Locoregional Therapy Research Articles

LI-RADS Nonradiation Treatment Response Algorithm Version 2024: Diagnostic Performance and Impact of Ancillary Features.

Background: LI-RADS Treatment Response Algorithm (TRA) version 2024 (v2024) introduced separate algorithms for detecting hepatocellular carcinoma (HCC) viability after radiation and nonradiation locoregional therapies (LRT). The nonradiation algorithm incorporated MRI-based ancillary features to optionally upgrade lesions from LR-TR Equivocal to LR-TR Viable. Objective: To compare the diagnostic performance of LI-RADS Nonradiation TRA v2024 with LI-RADS TRA version 2017 (v2017) and modified RECIST (mRECIST) for evaluating HCC response to LRT on MRI, with attention to the impact of ancillary features. Methods: This retrospective study included 231 patients (198 male, 33 female; median age, 56 years) who underwent LRT for HCC followed by liver resection or transplant between January 2017 and December 2022. Two radiologists (R1, R2) independently evaluated treated lesions (n=306) using LI-RADS Nonradiation TRA v2024, LI-RADS TRA v2017, and mRECIST. Lesions were classified as showing pathologic viability (n=249) or complete pathologic necrosis (n=57) based on curative surgery pathology. Diagnostic performance for pathologic viability was compared using Bonferroni-adjusted McNemar tests, classifying LR-TR Equivocal assessments as test negative. Results: Sensitivity, specificity, and accuracy for LI-RADS Nonradiation TRA v2024 with ancillary features were 85.5%, 75.4%, and 83.7% (R1), and 87.2%, 63.2%, and 82.7% (R2); for LI-RADS Nonradiation TRA v2024 without ancillary features were 81.1%, 78.9%, and 80.7% (R1), and 80.3%, 78.9%, and 80.1% (R2); for LI-RADS TRA v2017 were 79.9%, 82.5%, and 80.4% (R1), and 79.1%, 79.0%, and 79.1% (R2); and for mRECIST, were 83.9%, 54.4%, and 78.4% (R1), and 78.2%, 40.4%, and 78.4% (R2). LI-RADS Nonradiation TRA v2024 with ancillary features showed higher sensitivity and accuracy than LI-RADS Nonradiation v2024 without ancillary features (both readers); higher sensitivity than LI-RADS TRA v2017 (both readers); higher specificity than mRECIST (both readers); and higher accuracy than LI-RADS TRA v2017 (R2) (p<.008); remaining comparisons between LI-RADS Nonradiation TRA v2024 with ancillary features and other systems were not significant (p>.008). Conclusion: LI-RADS Nonradiation TRA v2024 showed good diagnostic performance in detecting pathologic viability. Ancillary features yielded improved sensitivity and accuracy without significant change in specificity. Clinical Impact: Use of LI-RADS Nonradiation TRA v2024 with ancillary features is recommended for guiding prognostic assessments and treatment decisions after LRT.

Multi-task Bayesian model combining FDG-PET/CT imaging and clinical data for interpretable high-grade prostate cancer prognosis.

We propose a fully automatic multi-task Bayesian model, named Bayesian Sequential Network(BSN), for predicting high-grade(Gleason 8) prostate cancer(PCa) prognosis using pre-prostatectomy FDG-PET/CT images and clinical data. BSN performs one classification task and five survival tasks: predicting lymph node invasion (LNI), biochemical recurrence-free survival (BCR-FS), metastasis-free survival, definitive androgen deprivation therapy-free survival, castration-resistant PCa-free survival, and PCa-specific survival(PCSS). Experiments are conducted using a dataset of 295patients. BSN outperforms widely used nomograms on all tasks except PCSS, leveraging multi-task learning and imaging data. BSN also provides automated prostate segmentation, uncertainty quantification, personalized feature-based explanations, and introduces dynamic predictions, a novel approach that relies on short-term outcomes to refine long-term prognosis. Overall, BSN shows great promise in its ability to exploit imaging and clinicopathological data to predict poor outcome patients that need treatment intensification with loco-regional or systemic adjuvant therapy for high-risk PCa.

