Radioembolization Research Articles

Impact of Pharmaceutical Prophylaxis on Radiation-Induced Liver Disease Following Radioembolization.

Simple SummaryRadioembolization has failed to prove survival benefit in randomized trials, and, depending on various factors including tumor biology, response rates may vary considerably. Studies showed positive correlations between survival and absorbed tumor dose. Therefore, increasing currently prescribed tumor doses may be favorable for improving patient outcomes. The dominant limiting factor for increasing RE dose prescriptions is the relatively low tolerance of liver parenchyma to radiation with the possible consequence of a radiation-induced liver disease. Advances in RILD prevention may help increasing tolerable radiation doses to improve patient outcomes. Our study aimed to evaluate the impact of post-therapeutic RILD-prophylaxis in a cohort of intensely pretreated liver metastatic breast cancer patients. The results of this study as well as pathophysiological considerations warrant further investigations of RILD prophylaxis to increase dose prescriptions in radioembolization.Background: Radioembolization (RE) with yttrium-90 (90Y) resin microspheres yields heterogeneous response rates in with primary or secondary liver cancer. Radiation-induced liver disease (RILD) is a potentially life-threatening complication with higher prevalence in cirrhotics or patients exposed to previous chemotherapies. Advances in RILD prevention may help increasing tolerable radiation doses to improve patient outcomes. This study aimed to evaluate the impact of post-therapeutic RILD-prophylaxis in a cohort of intensely pretreated liver metastatic breast cancer patients; Methods: Ninety-three patients with liver metastases of breast cancer received RE between 2007 and 2016. All Patients received RILD prophylaxis for 8 weeks post-RE. From January 2014, RILD prophylaxis was changed from ursodeoxycholic acid (UDCA) and prednisolone (standard prophylaxis [SP]; n = 59) to pentoxifylline (PTX), UDCA and low-dose low molecular weight heparin (LMWH) (modified prophylaxis (MP); n = 34). The primary endpoint was toxicity including symptoms of RILD; Results: Dose exposure of normal liver parenchyma was higher in the modified vs. standard prophylaxis group (47.2 Gy (17.8–86.8) vs. 40.2 Gy (12.5–83.5), p = 0.017). All grade RILD events (mild: bilirubin ≥ 21 µmol/L (but <30 μmol/L); severe: (bilirubin ≥ 30 µmol/L and ascites)) were observed more frequently in the SP group than in the MP group, albeit without significance (7/59 vs. 1/34; p = 0.140). Severe RILD occurred in the SP group only (n = 2; p > 0.1). ALBI grade increased in 16.7% patients in the MP and in 27.1% patients in the SP group, respectively (group difference not significant); Conclusions: At established dose levels, mild or severe RILD events proved rare in our cohort. RILD prophylaxis with PTX, UDCA and LMWH appears to have an independent positive impact on OS in patients with metastatic breast cancer and may reduce the frequency and severity of RILD. Results of this study as well as pathophysiological considerations warrant further investigations of RILD prophylaxis presumably targeting combinations of anticoagulation (MP) and antiinflammation (SP) to increase dose prescriptions in radioembolization.

CFD Simulations of Radioembolization: A Proof-of-Concept Study on the Impact of the Hepatic Artery Tree Truncation

Radioembolization (RE) is a treatment for patients with liver cancer, one of the leading cause of cancer-related deaths worldwide. RE consists of the transcatheter intraarterial infusion of radioactive microspheres, which are injected at the hepatic artery level and are transported in the bloodstream, aiming to target tumors and spare healthy liver parenchyma. In paving the way towards a computer platform that allows for a treatment planning based on computational fluid dynamics (CFD) simulations, the current simulation (model preprocess, model solving, model postprocess) times (of the order of days) make the CFD-based assessment non-viable. One of the approaches to reduce the simulation time includes the reduction in size of the simulated truncated hepatic artery. In this study, we analyze for three patient-specific hepatic arteries the impact of reducing the geometry of the hepatic artery on the simulation time. Results show that geometries can be efficiently shortened without impacting greatly on the microsphere distribution.

