statistically significant distinctions between the cohort of patients experiencing progressive disease and those achieving complete response, partial response, or stable disease. This implies that the initial evaluation of sarcopenia cannot serve as a reliable predictor for unfavorable oncological outcomes following transarterial radioembolization. The assessment of TARE treatment response has been evaluated through CT and MRI, or FDG-PET scans. However, these techniques necessitate a minimum of three months to furnish accurate insights into TARE outcomes [ 22 ]. In addition to what previously published illustrating the association between sarcopenia worsening and HCC progression at 1 and 3 months after TARE-90Y, this study confirms the same outcomes utilizing Holmium-166. The divergence in sarcopenia status, evidenced three months post-procedure through routinely conducted multiphasic CT scans, presents a convenient non-invasive predictive biomarker for treatment efficacy, confirming the association of skeletal muscle depletion in predicting worse loco-regional response rate. Patients could benefit from early skeletal muscle depletion adjustment by simple non-invasive methods that would aid in the clinical management by reducing the probability of disease progression, according to these data. Swift identification of declining sarcopenia could prompt the implementation of aggressive support protocols. Multimodal approaches encompassing nutritional support, physical therapy, and medications such as ibuprofen (Menac trial) and selective androgen receptor modulators and ghrelin receptor activation with agonists, are recognized as foundational in managing sarcopenia. Interestingly, the initial sarcopenic status could guide the selection of a subset of HCC patients undergoing TARE as a preparatory measure for liver transplant. As such, sarcopenia status could aid in identifying individuals with predictable positive outcomes following transplantation and that would mostly benefit from it. On the other end of the spectrum, the prompt identification of patients at risk of non-responsiveness could offer utility by guiding the early implementation of systemic therapies. Furthermore, the potential for sarcopenia status to forecast disease progression could aid in identifying candidates for early TARE retreatment. In fact, retreatment discussions cases where patients tolerated the initial procedure without substantial improvement, often not accounting for the necessary CT/MRI assessment time-frame, although there is no consensus regarding the optimal timing for retreatment. The study has several limitations that need discussion. Foremost, the retrospective nature of the study design precludes the establishment of a randomized framework, which may influence the generalizability of the findings. Secondly, the sample size under analysis was relatively modest, thus these results must be validated by further studies with larger population size. The future trajectory of research would ideally encompass both larger retrospective studies, but more notably, prospective and randomized studies to confirm and further validate these results. CONCLUSIONS TARE treatment is now a firmly established therapeutic option for patients dealing with locally advanced hepatocellular carcinoma, more recently Holmium-166 has opened new horizons in this population thanks to various advantages it fosters. Nonetheless, assessing the response to TARE treatment during the initial stages of follow-up is often challenging. Sarcopenia deterioration is a reliable predictor of worse local response rate at three months after TARE-166Ho, and could serve as a valuable indicator for identifying patients who are at a heightened risk of disease progression. In fact, PMI decreased significantly more in the group of poor responders. Should our findings be substantiated, they could play a pivotal role in the early identification of patients who do not respond to the treatment and whom may benefit from prompt integrative restorative treatment. Declarations Acknowledgements: Not applicable. Funding: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Competing Interests: The authors have no relevant financial or non-financial interests to disclose. Author Contributions: All authors made substantial contributions in conception and design of the article, acquisition, analysis and interpretation of data, drafting of the article and final approval of the version to be published. CT, GV, LT were responsible for conceptualization. NU, SU were responsible for data curation. GV were responsible for project administration. CT, NU were responsible for writing-original draft. SU was responsible for formal analysis and methodology. NU, CT were responsible for writing—review & editing. GV, FC were responsible for supervision. Data Availability: The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request. Consent to participate: Informed consent was obtained from all individual participants included in the study. Consent for publication: The authors affirm that human research participants provided informed consent for publication of the images in Figure(s) 1-6. Ethics approval: This is an observational retrospective study and the Ethical Committee Lazio Area 5 evaluated this research study under the registral sperimental number N. 1561/21. References Oh JH, Jun DW. The latest global burden of liver cancer: A past and present threat. Clin Mol Hepatol . 