Leveraging long-acting IL-15 agonists for intratumoral delivery and enhanced antimetastatic activity

IntroductionIL-15 agonists hold promise as immunotherapeutics due to their ability to induce the proliferation and expansion of cytotoxic immune cells including natural killer (NK) and CD8+ T cells. However, they generally have short half-lives that necessitate frequent administration to achieve efficacy. To address this limitation, we have developed a half-life extension technology using hydrogel microspheres (MS). Here, the therapeutic is tethered to MSs by a releasable linker with pre-programed cleavage rates. We previously showed the MS conjugate of single-chain IL-15, MS~IL-15, effectively increased the half-life of IL-15 to approximately 1 week and enhanced the pharmacodynamics. We sought to determine whether the same would be true with a MS conjugate of the IL-15 agonist, receptor-linker IL-15 (RLI).MethodsWe prepared a long acting MS conjugate of RLI, MS~RLI. The pharmacokinetics and pharmacodynamics of MS~RLI were measured in C57BL/6J mice and compared to MS~IL-15. The antitumor efficacy of MS~RLI was measured when delivered subcutaneously or intratumorally in the CT26 tumor model and intratumorally in the orthotopic EO771 tumor model.ResultsMS~RLI exhibited a half-life of 30 h, longer than most IL-15 agonists but shorter than MS~IL-15. The shorter than expected half-life of MS~RLI was shown to be due to target-mediated-disposition caused by an IL-15 induced cytokine sink. MS~RLI resulted in very potent stimulation of NK and CD44hiCD8+ T cells, but also caused significant injection-site toxicity that may preclude subcutaneous administration. We thus pivoted our efforts toward studying the MS~RLI for long-acting intra-tumoral therapy, where some degree of necrosis might be beneficial. When delivered intra- tumorally, both MS~IL-15 and MS~RLI had modest anti-tumor efficacy, but high anti- metastatic activity.ConclusionIntra-tumoral MS~RLI and MS~RLI combined with systemic treatment with other agents could provide beneficial antitumor and anti-metastatic effects without the toxic effects of systemic IL-15 agonists. Our findings demonstrate that intra-tumorally administered long-acting IL-15 agonists counter two criticisms of loco-regional therapy: the necessity for frequent injections and the challenge of managing metastases.

Use of albumin and CRP related immuno-nutritional markers for prediction of locoregional response to treatment in unresectable hepatocellular carcinoma

Objective:We analysed the relationship between albumin and CRP related inflammation markers (Controlling nutritional status(Conut)score, lymphocyte albumin factor(LA), albumin-bilirubin score (ALBI), highly sensitive modified Glasgow prognostic score (Hs-mGPS), Glasgow prognostic score(GPS)) and locoregional treatment response in HCC. Materials and methods:Among 180 HCC patients, 63 patients who underwent locoregional therapy were included in this study. Albumin and CRP related immuno-nutrition scores were calculated by recording routine laboratory tests between the fourth and eighth week after treatment. The predictive and prognostic value of these markers for overall survival(OS) and disease free survival after treatment(DFS) were analysed. Results:The mean age was 63 years (min-max:26-87) and 59 (93.7%) of the patients were male. The mean follow up period was 25 months and 53 patients were deceased (84.1%). mOS: 18.56 months (min-max: 13.13-23.99); mDFS: 7 months (min-max: 3.63-10.37) after locoregional treatment. Cut-off values of prognostic markers were determined by Roc analysis. Statistically significant correlation was found between age(p=0.019), Conut(p=0.001), GPS(p=0.028), Hs-mGPS(p=0.012), LA(p=0.017) and ALBI(p=0.002) and mOS. The relationship between Conut(p=0.002), GPS(p

Inter-reader agreement of LI-RADS treatment response algorithm among three readers with different seniorities for hepatocellular carcinoma after locoregional therapy.