Yttrium-90 Radioembolization to the Prostate Gland: Proof of Concept in a Canine Model and Clinical Translation

PurposeTo investigate the feasibility, safety, and absorbed-dose distribution of prostatic artery radioembolization (RE) in a canine model. Materials and MethodsFourteen male castrated beagles received dihydroandrosterone/estradiol to induce prostatic hyperplasia for the duration of the study. Each dog underwent fluoroscopic prostatic artery catheterization. Yttrium-90 (90Y) microspheres (TheraSphere; Boston Scientific, Marlborough, Massachusetts) were delivered to 1 prostatic hemigland (dose escalation from 60 to 200 Gy), with the contralateral side serving as a control. Assessments for adverse events were performed throughout the follow-up (Common Terminology Criteria for Adverse Events v5.0). Positron emission tomography/magnetic resonance (MR) imaging provided a confirmation after the delivery of absorbed-dose distribution. MR imaging was performed before and 3, 20, and 40 days after RE. Tissue harvest of the prostate, rectum, bladder, urethra, penis, and neurovascular bundles was performed 60 days after RE. ResultsAll the animals successfully underwent RE. Positron emission tomography/MR imaging demonstrated localization to and good coverage of only the treated hemigland. No adverse events occurred. The MR imaging showed a significant dose-dependent decrease in the treated hemigland size at 40 days (25%–60%, P < .001). No extraprostatic radiographic changes were observed. Necropsy demonstrated no gross rectal, urethral, penile, or bladder changes. Histology revealed RE-induced changes in the treated prostatic tissues of the highest dose group, with gland atrophy and focal necrosis. No extraprostatic RE-related histologic findings were observed. ConclusionsProstate 90Y RE is safe and feasible in a canine model and leads to focal dose-dependent changes in the gland without inducing unwanted extraprostatic effects. These results suggest that an investigation of nonoperative prostate cancer is warranted.

An estimate of 90Y dosimetry for bremsstrahlung SPECT/CT imaging in liver therapy with 90Y microspheres

ObjectiveBremsstrahlung SPECT/CT (bSPECT/CT) is one of the most common methods for post-therapy imaging in 90Y microspheres selective internal radiation therapy (SIRT) of liver cancers. Here, we are proposing a simple approach using bSPECT/CT to estimate mean absorbed dose to the liver in patients undergoing treatment with 90Y microspheres. Materials and methodsIn our previous study comparing 90Y dosimetry obtained using bSPECT/CT vs PET/CT, we found that there was a large difference between the mean absorbed dose values to the whole-liver. However, there was a high linear correlation between the doses, which presented an opportunity for quantitative assessment using bSPECT/CT 90Y imaging. In this study, after treatment with 90Y microspheres, 43 patients were immediately imaged on a dual-head Infinia SPECT/CT gamma camera and on a mCT PET/CT system. Images from 25 of the patients, randomly selected, were used to calculate the correlation of mean liver doses obtained from bSPECT/CT vs. PET/CT. For the remaining 18 patients, the calculated correlation was used to estimate doses obtained from bSPECT/CT, and these estimations were then compared to the doses obtained from PET/CT, considered the gold standard for quantitative analysis. ResultsFrom the 25 selected patients, the calculated linear correlation between bSPECT/CT and PET/CT 90Y mean absorbed doses in whole liver was high (r^2 = 0.97), with a slope of 2.80 and an intercept of -0.63. This linear fit was used to calculate the bSPECT/CT doses for the remaining 18 patients. For these patients, the mean whole-liver dose obtained from bSPECT/CT fitted data vs that obtained from PET/CT were 50.59 Gy and 50.81 Gy, respectively. The average dose difference was 0.2 ± 5.4 Gy (range −18.2%–13.0%). The repeatability coefficient was 10.5 (20.8 % of the mean). ConclusionAlthough quantitative bremsstrahlung imaging is difficult, it is possible to calculate adequate estimates of whole-liver dosimetry from bSPECT/CT imaging that is calibrated using its correlation with post-therapy PET/CT 90Y images.