2023;29(2):355-357. doi:10.3350/cmh.2023.0070 D’Avola D, Lñarrairaegui M, Bilbao JI, et al. A retrospective comparative analysis of the effect of Y90-radioembolization on the survival of patients with unresectable hepatocellular carcinoma. Hepatogastroenterology . 2009;56(96):1683-1688. Ariel IM, Pack GT. Treatment of inoperable cancer of the liver by intra-arterial radioactive isotopes and chemotherapy. 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Significance of psoas muscle thickness as an indicator of muscle atrophy in patients with hepatocellular carcinoma treated with sorafenib. Mol Clin Oncol . 2017;7(3):449-453. doi:10.3892/mco.2017.1321 Ahmadzadehfar H, Duan H, Haug AR, Walrand S, Hoffmann M. The role of SPECT/CT in radioembolization of liver tumours. Eur J Nucl Med Mol Imaging . 2014;41 Suppl 1:S115-124. doi:10.1007/s00259-013-2675-5 Adcock CS, Florez E, Zand KA, Patel A, Howard CM, Fatemi A. Assessment of Treatment Response Following Yttrium-90 Transarterial Radioembolization of Liver Malignancies. Cureus . 2018;10(6):e2895. doi:10.7759/cureus.2895 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Italy","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Sara","middleName":"","lastName":"Ungania","suffix":""},{"id":243154725,"identity":"7a32cc70-490f-4d52-8f1b-02bbfed871c2","order_by":5,"name":"Giulio Vallati","email":"","orcid":"","institution":"Interventional Radiology Unit of \"IRCCS Istituto Nazionale Tumori Regina Elena\", 00138 Rome, Italy","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Giulio","middleName":"","lastName":"Vallati","suffix":""}],"badges":[],"createdAt":"2023-10-10 21:44:14","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3429080/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3429080/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":45478639,"identity":"72b410d6-6bde-40fe-bf90-fef7850401ea","added_by":"auto","created_at":"2023-10-30 19:55:08","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":397264,"visible":true,"origin":"","legend":"\u003cp\u003eSarcopenia status measured before TARE in the Sarcopenia group (A) and No-Sarcopenia group (B).\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-3429080/v1/f483f18edac62b5285beeb2c.png"},{"id":45478641,"identity":"354bda10-e63e-4536-bc9a-7c171ce688e3","added_by":"auto","created_at":"2023-10-30 19:55:08","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":425956,"visible":true,"origin":"","legend":"\u003cp\u003eSarcopenia status measured after TARE in the Sarcopenia group (A) and No-Sarcopenia group (B).\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-3429080/v1/9a9ee1fb0919694a9d26c7f5.png"},{"id":45478638,"identity":"ec47d3f3-538c-4c05-8d60-9687315ee50a","added_by":"auto","created_at":"2023-10-30 19:55:08","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":41224,"visible":true,"origin":"","legend":"\u003cp\u003eDeltaPMI after 1 month evaluated against response to treatment.\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-3429080/v1/11479829d68f54e50031cbba.png"},{"id":45478643,"identity":"bead6e2e-a1bf-4d2e-b08b-8cdd4918b862","added_by":"auto","created_at":"2023-10-30 19:55:08","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":316742,"visible":true,"origin":"","legend":"\u003cp\u003eDeltaPMI after 3 months evaluated against response to treatment.\u003c/p\u003e","description":"","filename":"floatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-3429080/v1/6ca06e7b6bdce2e9f39fabb6.png"},{"id":45478640,"identity":"ab9a7c97-5faf-491c-9093-9b1d3606b654","added_by":"auto","created_at":"2023-10-30 19:55:08","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":296507,"visible":true,"origin":"","legend":"\u003cp\u003eDeltaPMI after 1 month evaluated against the \u003cem\u003ebestresp\u003c/em\u003e variable.\u003c/p\u003e","description":"","filename":"floatimage5.png","url":"https://assets-eu.researchsquare.com/files/rs-3429080/v1/3539e9ad0da9f517bd0cadc1.png"},{"id":45478642,"identity":"484be9d2-b07a-45cd-82ed-dab31ad7673a","added_by":"auto","created_at":"2023-10-30 19:55:08","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":311391,"visible":true,"origin":"","legend":"\u003cp\u003eDeltaPMI after 3 months evaluated against the \u003cem\u003ebestrep\u003c/em\u003e variable.