The accurate evaluation of tumor response after locoregional therapy is crucial for adjusting therapeutic strategy and guiding individualized follow-up. To determine the inter-reader agreement of the LR-TR algorithm for hepatocellular carcinoma treated with locoregional therapy among radiologists with different seniority. A total of 275 treated observations on 249 MRI scans from 99 patients were retrospectively collected. Three readers of different seniorities (senior, intermediate, and junior with 10, 6, and 2 years of experience in hepatic imaging, respectively) analyzed the presence or absence of features (arterial-phase hyperenhancement and washout) and evaluated LR-TR category. There were substantial inter-reader agreements for overall LR-TR categorization (kappa = 0.704), LR-TR viable (kappa = 0.715), and LR-TR non-viable (kappa = 0.737), but fair inter-reader agreement for LR-TR equivocal (kappa = 0.231) among three readers. The inter-reader agreement was substantial for arterial-phase hyperenhancement (kappa = 0.725), but moderate for washout (kappa = 0.443) among three readers. The inter-reader agreements between two readers were substantial for overall LR-TR categorization (kappa = 0.734, 0.727, 0.652), LR-TR viable (kappa = 0.719, 0.752, 0.678), and LR-TR non-viable (kappa = 0.758, 0.760, 0.694), which were at the same level as the inter-reader agreements among three readers. In addition, the inter-reader agreements between two readers were substantial for arterial-phase hyperenhancement (kappa = 0.733, 0.766, 0.678), but moderate for washout (kappa = 0.473, 0.422, 0.446), which were at the same level as the inter-reader agreements among three readers. LR-TR algorithm demonstrated overall substantial inter-reader agreement among radiologists with different seniority.

Three-dimensional dynamics of mesothelin-targeted CAR.CIK lymphocytes against ovarian cancer peritoneal carcinomatosis

Intraperitoneal cellular immunotherapy with CAR-redirected lymphocytes is an intriguing approach to target peritoneal carcinomatosis (PC) from ovarian cancer (OC), which is currently evaluated in clinical trials. PC displays a composite structure with floating tumor cells within ascites and solid-like masses invading the peritoneum. Therefore, a comprehensive experimental model is crucial to optimize CAR-cell therapies in such a peculiar environment. Here, we explored the activity of cytokine-induced killer lymphocytes (CIK), redirected by CAR against mesothelin (MSLN-CAR.CIK), within reductionistic 3D models resembling the structural complexity of both liquid and solid components of PC. MSLN-CAR.CIK effectively killed and were functionally efficient against OC targets. In a “floating-like” 3D context with floating OC spheroids, both tumor localization and killing by MSLN-CAR.CIK were significantly boosted by fluid flow. In a “solid-like” context, MSLN-CAR.CIK were recruited through the extracellular matrix on embedded tumor aggregates, with variable kinetics depending on the effector-target distance. Furthermore, MSLN-CAR.CIK penetrated the inner levels of OC spheroids exerting effective tumor killing. Our findings provide currently unknown therapeutically relevant information on intraperitoneal approaches with CAR.CIK, supporting further developments and improvements for clinical studies in the context of locoregional cell therapy approaches for patients with PC from OC.

Silk fibroin nanoparticles for locoregional cancer therapy: Preliminary biodistribution in a murine model and microfluidic GMP-like production

Silk fibroin nanoparticles (SFNs) have been widely investigated for drug delivery, but their clinical application still faces technical (large-scale and GMP-compliant manufacturing), economic (cost-effectiveness in comparison to other polymer-based nanoparticles), and biological (biodistribution assessments) challenges. To address biodistribution challenge, we provide a straightforward desolvation method (in acetone) to produce homogeneous SFNs incorporating increasing amounts of Fe2O3 (SFNs-Fe), detectable by Magnetic Resonance Imaging (MRI), and loaded with curcumin as a model lipophilic drug. SFNs-Fe were characterized by a homogeneous distribution of the combined materials and showed an actual Fe2O3 loading close to the theoretical one. The amount of Fe2O3 incorporated affected the physical-chemical properties of SFNs-Fe, such as polymer matrix compactness, mean diameter and drug release mechanism. All formulations were cytocompatible; curcumin encapsulation mitigated its cytotoxicity, and iron oxide incorporation did not impact cell metabolic activity but affected cellular uptake in vitro. SFNs-Fe proved optimal for biodistribution studies, as MRI showed significant nanoparticle retention at the administration site, supporting their potential for locoregional cancer therapy. Finally, technical and economic challenges in SFN production were overcome using a GMP-compliant microfluidic scalable technology, which optimized preparation to produce smaller particle sizes compared to manual methods and reduced acetone usage, thus offering environmental and economic benefits. Moreover, enabling large-scale production of GMP-like SFNs, this represents a considerable step forward for their application in the clinic.

Therapeutic advances in hepatocellular carcinoma: an update from the 2024 ASCO annual meeting.

Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related deaths worldwide. Recent advances in immunotherapies, targeted therapies, and combination treatments have significantly improved outcomes for many patients with HCC. This review summarizes key findings from the 2024 ASCO Annual Meeting, focusing on emerging therapies, including immune checkpoint inhibitors (ICIs), CAR-T cell therapies, oncolytic viruses, and locoregional treatments like transarterial chemoembolization (TACE) and hepatic arterial infusion chemotherapy (HAIC). ICIs, particularly when combined with other agents, have shown promising efficacy, though challenges such as immune-related adverse events and resistance mechanisms remain. CAR-T cell therapies and oncolytic viruses offer novel therapeutic avenues for advanced HCC, but their long-term efficacy in solid tumors is still under investigation. Locoregional therapies, especially in combination with systemic treatments, continue to play a critical role in managing unresectable HCC and improving conversion rates to surgical resection. Additionally, the potential of biomarkers, such as hypoxia scores and CTNNB1 mutations, is being explored to better personalize treatment and predict patient responses. These biomarkers could pave the way for more targeted and effective therapeutic strategies. Overall, the recent studies presented at the ASCO meeting highlight progress in HCC treatment, underscoring the importance of continued innovation. Future research should focus on overcoming resistance mechanisms, optimizing combination therapies, and integrating biomarker-driven approaches to improve patient outcomes and enhance personalized treatment strategies.

Surgical and oncological outcome after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal mesothelioma : Aretrospective single center experience.

Peritoneal mesothelioma (PM) is arare disease with various histopathological subtypes. For malignant peritoneal mesothelioma and borderline subgroups locoregional therapy with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has been implemented. The aim of our study was to retrospectively present the outcome after CRS and HIPEC for patients with different subtypes of peritoneal mesothelioma. In total 15patients received CRS and HIPEC due to peritoneal mesothelioma at our tertiary referral hospital between 2013 and 2022. Surgical and oncologic outcomes of 14 of those patients were retrospectively evaluated as one patient was lost to follow-up. The cohort consisted of 9patients with diffuse malignant peritoneal mesothelioma (64.3%), 3patients with multicystic peritoneal mesothelioma (21.4%) and 2patients with well-differentiated peritoneal mesothelioma (14.3%). Complete cytoreduction was possible in 85.7% (n = 12). The major complication rate was 28.6% (n = 4) and the reoperation rate was 14.3% (n = 2). Median follow-up was 55months (standard error, SE 15.0%, 95% confidence interval, CI 25.6-84.4 months). Over this time period 64.3% (n = 9) had no evidence of disease, 21.4% (n = 3) were alive with disease and 14.3% (n = 2) died of peritoneal mesothelioma. The median recurrence-free survival of patients was 13months (SE13.0%, 95% CI 0.0-32.2 months). None of the patients with multicystic peritoneal mesothelioma had evidence of disease at the time of last follow-up. Patients with peritoneal mesothelioma should receive locoregional treatment as good oncological results can be achieved with reasonable postoperative morbidity. Thus, awareness is necessary for this rare but potentially aggressive disease to offer the best medical care.

Hepatocellular carcinoma

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

Tumor ablation in children.

Tumor ablation represents an increasingly important topic in pediatric interventional radiology. Many ablative techniques are well known and established in the adult population, and the adoption of these techniques in the pediatric field is increasing. Image-guided tumor ablation represents a wide category of interventional radiology procedures that can be applied to both benign and malignant pediatric solid tumors. Tumor ablation, either alone or in combination with locoregional therapy, can have curative, debulking, or palliative effects on a wide variety of histological tumor types.

Locoregional Therapies and Interventional Radiology in Managing Hepatocellular Carcinoma: A Comprehensive Approach to Bridging, Downstaging, and Liver Transplantation

AbstractHepatocellular carcinoma (HCC) remains a significant global health challenge, particularly for patients awaiting liver transplants (LTs) due to the scarcity of donor organs. During the waiting period, a multidisciplinary approach becomes crucial to optimize tumor treatment and preserve liver function. In recent years, interventional radiology has emerged as an integral part of treatment strategies. It has played a pivotal role in bridging and downstaging patients on the path to transplantation. Interventional radiologists administer minimally invasive locoregional therapies to HCC patients on LT waiting lists. Additionally, they address complications such as portal hypertension and portal vein thrombosis, which can lead to clinical deterioration and jeopardize transplant candidacy. This article examines the pivotal role of interventional radiology in the management of HCC, highlighting recent studies and advancements within the field. Additionally, it provides a concise review of the eligibility criteria for LT in patients with HCC, alongside a discussion of the surgical techniques employed in LT for these patients.