ACR–ABS–ACNM–ASTRO–SIR–SNMMI practice parameter for selective internal radiation therapy or radioembolization for treatment of liver malignancies

PurposeThe American College of Radiology (ACR), American Brachytherapy Society (ABS), American College of Nuclear Medicine (ACNM), American Society for Radiation Oncology (ASTRO), Society of Interventional Radiology (SIR), and Society of Nuclear Medicine and Molecular Imaging (SNMMI) have jointly developed a practice parameter on selective internal radiation therapy (SIRT) or radioembolization for treatment of liver malignancies. Radioembolization is the embolization of the hepatic arterial supply of hepatic primary tumors or metastases with a microsphere yttrium-90 brachytherapy device. Materials and MethodsThe ACR -ABS -ACNM -ASTRO -SIR -SNMMI practice parameter for SIRT or radioembolization for treatment of liver malignancies was revised in accordance with the process described on the ACR website (https://www.acr.org/ClinicalResources/Practice-Parameters-and-Technical-Standards) by the Committee on Practice Parameters—Interventional and Cardiovascular Radiology of the ACR Commission on Interventional and Cardiovascular, Committee on Practice Parameters and Technical Standards—Nuclear Medicine and Molecular Imaging of the ACR Commission on Nuclear Medicine and Molecular Imaging and the Committee on Practice Parameters—Radiation Oncology of the ACR Commission on Radiation Oncology in collaboration with ABS, ACNM, ASTRO, SIR, and SNMMI. ResultsThis practice parameter is developed to serve as a tool in the appropriate application of radioembolization in the care of patients with conditions where indicated. It addresses clinical implementation of radioembolization including personnel qualifications, quality assurance standards, indications, and suggested documentation. ConclusionsThis practice parameter is a tool to guide clinical use of radioembolization. It focuses on the best practices and principles to consider when using radioemboliozation effectively. The clinical benefit and medical necessity of the treatment should be tailored to each individual patient.

Liver-Directed Therapies for Neuroendocrine Neoplasms.

To comprehensively synthesise and appraise the available evidence regarding therapies for metastatic neuroendocrine neoplasms that exploit the hepatic vasculature to deliver therapy to liver metastases. Various techniques including transarterial embolisation/chemoembolisation (TAE/TACE) and selective internal radiotherapy (SIRT, also termed radioembolisation [RE]) have been examined in patents with neuroendocrine liver metastases. Variations in the radioactive agents for selective internal radiotherapy (SIRT) have been explored, such as the use of Holmium-166, in addition to more established agents such as Yttrium-90. Recent trials have examined the safety and efficacy of combining liver-targeted therapy with systemic treatments, such as peptide receptor radionuclide therapy. More retrospective case series of liver-directed modalities will not provide additional knowledge. Randomised clinical trials have begun to compare the efficacy of different forms of liver-directed therapies, and also their combination with systemic treatment. Their results are expected to guide optimal treatment sequencing within multimodal concepts.

Impact of contouring methods on pre-treatment and post-treatment dosimetry for the prediction of tumor control and survival in HCC patients treated with selective internal radiation therapy

IntroductionThe aim of this study was to evaluate the impact of the contouring methods on dose metrics and their predictive value on tumor control and survival, in both situations of pre-treatment and post-treatment dosimetry, for patients with advanced HCC treated with SIRT.MethodsForty-eight patients who underwent SIRT between 2012 and 2020 were retrospectively included in this study. Target volumes were delineated using two methods: MRI-based contours manually drawn by a radiologist and then registered on SPECT/CT and PET/CT via deformable registration (Pre-CMRI and Post-CMRI), 99mTc-MAA-SPECT and 90Y-microspheres-PET 10% threshold contouring (Pre-CSPECT and Post-CPET). The mean absorbed dose (Dm) and the minimal absorbed dose delivered to 70% of the tumor volume (D70) were evaluated with both contouring methods; the tumor-to-normal liver uptake ratio (TNR) was evaluated with MRI-based contours only. Tumor response was assessed using the mRECIST criteria on the follow-up MRIs.ResultsNo significant differences were found for Dm and TNR between pre- and post-treatment. TNR evaluated with radiologic contours (Pre-CMRI and Post-CMRI) were predictive of tumor control at 6 months on pre- and post-treatment dosimetry (OR 5.9 and 7.1, respectively; p = 0.02 and 0.01). All dose metrics determined with both methods were predictive of overall survival (OS) on pre-treatment dosimetry, but only Dm with MRI-based contours was predictive of OS on post-treatment images with a median of 23 months for patients with a supramedian Dm versus 14 months for the others (p = 0.04).ConclusionIn advanced HCC treated with SIRT, Dm and TNR determined with radiologic contours were predictive of tumor control and OS. This study shows that a rigorous clinical workflow (radiologic contours + registration on scintigraphic images) is feasible and should be prospectively considered for improving therapeutic strategy.