\u003c/p\u003e","description":"","filename":"floatimage6.png","url":"https://assets-eu.researchsquare.com/files/rs-3429080/v1/6ad758ab3a6e7e853d9629b0.png"},{"id":49678037,"identity":"1fbd7ba4-9841-4ebc-acf9-497d38131011","added_by":"auto","created_at":"2024-01-16 10:37:34","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2065716,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3429080/v1/600536b7-5399-40c4-a294-a6f971b55239.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eSarcopenia worsening after transarterial radioembolization with Holmium-166 predicts progressive disease in patients with advanced hepatocellular carcinoma.\u003c/p\u003e","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003ePrimary liver cancer was diagnosed in roughly 800.000 patients worldwide in 2022, accounting for more than 700.000 deaths yearly [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Transarterial radioembolization (TARE) is a minimally invasive treatment which combines low volume arterial embolization and internal radiation therapy. TARE is generally considered safe and efficacious for unresectable hepatocellular carcinoma (HCC), demonstrating improvement of overall survival compared to conventional treatment [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. From its invention as a palliative treatment in the 1960\u0026rsquo;s [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e], late in 2022 TARE has entered at the left of the Barcelona Clinic Liver Cancer algorithm in the early stage section (i.e., BCLC 0-A), in case of impossibility or failure of the mainstay treatments available in HCC disease [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Recently, in a phase II randomized trial (TRACE) comparing TARE and transarterial chemoembolization (TACE) in patients with early or intermediate stage HCC, TARE demonstrated a better tumor control and overall survival [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. With respect to TACE, TARE generates lower toxicity radiating to the healthy parenchyma in addition to reduced static embolization effects, intuitively causing less damage on the hepatocytes, therefore it was better tolerated and may be preferable in patients with portal vein thrombosis [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Appropriateness of TARE is evaluated through a multidisciplinary oncologic team; generally considering applicants with \u0026gt;\u0026thinsp;3 months of life expectancy, bilirubin\u0026thinsp;\u0026lt;\u0026thinsp;2 mg/dL, albumin\u0026thinsp;\u0026gt;\u0026thinsp;3 g/dL and an eastern cooperative oncology group (ECOG) status\u0026thinsp;\u0026le;\u0026thinsp;2 [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eDifferent radionuclides are used for TARE, Yttrium-90 (90Y) being the most utilized even though Holmium-166 (166Ho) microspheres are considered as an alternative. Poly-L-lactic acid makes the basis of 166Ho, and compared to Yttrium-90, it has the advantage of possessing both high energy beta emission for the treatment procedure and lower gamma emission for the scout, the latter evaluated using SPECT imaging. Furthermore, thanks to its paramagnetic properties, the distribution and quantification of tumor dose load can also be assessed conveniently using MRI [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Commonly, 166Ho is loaded in either resin or glass microspheres, the prior being more readily available and carries lower density [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Holmium possesses a relatively medium-short half-life of 26.8h resulting in a high dose rate in a short period and thus allowing the evaluation of the treatment response, through CT, FDG-PET or MRI, at shorter time interval compared to 90Y, usually\u0026thinsp;\u0026lt;\u0026thinsp;6 months in our clinical practice.\u003c/p\u003e \u003cp\u003eVarious prognostic staging systems have been developed for HCC, nevertheless the patients\u0026rsquo; performance status remains poorly touched [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Sarcopenia, defined as the \u0026ldquo;progressive loss of muscle mass and strength with a risk of adverse outcomes such as disability, poor quality of life and death\u0026rdquo; [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e], occurs relatively early in HCC disease and can independently negatively predict HCC related mortality in patients undergoing locoregional treatment [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. In fact, sarcopenia has been associated to lack of treatment response for HCC [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e], and lately it has been confirmed as a predictor of progressive disease in HCC treated also with TARE-90Y [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Because sarcopenia could be used to assess overall response of locoregional treatment of HCC [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e], specific population of patients with worsening sarcopenia should be carefully identified as these could benefit an early locoregional retreatment and a nutritional supportive strategy to restore muscle mass and strength.