Chinese Expert Consensus on the Combination of Targeted Therapy and Immunotherapy with Locoregional Therapy for Intermediate/Advanced Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is a major cause of cancer-related mortality, it ranks as the second most common cause of cancer deaths in China. Most HCC patients are first diagnosed at an advanced stage. In recent years, targeted therapy combined with immunotherapy has become the preferred regimen for systemic treatment of intermediate-advanced HCC, while targeted therapy combined with immunotherapy plus local treatment could further improve the efficacy in many clinical studies. To better guide the clinical treatment for effective and safe combination therapy, our interdisciplinary panel on the treatment of intermediate-advanced HCC comprising hepatologists, hepatobiliary surgeons, oncologists, radiologists, interventional radiologists and traditional Chinese medicine physicians have formulated this consensus based on current clinical studies and clinical medication experience for reference. The consensus contained 15 recommendations, including the applicable population and management, local treatment selection, conversion strategy, treatment strategy after tumor progression and management of common adverse reactions.

Chemoembolization, Radioembolization, and Percutaneous Ablation: New Opportunities for Treating Ovarian Cancer Liver Metastasis.

Parenchymal liver metastases from ovarian cancer, occurring in 2-12.5% of cases, significantly worsen prognosis. While surgery and systemic treatments remain primary options, unresectable or chemotherapy-resistant multiple liver metastases pose a significant challenge. Recent advances in liver-directed therapies, including radiofrequency ablation, microwave ablation, cryoablation, transarterial chemoembolization (TACE), and radioembolization, offer potential treatment alternatives. However, the efficacy of these techniques is limited by factors such as tumor size, number, and location. The ideal candidate for tumor ablation is a patient with paucifocal disease, a single tumor up to 5cm or up to 3 tumors smaller than 3cm and tumors 1cm away from major bile ducts and high-flow vessels. Transarterial chemoembolization could be performed in patients with less than 70% tumor load. Differently, radioembolization is available with less limitation on the sites or number of liver cancers. Radioembolization techniques are also able to downsize liver metastases. However, there are limited data regarding the outcomes of loco-regional therapy in patients with hepatic metastases from ovarian cancer. Advancing liver-directed therapies through interventional oncology, combined with robust data on the oncological efficacy of these local treatments, will validate their potential as effective locoregional therapies for liver metastases. This could offer a promising treatment option for patients with ovarian cancer and unresectable hepatic metastases.

LI-RADS radiation-based treatment response algorithm for HCC: what to know and how to use it.

Locoregional treatments (LRT) continue to advance for hepatocellular carcinoma (HCC). Selective internal radiation therapy (SIRT) or transarterial radioembolization (TARE) with radioactive 90 Yttrium (Y90) microspheres is currently widely accepted, and external beam and stereotactic body radiation (EBRT/SBRT) are increasingly used as LRT1-5. Assessment of treatment response after these radiation-based therapies can be challenging, given that the adjacent liver also undergoes treatment related changes, inflammatory changes occur, and there is a variable time for response to develop. In 2017, the liver imaging reporting and data system (LI-RADS) workgroup initially developed a single algorithm for the imaging assessment of treatment response encompassing all types of locoregional therapies, the LI-RADS treatment response (LR-TR) algorithm. Recognizing that response and imaging patterns differ between radiation and non-radiation based therapies, the LR-TR working group recently updated the algorithm to reflect the unique characteristics of tumor response for therapies involving radiation. This article aims to elucidate the changes in the new version of the LI-RADS TR, with a guide for algorithm utilization and illustration of expected and unexpected findings post liver directed therapies for HCC.