3D voxel-based dosimetry to predict contralateral hypertrophy and an adequate future liver remnant after lobar radioembolization

Volume changes induced by selective internal radiation therapy (SIRT) may increase the possibility of tumor resection in patients with insufficient future liver remnant (FLR). The aim was to identify dosimetric and clinical parameters associated with contralateral hepatic hypertrophy after lobar/extended lobar SIRT with 90Y-resin microspheres. Patients underwent 90Y PET/CT after lobar or extended lobar (right + segment IV) SIRT. 90Y voxel dosimetry was retrospectively performed (PLANET Dose; DOSIsoft SA). Mean absorbed doses to tumoral/non-tumoral-treated volumes (NTL) and dose-volume histograms were extracted. Clinical variables were collected. Patients were stratified by FLR at baseline (T0-FLR): < 30% (would require hypertrophy) and ≥ 30%. Changes in volume of the treated, non-treated liver, and FLR were calculated at < 2 (T1), 2-5 (T2), and 6-12months (T3) post-SIRT. Univariable and multivariable regression analyses were performed to identify predictors of atrophy, hypertrophy, and increase in FLR. The best cut-off value to predict an increase of FLR to ≥ 40% was defined using ROC analysis. Fifty-six patients were studied; most had primary liver tumors (71.4%), 40.4% had cirrhosis, and 39.3% had been previously treated with chemotherapy. FLR in patients with T0-FLR < 30% increased progressively (T0: 25.2%; T1: 32.7%; T2: 38.1%; T3: 44.7%). No dosimetric parameter predicted atrophy. Both NTL-Dmean and NTL-V30 (fraction of NTL exposed to ≥ 30Gy) were predictive of increase in FLR in patients with T0 FLR < 30%, the latter also in the total cohort of patients. Hypertrophy was not significantly associated with tumor dose or tumor size. When ≥ 49% of NTL received ≥ 30Gy, FLR increased to ≥ 40% (accuracy: 76.4% in all patients and 80.95% in T0-FLR < 30% patients). NTL-Dmean and NTL exposed to ≥ 30Gy (NTL-V30) were most significantly associated with increase in FLR (particularly among patients with T0-FLR < 30%). When half of NTL received ≥ 30Gy, FLR increased to ≥ 40%, with higher accuracy among patients with T0-FLR < 30%.

Impact of staging on survival outcomes: a nationwide real-world cohort study of metastatic uveal melanoma.

No data exist regarding whether any first-line treatment for metastatic uveal melanoma provides overall survival (OS) benefit, if staged and compared to best supportive care (BSC). We analyzed OS in a nationwide, consecutive cohort diagnosed with metastatic uveal melanoma between January 1999 and December 2016. The Helsinki University Hospital Working Formulation was used to assign patients to stage IVa, IVb and IVc, corresponding to predicted median OS ≥12, <12-6 and <6 months, respectively. OS of 216 actively treated patients was compared by treatment and working formulation stage against 108 similarly staged, concurrent patients managed with BSC using Kaplan-Meier analysis and Cox regression. The median OS with active treatment was 18 (range, 0.7-162), 6.9 (range, 1.3-30) and 1.9 (range, 0.2-18) months in working formulation stage IVa, IVb and IVc, respectively. Patients who received chemoimmunotherapy, selective internal radiation therapy, or underwent surgical resection survived longer - median OS 13, 16 and 24 months, respectively - than those receiving conventional chemotherapy - median OS 5.1 months - but only with surgical resection their OS exceeded that with BSC, both overall and in stage IVa (P < 0.001, P = 0.010). In stage IVb and IVc, no difference in OS was observed in any comparison. Staging of patients is crucial when comparing survival after metastatic uveal melanoma. Only surgical resection for stage IVa disease provided longer OS in our national cohort. We additionally recommend stage-specific comparison of novel treatments against available BSC data.