\u003c/p\u003e \u003cp\u003eThe aim of this study is to assess whether there is a potential relationship between changes in sarcopenia before and after one-three months of TARE-166Ho treatment and the rate of local response it induces, so to determine if the deterioration of sarcopenia worsening can serve as an early identificatory of a subset of patients who are at a high risk of disease progression.\u003c/p\u003e"},{"header":"MATERIAL AND METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\n\u003ch2\u003ePatients\u003c/h2\u003e\n\u003cp\u003eA retrospective investigation was conducted on 20 patients with HCC who underwent TARE-166Ho, between the period 2021\u0026ndash;2023. The analysis involved assessing the radiological response, according to mRECIST criteria, one and three months subsequent to the procedure. The local response rate was evaluated for all patients one month and three months after TARE procedure. The entire population was divided in two groups according to the delta value of the psoas muscle index (PMI) measured at the time of TARE, one-three months after TARE. The two groups were defined as follows: patients in which the delta PMI was stable or increased (No-Sarcopenia group; n\u0026thinsp;=\u0026thinsp;9) vs. patients in which the delta-PMI decreased (Sarcopenia group; n\u0026thinsp;=\u0026thinsp;7). The study was carried out in compliance with the guidelines of the Declaration of Helsinki, and this study was accepted by the local ethical committee.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\n\u003ch2\u003eTARE\u003c/h2\u003e\n\u003cp\u003eAll procedures were carried out by experienced interventional radiologists with more than five years of experience. For the treatment, 80\u0026ndash;170 MBq 166mHo-loaded scout microspheres were administered slowly through a 2.7-F micro-catheter (Progreat; Terumo Europe NV, Leuven, Belgium) placed in the pathological feeder artery. The distribution of the drug was assessed using SPECT imaging. Post-therapy SPECT/CT scans (Symbia IntevoTM system; Siemens, Erlangen, Germany) were performed between 1 and 20 hours after SIRT to evaluate the distribution of the microspheres thanks to 2D and 3D dosimetry maps.\u003c/p\u003e\n\u003cp\u003eFirstly, the accuracy and intensity of the 166Ho-microspheres activity distribution were evaluated by analyzing the 2D activity intensity peak (Pixel Value) of the signal along a line crossing the treated area. A higher peak indicated a more intense signal within the targeted area.\u003c/p\u003e\n\u003cp\u003eLater, the 3D effective dose in Gy distributed to the lesion and liver parenchyma per unit cumulated activity (GBq), was calculated according to the activity distribution obtained from SPECT/CT imaging, utilizing a MIM 6.1.7 workstation (MIM Software Inc., Cleveland, Ohio). For each patient, the mean absorbed dose (\u0026lt;\u0026thinsp;D\u0026gt;) in Gy for the normal liver and tumor were compared with the expected values (\u0026lt;\u0026thinsp;D\u0026thinsp;\u0026gt;\u0026thinsp;to tumor\u0026thinsp;\u0026gt;\u0026thinsp;100 Gy, \u0026lt;D\u0026thinsp;\u0026gt;\u0026thinsp;to normal liver\u0026thinsp;\u0026lt;\u0026thinsp;40 Gy) to assess the treatment efficacy.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\n\u003ch2\u003eSarcopenia measurement\u003c/h2\u003e\n\u003cp\u003eThe assessment of sarcopenia status was determined by measuring the PMI. The PMI was calculated using the following formula: PMI [mm/m^2]: [(minor diameter of left psoas\u0026thinsp;+\u0026thinsp;major diameter of left psoas\u0026thinsp;+\u0026thinsp;minor diameter of right psoas\u0026thinsp;+\u0026thinsp;major diameter of right psoas)/4]/height in m^2 [\u003cspan class=\"CitationRef\"\u003e17\u003c/span\u003e]. All the psoas measurements were performed at the level of L3-L4 (Figs.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e and \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\n\u003ch2\u003eStatistical analysis\u003c/h2\u003e\n\u003cp\u003eThe Mann\u0026ndash;Whitney U test was used for evaluating the delta-PMI according to treatment response at 1 and 3 months after TARE. The PMI at the time of TARE was compared with the PMI measurements at one and three months after TARE. The delta-PMI measurements between the first PMI measurement and the controls at one and three months were evaluated. Variables with a p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 were considered statistically significant.