Durvalumab-Induced Immune Thrombocytopenia in Patients with Advanced Cholangiocarcinoma Undergoing Yttrium-90 Radioembolization

Introduction: Immune thrombocytopenia (ITP) secondary to durvalumab, a programmed cell death ligand 1 inhibitor, is a rare but clinically significant immune-related adverse event. Herein, we present 2 patients with cholangiocarcinoma who developed ITP immediately post-yttrium-90 radioembolization (Y90-RE) while on durvalumab-based systemic therapy. We hypothesize that given the timing, the immunotherapy and the radioembolization combination led to this event. It is not uncommon given the approval of immunotherapy and its role in locoregional therapies, that patients are treated with a combination of systemic immunotherapy and radioembolization or other forms of radiation, thus signifying the importance of potential complications. Case Presentation: Two patients, a 67-year-old female and a 60-year-old man, with biopsy-proven advanced unresectable cholangiocarcinoma, received a combination of systemic therapy with durvalumab, gemcitabine, and cisplatin and subsequently Y90-RE. Both patients developed ITP following in the immediate post-Y90-RE period. All other causes of ITP were comprehensively ruled out and treatment for ITP was initiated in the form of high-dose steroid and intravenous immunoglobulins. Durvalumab was discontinued, and only gemcitabine/cisplatin-based chemotherapy was continued thereafter. Due to recurrence, one of the patients required longer courses of steroids as well as thrombopoietin receptor agonists. Conclusion: Immunotherapy in the form of durvalumab and now pembrolizumab alongside chemotherapy is an approved first-line standard of care. Furthermore, it is not uncommon for patients to receive Y90-RE to improve patient outcomes. This report highlights the development of ITP in 2 patients who received durvalumab alongside Y90-RE. Awareness of this as a potential immune-mediated event is important to allow for close monitoring of platelet counts and for early intervention/management when this occurs.

Translational Relevance and Future Integration of the Oncopig Cancer Model in Preclinical Applications.

Porcine cancer models offer a valuable platform for evaluating interventions such as devices, surgeries, and locoregional therapies, which are often challenging to test in mouse models. In addition to size and anatomical similarities with humans, pigs share greater similarities in genetics, immunity, drug metabolism, and metabolic rate with humans as compared to mouse models, increasing their translational relevance. This review focuses on the Oncopig Cancer Model, a genetically engineered porcine model designed to recapitulate human cancer. Harboring a transgenic cassette that expresses oncogenic mutant KRAS and TP53 under control of a Cre-Lox system, the Oncopig allows temporal and spatial control of tumor induction. Its versatility has enabled the development of diverse cancer models including liver, pancreatic, lung, and bladder cancer. Serving as a clinically relevant model for human cancer, the Oncopig addresses unmet clinical needs and holds immense promise for advancing preclinical cancer research and therapeutic development.

Association of adverse events and quality of life in patients with unresectable hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the third-leading cause of cancer-related deaths globally. Patients are often diagnosed with advanced disease, in which systemic and locoregional therapies are commonly used as first-line treatment. Such treatments can cause adverse events (AEs) that negatively affect quality of life (QoL), which is particularly undesirable where prognosis is poor. The aim of the present study was to evaluate the impact of common AEs on QoL in patients with HCC. Data from the SARAH randomized controlled trial (RCT) were analyzed. Given the large number of distinct AEs that occurred in the trial, AEs were grouped as in the SARAH trial and prioritized using principal component analysis (PCA). Linear mixed-effects models were then applied with age, ECOG status, and AEs as predictors of the QoL change as measured with the EORTC Core Quality of Life Questionnaire (QLQ-C30). The PCA resulted in the selection of 28 AEs for inclusion in the linear mixed-effects models. Of the 28 AEs, diarrhea, decreased appetite, abdominal pain, and palmar-plantar erythrodysesthesia syndrome (hand-foot syndrome) were significant drivers of reductions in QoL as measured using the QLQ-C30 global health status scale. Diarrhea, abdominal pain, and hand-foot syndrome were also significant drivers of reduced QoL outcomes. The present analysis showed that diarrhea, decreased appetite, abdominal pain, and palmar-plantar erythrodysesthesia were significantly associated with reduced QoL in patients with unresectable HCC. Reducing the incidence and/or severity of these AEs should therefore be a key focus when selecting the optimal treatments for these patients.

Is DEB-TACE as locoregional therapy before liver transplantation for hepatocellular carcinoma effective?