The joint use of 99mTc-MAA-SPECT/CT and cone-beam CT optimizes radioembolization planning

PurposeTo determine which imaging method used during radioembolization (RE) work-up: contrast-enhanced computed tomography (CECT), 99mTc-MAA-SPECT/CT or cone beam-CT (CBCT), more accurately predicts the final target volume (TgV) as well as the influence that each modality has in the dosimetric calculation.MethodsTgVs from 99mTc-MAA-SPECT/CT, CECT and CBCT were consecutively obtained in 24 patients treated with RE and compared with 90Y PET/CT TgV. Using the TgVs estimated by each imaging modality and a fictitious activity of 1 GBq, the corresponding absorbed doses by tumor and non-tumoral parenchyma were calculated for each patient. The absorbed doses for each modality were compared with the ones obtained using 90Y PET/CT TgV.Results99mTc-MAA-SPECT/CT predicted 90Y PET/CT TgV better than CBCT or CECT, even for selective or superselective administrations. Likewise, 99mTc-MAA-SPECT/CT showed dosimetric values more similar to those obtained with 90Y PET/CT. Nevertheless, CBCT provided essential information for RE planning, such as ensuring the total coverage of the tumor and, in cases with more than one feeding artery, splitting the activity according to the volume of tumor perfused by each artery.ConclusionThe joint use of 99mTc-MAA-SPECT/CT and CBCT optimizes dosimetric planning for RE procedures, enabling a more accurate personalized approach.

NICE approval of selective internal radiation therapy for advanced HCC

NICE approval of selective internal radiation therapy for advanced HCC

Intra- inter-observer repeatability in liver computed tomography volumetry in patients undergoing radioembolization simulation.

The careful evaluation of MDCT is an essential step for the treatment planning in pre-treatment imaging work-up for Trans-Arterial Radio Embolization (TARE). It may provide unique volumetric data (CTVs), which are information useful for an effective and safe TARE. The purpose of this study is to demonstrate that the radiographer is able to calculate CTVs of TARE simulation with the same precision as the interventional radiologist. This study retrospectively considers 17 consecutive patients (8 males, 9 females; mean age 66.3 ± 13.2years) who underwent pre-treatment work-up for TARE, between May 2019 and February 2020 (trial ID:2234 - protocol). For each patient, four specific parameters are evaluated from MDCT achieved during treatment simulation: healthy liver volume (HLV), the whole hepatic parenchyma (THV = healthy liver and TTV = tumour) involved by TARE, and whole liver volume (WLV). Four independent observers-R1 (expert interventional radiologist), T1, T2, and T3 (radiographers, with different experiences in the field of interventional radiology)-are involved in the imaging analysed. All the 4 observers detected the same number of hepatic lesion(s) per patient. Regarding the three radiographers, the intra-observer reliability for CTVs is very high 0.997 to 1.000 (95%CI). Also inter-observer reproducibility between radiographers is excellent regarding CTVs, 0.965 to 0.999 (95%CI). The accuracy of radiographer evaluation is very high 0.964 to 0.999 (95%CI). The high intra- and inter-observer reproducibility shows that a properly trained radiographers might have the same accuracy as interventional radiologists, in assessing liver CTV data for planning TARE.