\u003c/p\u003e\n\u003cp\u003eThe accuracy of the different sarcopenia measurements performed over time was assessed through c-statistics analysis, with the intent to evaluate their ability to predict the progressive disease after TARE. Areas under the curve (AUCs) and 95% CI were reported. Fisher\u0026rsquo;s exact test was used for comparisons of categorical variables, respectively.\u003c/p\u003e\n\u003c/div\u003e"},{"header":"RESULTS","content":"\u003cp\u003eThe deltaPMI measured before (base value) and 1 month after TARE was evaluated after grouping response labels as follows: standard and progression disease were joined as the non-responder group and complete response or partial response were joined as the responder group.\u003c/p\u003e\n\u003cp\u003eNo statistically significant difference (p\u0026thinsp;=\u0026thinsp;0.229) was observed in terms of sarcopenia status, with a median deltaPMI of 0 vs. -0.44 in the responder and non-responder group, respectively (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\n\u003cp\u003eThe deltaPMI measured before (base value) and 3 months after TARE was also evaluated between the non-responder and responder group (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e). A statistically significant difference (p\u0026thinsp;=\u0026thinsp;0.041) was observed in terms of sarcopenia status, with a median deltaPMI of 0.12 vs. -0.57 in the responder and non-responder group, respectively.\u003c/p\u003e\n\u003cp\u003eA further Mann-Whitman test was conducted to investigate whether deltaPMI could be predictive of a response constant over time. For this purpose, a variable named \u003cem\u003ebestresp\u003c/em\u003e was introduced and defined as follows: if the response after one month is confirmed after three months and 0 otherwise.\u003c/p\u003e\n\u003cp\u003eNo statistically significant relevance (p\u0026thinsp;=\u0026thinsp;0.247) was observed for data collected one month after TARE, probably due to the fact that is premature to evaluate the radiological response to TARE treatment only one month after the procedure (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e\n\u003cp\u003eThe same analysis conducted 3 months after TARE showed that deltaPMI can be considered as a predictive biomarker of local response rate (p\u0026thinsp;=\u0026thinsp;0.028). In particular, we found out that a strong negative variation of PMI is associated with a poor response to treatment with a median deltaPMI of -0.57 in the non-responder and 0.12 in the responder group, respectively (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e6\u003c/span\u003e). It was interesting to note that the diagnostic ability for stable or progressive disease of the sarcopenia measurement increased with time after the TARE procedure.\u003c/p\u003e\n\u003cp\u003eThe ROC analysis was also used to investigate the optimal cut-off of deltaPMI that is statistically relevant in the prediction of a bestresp (i.e. a response to treatment constant over time).\u003c/p\u003e\n\u003cp\u003eAt three months, the deltaPMI value had an AUC\u0026thinsp;=\u0026thinsp;0.875 (p\u0026thinsp;=\u0026thinsp;0.0001, CIs 0.617 to 0.984). In particular, a PMI variation greater than \u0026minus;\u0026thinsp;0.293 resulted to be associated with a bestresp.\u003c/p\u003e\n\u003cp\u003eThis seems to confirm that a small deltaPMI variation is predictive of a good treatment. In fact, all 9 patients (100%) who showed a PMI variation greater than the cut-off had a good response to treatment (Fisher\u0026rsquo;s exact test, p\u0026thinsp;=\u0026thinsp;0.019).\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eSarcopenia deterioration at three months after TARE treatment with Holmium-166 is a reliable predictor of worse loco-regional response rate, in HCC patients.\u003c/p\u003e \u003cp\u003eSarcopenia has functioned as a predictive element across various clinical scenarios. It has been employed as a predictive factor among patients with HCC [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e], including patients undergoing Sorafenib [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e], intra-arterial chemoembolization [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e], and pre- or post-transplant [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Recently, sarcopenia worsening after TARE treatment with Yttrium-90 has been associated with progressive disease in the early stages [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe most recent Holmium-166 radionuclide has