BackgroundThe objectives were to assess the safety and efficacy of drug-eluting bead transarterial chemoembolization (DEB-TACE) as locoregional therapy (LRT) in hepatocellular carcinoma (HCC) before liver transplantation (LT) beyond Hangzhou criteria (HC) and to analyze the prognostic factors.MethodsForty patients with HCC beyond HC who received DEB-TACE only before LT were retrospectively analyzed between January 2017 and December 2022. Data on patient demographics, disease characteristics, treatment response, and adverse events (AE) were collected. Overall survival (OS) and recurrence-free survival (RFS) were evaluated with Kaplan-Meier curves. Univariate and multivariate Cox regression analyses were performed to identify factors independently associated with RFS and OS.ResultsAll patients successfully underwent LT following DEB-TACE with a mean interval of 2.3 months. The objective response rates (ORRs) for these patients following DEB-TACE was 82.5%. The primary AE was post-embolization syndrome (PES), with affected patients experiencing grades I and II. The median RFS and OS were 12.0 months (95%CI: 0.0-30.1) and 52.0 months (95%CI: 11.8–92.2) over the follow-up period until December 2022. The 2-year RFS and OS rates were 42.5%, and 67.5%. Multivariate analyses revealed Child-Pugh classification (HR = 6.24; 95%CI,1.83–21.24; P = 0.01) and macrovascular invasion (MAV) (HR = 3.89; 95%CI,1.07–14.15; P = 0.04) were both significant independent predictors of OS.ConclusionsDEB-TACE can serve as a safe and effective LRT in HCC patients beyond HC before LT, and can improve the prognosis of patients, especially without MAV. The higher Child–Pugh classification and MAV are independent prognostic factors after LT.

Regional Variation in Deescalated Therapy in Older Adults With Early-Stage Breast Cancer

Although trial data support the omission of axillary surgery and radiation therapy (RT) in women aged 70 years or older with T1N0 hormone receptor-positive (HR+) breast cancer, potential overtreatment in older adults with frailty persists. To determine how much geospatial variation in locoregional therapy may be attributed to region vs patient factors. This retrospective cross-sectional study included women aged 70 years or older who were diagnosed with HR+/ERBB2-negative (ERBB2-) breast cancer from January 1, 2013, to December 31, 2017. Data came from Surveillance, Epidemiology, and End Results-Medicare. Hierarchical multivariable modeling was used to evaluate the variance in deescalated care attributable to 4 domains, ie, (1) random, (2) region (health service area [HSA]), (3) patient factors, and (4) unexplained. Patient factors included age, frailty (validated claims-based measure), Charlson Comorbidity Index (CCI), and socioeconomic status (Yost index). Analyses were performed from January to October 2023. HSA. Deescalated care, defined as omission of axillary surgery, RT, or both. Standard therapy was defined as lumpectomy, axillary surgery, and RT or mastectomy with axillary surgery. Multivariable logistic regression was used to identify factors associated with deescalated care receipt. Of 9173 patients (mean [SD] age, 76.5 [5.2] years), 2363 (25.8%) were aged 80 years or older, 705 (7.7%) had frailty, and 419 (4.6%) had a CCI of 2 or greater. While 4499 (49.1%) underwent standard therapy, 4674 (50.9%) underwent deescalated therapy (1193 [13.0%] of the population omitted axillary surgery and 4342 [55.5%] of patients undergoing lumpectomy omitted RT). Of the total variance, random variation explained 27.3%, region/HSA explained 35.3%, patient factors explained 2.8%, and 34.5% was unexplained. In adjusted models, frailty and increased age were associated with a higher likelihood of undergoing deescalated therapy (frailty: odds ratio [OR], 1.70; 95% CI, 1.43-2.02; age, by 1-year increment: OR, 1.10; 95% CI, 1.09-1.11), but CCI was not. Patients in rural areas compared with those in urban areas (OR, 0.82; 95% CI, 0.68-0.99) and Asian and Pacific Islander patients compared with non-Hispanic White patients (OR, 0.68; 95% CI, 0.54-0.85) had a lower likelihood of undergoing deescalated therapy. In this retrospective cross-sectional study of women aged 70 years or older diagnosed with T1N0 HR+/ERBB2- breast cancer, region/HSA contributed more to the variation in deescalated therapy use than patient factors. Unexplained variation may be attributed to unmeasured characteristics, such as multidisciplinary environment and patient preference. Decision support efforts to address overtreatment should target regions with low rates of evidence-based deescalation.