Yttrium-90 radioembolization of isolated hepatic adrenocortical carcinoma metastases with negative surgical pathology

BackgroundAdrenocortical carcinoma (ACC) is an uncommon malignancy with an estimated 15,400 new cases annually across the globe. The prognosis is generally poor as the disease is often already advanced at initial diagnosis due to non-specific symptoms. Even for local disease, recurrence after surgical resection is high. Treatment choices for advanced disease include mitotane, chemotherapy, ablation, chemoembolization, radioembolization, and external beam radiotherapy, with varying degrees of efficacy. To the best of our knowledge, there have only been two prior case studies of complete clinical and radiological response of stage 4 disease at 1 year and 2 years after yttrium-90 (90Y) microsphere selective internal radiation therapy (SIRT) of isolated hepatic metastases post-surgery and chemotherapy.Case presentationWe present a case of a 58-year-old man with metastatic ACC who was treated with 90Y resin microsphere (SIR-spheres) for local control of liver metastases leading to a surgically proven negative pathology after partial hepatectomy 7 months after SIRT. The patient was initially diagnosed with stage 1 ACC that progressed 6 years later to stage 4 disease with new liver metastases that were deemed unresectable at an outside institution. After review of the case at multidisciplinary tumor board, he was referred for liver directed therapy for local tumor control. Angiographic workup demonstrated partial extrahepatic supply to the tumors from the right inferior phrenic artery, which was successfully embolized on the day of SIRT for flow redistribution. As the patient was being treated with mitotane that suppresses steroid production, he developed post-SIRT adrenal crisis, which was successfully controlled with steroids, highlighting the need for pre SIRT stress dose steroids.ConclusionsThis case continues to add to the literature supporting 90Y radioembolization as an effective treatment for isolated hepatic ACC metastases. Our case is the first to demonstrate surgically proven negative pathology after radioembolization. Further prospective study is warranted to better establish efficacy as well as safety of SIRT for ACC liver metastases.

A proof-of-concept study of the in-vivo validation of a computational fluid dynamics model of personalized radioembolization

Radioembolization (RE) with yttrium-90 (90Y) microspheres, a transcatheter intraarterial therapy for patients with liver cancer, can be modeled computationally. The purpose of this work was to correlate the results obtained with this methodology using in vivo data, so that this computational tool could be used for the optimization of the RE procedure. The hepatic artery three-dimensional (3D) hemodynamics and microsphere distribution during RE were modeled for six 90Y-loaded microsphere infusions in three patients with hepatocellular carcinoma using a commercially available computational fluid dynamics (CFD) software package. The model was built based on in vivo data acquired during the pretreatment stage. The results of the simulations were compared with the in vivo distribution assessed by 90Y PET/CT. Specifically, the microsphere distribution predicted was compared with the actual 90Y activity per liver segment with a commercially available 3D-voxel dosimetry software (PLANET Dose, DOSIsoft). The average difference between the CFD-based and the PET/CT-based activity distribution was 2.36 percentage points for Patient 1, 3.51 percentage points for Patient 2 and 2.02 percentage points for Patient 3. These results suggest that CFD simulations may help to predict 90Y-microsphere distribution after RE and could be used to optimize the RE procedure on a patient-specific basis.

Changing trends in hepatocellular carcinoma management: Results from a nationwide database in the last decade

ObjectiveThe therapeutic strategies for hepatocellular carcinoma (HCC) have greatly expanded in recent years. However, the actual usage of each of these treatments in clinical routine remains unknown. Here, we analysed the distribution and changes of the main surgical and radiological therapeutic procedures nationwide during the last decade. MethodsRetrospectively, analysis of the data on all >18-year-old patients with a diagnosis of HCC identified in the French Program for the Medicalization of Information Systems database that contains all discharge summaries from all French hospitals. The number and percentage of the therapeutic procedures performed from January 2010 to December 2019 were extracted. ResultsA total of 68,416 therapeutic procedures were performed in 34,000 HCC patients. Whereas HCC incidence remained stable, the annual number of procedures frankly increased over the decade (from 4267 to 8042). Trans-arterial chemoembolization was the most frequently performed technical procedure, with a double-digit annual growth from 2010 (n = 1932) to 2015 (n = 4085), before stabilization from 2016. Selective internal radiation therapy displayed the highest increase in the decade (+475%). Among curative treatments, the annual number of percutaneous tumour ablations more than doubled in 10 years, till representing 64% of curative treatments in cirrhotic patients in 2019. Surgical tumour resections showed a 1.5-fold increase in 10 years, due to the great increase in minimally invasive approaches, whereas the proportion of open resection progressively decreased. ConclusionMinimally invasive procedures have gained major importance in HCC management during the last decade. Percutaneous thermal ablation has emerged as the first curative treatment performed for patients with HCC.