been established as a valid alternative to Yttrium-90 in TARE, also in consideration of the advantages it manifests. The analysis conducted at the three-month mark post-TARE-166Ho revealed that the difference in PMI, before and after the procedure, holds potential as a predictive biomarker of the local response rate (p\u0026thinsp;=\u0026thinsp;0.028). Notably, our findings indicated a negative shift in PMI correlated with an unfavorable treatment response, as evidenced by a median deltaPMI of -0.57 in the non-responder group, compared to a median value of 0.12 in the responder cohort (p\u0026thinsp;=\u0026thinsp;0.041). It was observed that the diagnostic efficacy of sarcopenia measurement in discerning stable or progressive disease displayed an augmenting trend over time, from one to three months, subsequent to the TARE procedure.\u003c/p\u003e \u003cp\u003eThis highlights the strength of sarcopenia measurement in predicting effectively the intermediate local outcome, after TARE-166Ho. As such, sarcopenia worsening is correlated with a worse mRECIST score in the intermediate stage. Furthermore, this approach was consistent among both males and females, regardless of the initial morphological differences that existed between the two genders.\u003c/p\u003e \u003cp\u003eConversely, no statistically significant PMI differences at one month after procedure was observed in both groups, likely attributable to the premature nature of assessing the radiological response to TARE treatment within just one month after the procedure. Moreover, the pre-procedural assessment of sarcopenia status exhibited no statistically significant distinctions between the cohort of patients experiencing progressive disease and those achieving complete response, partial response, or stable disease. This implies that the initial evaluation of sarcopenia cannot serve as a reliable predictor for unfavorable oncological outcomes following transarterial radioembolization.\u003c/p\u003e \u003cp\u003eThe assessment of TARE treatment response has been evaluated through CT and MRI, or FDG-PET scans. However, these techniques necessitate a minimum of three months to furnish accurate insights into TARE outcomes [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn addition to what previously published illustrating the association between sarcopenia worsening and HCC progression at 1 and 3 months after TARE-90Y, this study confirms the same outcomes utilizing Holmium-166.\u003c/p\u003e \u003cp\u003eThe divergence in sarcopenia status, evidenced three months post-procedure through routinely conducted multiphasic CT scans, presents a convenient non-invasive predictive biomarker for treatment efficacy, confirming the association of skeletal muscle depletion in predicting worse loco-regional response rate. Patients could benefit from early skeletal muscle depletion adjustment by simple non-invasive methods that would aid in the clinical management by reducing the probability of disease progression, according to these data.\u003c/p\u003e \u003cp\u003eSwift identification of declining sarcopenia could prompt the implementation of aggressive support protocols. Multimodal approaches encompassing nutritional support, physical therapy, and medications such as ibuprofen (Menac trial) and selective androgen receptor modulators and ghrelin receptor activation with agonists, are recognized as foundational in managing sarcopenia. Interestingly, the initial sarcopenic status could guide the selection of a subset of HCC patients undergoing TARE as a preparatory measure for liver transplant. As such, sarcopenia status could aid in identifying individuals with predictable positive outcomes following transplantation and that would mostly benefit from it. On the other end of the spectrum, the prompt identification of patients at risk of non-responsiveness could offer utility by guiding the early implementation of systemic therapies. Furthermore, the potential for sarcopenia status to forecast disease progression could aid in identifying candidates for early TARE retreatment. In fact, retreatment discussions cases where patients tolerated the initial procedure without substantial improvement, often not accounting for the necessary CT/MRI assessment time-frame, although there is no consensus regarding the optimal timing for retreatment.\u003c/p\u003e \u003cp\u003eThe study has several limitations that need discussion. Foremost, the retrospective nature of the study design precludes the establishment of a randomized framework, which may influence the generalizability of the findings. Secondly, the sample size under analysis was relatively modest, thus these results must be validated by further studies with larger population size. The future trajectory of research would ideally encompass both larger retrospective studies, but more notably, prospective and randomized studies to confirm and further validate these results.\u003c/p\u003e"},{"header":"CONCLUSIONS","content":"\u003cp\u003e TARE treatment is now a firmly established therapeutic option for patients dealing with locally advanced hepatocellular carcinoma, more recently Holmium-166 has opened new horizons in this population thanks to various advantages it fosters.\u003c/p\u003e \u003cp\u003eNonetheless, assessing the response to TARE treatment during the initial stages of follow-up is often challenging. Sarcopenia deterioration is a reliable predictor of worse local response rate at three months after TARE-166Ho, and could serve as a valuable indicator for identifying patients who are at a heightened risk of disease progression. In fact, PMI decreased significantly more in the group of poor responders. Should our findings be substantiated, they could play a pivotal role in the early identification of patients who do not respond to the treatment and whom may benefit from prompt integrative restorative treatment.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eAcknowledgements:\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003eFunding:\u003c/p\u003e\n\u003cp\u003eThis research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\n\u003cp\u003eCompeting Interests:\u003c/p\u003e\n\u003cp\u003eThe authors have no relevant financial or non-financial interests to disclose.\u003c/p\u003e\n\u003cp\u003eAuthor Contributions:\u003c/p\u003e\n\u003cp\u003eAll authors made substantial contributions in conception and design of the article, acquisition, analysis and interpretation of data, drafting of the article and final approval of the version to be published. CT, GV, LT were responsible for conceptualization. NU, SU were responsible for data curation. GV were responsible for project administration. CT, NU were responsible for writing-original draft. SU was responsible for formal analysis and methodology. NU, CT were responsible for writing\u0026mdash;review \u0026amp; editing. GV, FC were responsible for supervision.\u003c/p\u003e\n\u003cp\u003eData Availability:\u003c/p\u003e\n\u003cp\u003eThe datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003eConsent to participate:\u003c/p\u003e\n\u003cp\u003eInformed consent was obtained from all individual participants included in the study.\u003c/p\u003e\n\u003cp\u003eConsent for publication:\u003c/p\u003e\n\u003cp\u003eThe authors affirm that human research participants provided informed consent for publication of the images in Figure(s) 1-6.\u003c/p\u003e\n\u003cp\u003eEthics approval:\u003c/p\u003e\n\u003cp\u003eThis is an observational retrospective study and the Ethical Committee Lazio Area 5 evaluated this research study under the registral sperimental number N. 1561/21.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eOh JH, Jun DW. 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TARE in Hepatocellular Carcinoma: From the Right to the Left of BCLC. \u003cem\u003eCardiovasc Intervent Radiol\u003c/em\u003e. 2022;45(11):1599-1607. doi:10.1007/s00270-022-03072-8\u003c/li\u003e\n\u003cli\u003eDhondt E, Lambert B, Hermie L, et al. 90Y Radioembolization versus Drug-eluting Bead Chemoembolization for Unresectable Hepatocellular Carcinoma: Results from the TRACE Phase II Randomized Controlled Trial. \u003cem\u003eRadiology\u003c/em\u003e. 2022;303(3):699-710. doi:10.1148/radiol.211806\u003c/li\u003e\n\u003cli\u003eKulik LM, Carr BI, Mulcahy MF, et al. Safety and efficacy of 90Y radiotherapy for hepatocellular carcinoma with and without portal vein thrombosis. \u003cem\u003eHepatology\u003c/em\u003e. 2008;47(1):71-81. doi:10.1002/hep.21980\u003c/li\u003e\n\u003cli\u003eEl Fouly A, Ertle J, El Dorry A, et al. 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MRI-based biodistribution assessment of holmium-166 poly(L-lactic acid) microspheres after radioembolisation. \u003cem\u003eEur Radiol\u003c/em\u003e. 2013;23(3):827-835. doi:10.1007/s00330-012-2648-2\u003c/li\u003e\n\u003cli\u003ePerisetti A, Goyal H, Yendala R, Chandan S, Tharian B, Thandassery RB. Sarcopenia in hepatocellular carcinoma: Current knowledge and future directions. \u003cem\u003eWorld J Gastroenterol\u003c/em\u003e. 2022;28(4):432-448. doi:10.3748/wjg.v28.i4.432\u003c/li\u003e\n\u003cli\u003ePalazzoadriano M, Albano V, Bellanca L, Latteri S, Valdes L, Mangiameli S. Modifications induced in the renin-angiotensin-aldo-sterone system of rats by alpha-blocking drugs. \u003cem\u003ePharmacol Res Commun\u003c/em\u003e. 1978;10(10):925-937. doi:10.1016/s0031-6989(78)80083-6\u003c/li\u003e\n\u003cli\u003eVallati GE, Trobiani C, Teodoli L, et al. Sarcopenia Worsening One Month after Transarterial Radioembolization Predicts Progressive Disease in Patients with Advanced Hepatocellular Carcinoma. \u003cem\u003eBiology (Basel)\u003c/em\u003e. 2021;10(8):728. doi:10.3390/biology10080728\u003c/li\u003e\n\u003cli\u003eBadran H, Elsabaawy MM, Ragab A, Aly RA, Alsebaey A, Sabry A. Baseline Sarcopenia is Associated with Lack of Response to Therapy, Liver Decompensation and High Mortality in Hepatocellular Carcinoma Patients. \u003cem\u003eAsian Pac J Cancer Prev\u003c/em\u003e. 2020;21(11):3285-3290. doi:10.31557/APJCP.2020.21.11.3285\u003c/li\u003e\n\u003cli\u003eXu L, Jing Y, Zhao C, et al. 