A systematic literature review and network meta-analysis of first-line treatments for unresectable hepatocellular carcinoma based on data from randomized controlled trials

ABSTRACT Background Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer. First-line treatment options for unresectable HCC include sorafenib, lenvatinib, selective internal radiation therapy (SIRT), and transarterial chemoembolization (TACE). The present study reviewed randomized controlled trials (RCTs) of first-line therapies for unresectable HCC in TACE-ineligible patients. Research design and methods A systematic literature review (SLR) was conducted to identify RCTs of first-line treatments for TACE-ineligible patients with unresectable HCC. Data on overall survival (OS) and progression-free survival were extracted and a contrast-based Bayesian network meta-analysis (NMA) was conducted using Markov Chain Monte Carlo techniques. Results The SLR identified three RCTs: two comparing Y-90 resin microspheres with sorafenib, and one comparing sorafenib with lenvatinib. No RCTs were identified comparing other SIRT technologies with any other approved first-line HCC therapies. The NMA showed no significant OS differences between Y-90 resin microspheres and sorafenib (hazard ratio [HR] 0.92, 95% credible interval [CrI]: 0.79–1.08) or lenvatinib (HR: 0.88, 95% CrI: 0.63–1.22). Conclusions An SLR and NMA showed no significant differences between sorafenib, lenvatinib, and Y-90 resin microspheres in treating unresectable HCC. RCT evidence was not available for any other SIRT technologies and an evaluation of their relative efficacy was therefore not possible.

Selective internal radiation therapy in the management of primary and metastatic disease in the liver.

Selective internal radiation therapy is a type of brachytherapy used to provide targeted radiotherapy, most commonly to treat primary or metastatic disease within the liver. This review outlines current clinical practice, dosimetric considerations, the pre-treatment workup and safety considerations before treatment. It also examines the clinical evidence for its use in patients with both primary and metastatic disease within the liver.

Hepatocellular carcinoma in non-alcoholic fatty liver disease-a review of an emerging challenge facing clinicians.

Non-alcoholic fatty liver disease (NAFLD) is a rapidly growing cause of chronic liver disease and is becoming a leading cause of hepatocellular carcinoma (HCC) in many developed countries. This presents major challenges for the surveillance, diagnosis and treatment of HCC. To discuss the clinical challenges faced by clinicians in managing the rising number of NAFLD-HCC cases. MEDLINE, PubMed and Embase databases were searched using the keywords; NAFLD, HCC, surveillance, hepatectomy, liver transplantation, percutaneous ablation, transarterial chemoembolization (TACE), selective internal radiotherapy treatment (SIRT) and sorafenib. Relevant clinical studies were included. Current HCC surveillance programmes are inadequate because they only screen for HCC in patients with cirrhosis, whereas in NAFLD a significant proportion of HCC develops in the absence of cirrhosis. Consequently NAFLD patients often present with a more advanced stage of HCC, with a poorer prognosis. NAFLD-HCC patients also tend to be older and to have more co-morbidities compared to HCC of other etiologies. This limits the use of curative treatments such as liver resection and orthotopic liver transplantation (OLT). Evidence suggests that although NAFLD-HCC patients who undergo liver resection or OLT have worse perioperative and short-term outcomes, overall long-term survival is comparable to HCC of other etiologies. This highlights the importance of careful patient selection, pre-habilitation and perioperative planning for NAFLD-HCC patients being considered for surgical treatment. Careful consideration is also important for non-surgical treatments, although the evidence supporting treatment selection is frequently lacking, as these patients tend to be poorly represented in clinical trials. Locoregional therapies such as percutaneous ablation and TACE may be less well tolerated and less effective in NAFLD patients with obesity or diabetes. The tyrosine kinase inhibitor sorafenib may also be less effective. This review highlights how international guidelines, for which NAFLD traditionally has made up a small part of the evidence base, may not be appropriate for all NAFLD-HCC patients. Future guidelines need to reflect the changing landscape of HCC, by making specific recommendations for the management of NAFLD-HCC.

Early effect of 90Y radioembolisation on hepatocellular carcinoma and liver parenchyma stiffness measured with MR elastography: initial experience.

To quantify hepatocellular carcinoma (HCC) and liver parenchyma stiffness using MR elastography (MRE) and serum alpha fetoprotein (AFP), before and 6 weeks (6w) after 90Y radioembolisation (RE), and to assess the value of baseline tumour and liver stiffness (TS/LS) and AFP in predicting response at 6w and 6 months (6 m). Twenty-three patients (M/F 18/5, mean age 68.3 ± 9.3 years) scheduled to undergo RE were recruited into this prospective single-centre study. Patients underwent an MRI exam at baseline and 6w following RE (range 39-47 days) which included MRE using aprototype 2D EPI sequence. TS, peritumoural LS/LS remote from the tumour, tumour size, and AFP were measured at baseline and at 6w. Treatment response was determined using mRECIST at 6w and 6 m. MRE was technically successful in 17 tumours which were classified at 6w as complete response (CR, n = 7), partial response (PR, n = 4), and stable disease (SD, n = 6). TS and peritumoural LS were significantly increased following RE (p = 0.016, p = 0.039, respectively), while LS remote from tumour was unchanged (p = 0.245). Baseline TS was significantly lower in patients who achieved CR at 6w (p = 0.014). Baseline TS, peritumoural LS (both AUC = 0.857), and AFP (AUC = 0.798) showed fair/excellent diagnostic performance in predicting CR at 6w, but were not significant predictors of OR or CR at 6 m. Our initial results suggest that HCC TS and peritumoural LS increase early after RE. Baseline TS, peritumoural LS, and AFP were all significant predictors of CR to RE at 6w. These results should be confirmed in a larger study. • Magnetic resonance elastography-derived tumour stiffness and peritumoural liver stiffness increase significantly at 6 weeks post radioembolisation whereas liver stiffness remote from the tumour is unchanged. • Baseline tumour stiffness and peritumoural liver stiffness are lower in patients who achieve complete response at 6 weeks post radioembolisation. • Baseline tumour size is significantly correlated with baseline tumour stiffness.

Thermal Ablation, Embolization, and Selective Internal Radiation Therapy Combined with Checkpoint Inhibitor Cancer Immunotherapy: Safety Analysis

PurposeTo describe interventional oncology therapies combined with immune checkpoint inhibitor (ICI) therapy targeting the programmed death 1 pathway in patients with different neoplasms. Materials and MethodsThis was a retrospective cohort study of patients who underwent tumor-directed thermal ablation, embolization, or selective internal radiation therapy (SIRT) between January 1, 2011, and May 1, 2019, and received anti–programmed death 1/PD-L1 agents ≤ 90 days before or ≤ 30 days after the interventional procedure. Immune-related adverse events (irAEs) and procedural complications ≤ 90 days after the procedure were graded according to the Common Terminology Criteria for Adverse Events version 5.0. The study included 65 eligible patients (49% female; age 63 years ± 11.1). The most common tumors were metastatic melanoma (n = 28) and non–small cell lung cancer (NSCLC) (n = 12). Patients underwent 78 procedures (12 patients underwent > 1 procedure), most frequently SIRT (35.9%) and cryoablation (28.2%). The most common target organs were liver (46.2%), bone (24.4%), and lung (9.0%). Most patients received ICI monotherapy with pembrolizumab (n = 30), nivolumab (n = 22), and atezolizumab (n = 6); 7 patients received ipilimumab and nivolumab. ResultsSeven (10.8%) patients experienced an irAE (71.4% grade 1–2), mostly affecting the skin. Median time to irAE was 33 days (interquartile range, 19–38 days). Five irAEs occurred in patients with melanoma, and no irAEs occurred in patients with NSCLC. Management required corticosteroids (n = 3) and immunotherapy discontinuation (n = 1); all irAEs resolved to grade ≤ 1. There were 4 intraprocedural and 32 postprocedural complications (77.8% grade < 3). No grade 5 irAEs and/or procedural complications occurred. ConclusionsNo unmanageable or unanticipated toxicities occurred within 90 days after interventional oncology therapies combined with ICIs.