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Association between Loss of Skeletal Muscle Mass and Mortality and Tumor Recurrence in Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis. \u003cem\u003eLiver Cancer\u003c/em\u003e. 2018;7(1):90-103. doi:10.1159/000484950\u003c/li\u003e\n\u003cli\u003eTakada H, Kurosaki M, Nakanishi H, et al. Impact of pre-sarcopenia in sorafenib treatment for advanced hepatocellular carcinoma. \u003cem\u003ePLoS One\u003c/em\u003e. 2018;13(6):e0198812. doi:10.1371/journal.pone.0198812\u003c/li\u003e\n\u003cli\u003eYamashima M, Miyaaki H, Honda T, et al. Significance of psoas muscle thickness as an indicator of muscle atrophy in patients with hepatocellular carcinoma treated with sorafenib. \u003cem\u003eMol Clin Oncol\u003c/em\u003e. 2017;7(3):449-453. doi:10.3892/mco.2017.1321\u003c/li\u003e\n\u003cli\u003eAhmadzadehfar H, Duan H, Haug AR, Walrand S, Hoffmann M. The role of SPECT/CT in radioembolization of liver tumours. \u003cem\u003eEur J Nucl Med Mol Imaging\u003c/em\u003e. 2014;41 Suppl 1:S115-124. doi:10.1007/s00259-013-2675-5\u003c/li\u003e\n\u003cli\u003eAdcock CS, Florez E, Zand KA, Patel A, Howard CM, Fatemi A. Assessment of Treatment Response Following Yttrium-90 Transarterial Radioembolization of Liver Malignancies. \u003cem\u003eCureus\u003c/em\u003e. 2018;10(6):e2895. doi:10.7759/cureus.2895\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"TARE, Sarcopenia, HCC, Interventional Oncology, Liver, Holmium-166","lastPublishedDoi":"10.21203/rs.3.rs-3429080/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3429080/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003ePurpose:\u003c/p\u003e\n\u003cp\u003eTo investigate the association between changes in sarcopenia before and after one-three months of Transarterial Radioembolization (TARE) treatment with Holmium-166 (166Ho) for hepatocellular carcinoma (HCC) and its impact on the rate of local response.\u003c/p\u003e\n\u003cp\u003eMethods:\u003c/p\u003e\n\u003cp\u003eA retrospective single center analysis was conducted on 20 HCC patients who underwent 166Ho-TARE. Patients were categorized into two groups based on the change in psoas muscle index (PMI) measured at the time of TARE and one-three months after: No-Sarcopenia group (deltaPMI stable or increased; n = 9) and Sarcopenia group (deltaPMI decreased; n = 7). DeltaPMI was associated to the local response rate, according to mRECIST criteria.\u003c/p\u003e\n\u003cp\u003eResults:\u003c/p\u003e\n\u003cp\u003eDeltaPMI was evaluated according to mRECIST criteria: non-responder group (standard and progression disease) and responder group (complete response or partial response).\u003c/p\u003e\n\u003cp\u003eThree months after TARE, a significant difference in sarcopenia status was observed (p = 0.041), with a median deltaPMI of -0.57 in the non-responder and 0.12 in the responder group. DeltaPMI measured three months after TARE can be considered as a predictive biomarker of the local response rate (p=0.028).\u003c/p\u003e\n\u003cp\u003eConclusion:\u003c/p\u003e\n\u003cp\u003eSarcopenia deterioration at three months from TARE with Holmium-166 is a reliable predictor of worse loco-regional response rate, evaluated radiologically, in HCC patients.\u003c/p\u003e","manuscriptTitle":"Sarcopenia worsening after transarterial radioembolization with Holmium-166 predicts progressive disease in patients with advanced hepatocellular carcinoma.","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2023-10-30 19:55:03","doi":"10.21203/rs.3.rs-3429080/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"f6d836ce-8839-4b36-8ec7-a9a3cf0e27e7","owner":[],"postedDate":"October 30th, 2023","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":25768910,"name":"Health sciences/Biomarkers"},{"id":25768911,"name":"Health sciences/Oncology"}],"tags":[],"updatedAt":"2024-01-16T10:29:27+00:00","versionOfRecord":[],"versionCreatedAt":"2023-10-30 19:55:03","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3429080","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3429080","identity":"rs-3429080","version":["v1"]},"buildId":"WrCJVZZCHTDjtuVLN7oU0","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}