Application and research progress of selective internal radiation therapy with 90 Y microspheres in hepatocellular carcinoma

Applications in radiation therapy of a scintillating screen viewed by a CCD camera

Powerful radiotherapy for hepatocellular carcinoma.

Consensus Guidelines for Delineation of Clinical Target Volume for Intensity-Modulated Pelvic Radiation Therapy in Postoperative Treatment of Endometrial and Cervical Cancer- An Update

Streamlining TARE or personalizing SIRT? Different philosophies to treat different HCCs with Yttrium-90…

Clinical surface imaging systems designed for surface-guided radiation therapy (SGRT) applications are expensive and standard configurations have a limited capacity for raw data export which can prohibit innovation, new uses, and new techniques for surface-guided applications. Fortunately, the recent emergence of low-cost consumer-grade depth cameras has enabled a new frontier of imagination and exploration of the use of surfaces in radiation therapy applications. Over the last decade, much clinical and research work has investigated the use of both laser scanning systems and RGB-depth sensors including the Microsoft Kinect camera (Microsoft Corporation, Redmond, WA, USA). Consumer-grade depth cameras have been used for respiratory motion management, patient identification, collision detection and avoidance, 3D printing applications, patient alignment, and image processing. This chapter reviews methods and results of consumer-grade depth camera applications for radiation therapy over recent years spanning computer vision, motion management, full room scanning, and collision avoidance applications.

Hepatocellular Carcinoma Radiation Therapy: Review of Evidence and Future Opportunities

Focus

There is an increasing interest in the evaluation of lung function from physiological images in radiation therapy treatment planning to reduce the extent of postradiation toxicities. The purpose of this work was to retrieve reliable functional information from contrast-enhanced dual-energy computed tomography (DECT) for new applications in radiation therapy. The functional information obtained by DECT is also compared with other methods using single-energy CT (SECT) and single-photon emission computed tomography (SPECT) with CT. The differential function between left and right lung, as well as between lobes is computed for all methods. Five lung cancer patients were retrospectively selected for this study; each underwent a SPECT/CT scan and a contrast-injected DECT scan, using 100 and 140 Sn kVp. The DECT images are postprocessed into iodine concentration maps, which are further used to determine the perfused blood volume. These maps are calculated in two steps: (a) a DECT stoichiometric calibration adapted to the presence of iodine and followed by (b) a two-material decomposition technique. The functional information from SECT is assumed proportional to the HU numbers from a mixed CT image. The functional data from SPECT/CT are considered proportional to the number of counts. A radiation oncologist segmented the entire lung volume into five lobes on both mixed CT images and low-dose CT images from SPECT/CT to allow a regional comparison. The differential function for each subvolume is computed relative to the entire lung volume. The differential function per lobe derived from SPECT/CT correlates strongly with DECT (Pearson's coefficient r = 0.91) and moderately with SECT (r = 0.46). The differential function for the left lung shows a mean difference of 7% between SPECT/CT and DECT; and 17% between SPECT/CT and SECT. The presence of nonfunctional areas, such as localized emphysema or a lung tumor, is reflected by an intensity drop in the iodine concentration maps. Functional dose volume histograms (fDVH) are also generated for two patients as a proof of concept. The extraction of iodine concentration maps from a contrast-enhanced DECT scan is achieved to compute the differential function for each lung subvolume and good agreement is found in respect to SPECT/CT. One promising avenue in radiation therapy is to include such functional information during treatment planning dose optimization to spare functional lung tissues.

Quality Improvement Guidelines for Transhepatic Arterial Chemoembolization, Embolization, and Chemotherapeutic Infusion for Hepatic Malignancy

Toxicity and dosimetry in SORAMIC study

The emerging questionable benefit of sorafenib as a neo-adjuvant in HCC patients treated with Y-90 radioembolization pending liver transplantation

Hepatocellular carcinoma (HCC) management has evolved over the past two decades, with the development of newer treatment modalities. While various options are available, unmet needs are reflected through the mixed treatment outcome for intermediate-stage HCC. As HCC is radiosensitive, radiation therapies have a significant role in management. Radiation therapies offer local control for unresectable lesions and for patients who are not surgical candidates. Radiotherapy also provides palliation in metastatic disease, and acts as a bridge to resection and transplantation in selected patients. Advancements in radiotherapy modalities offer improved dose planning and targeted delivery, allowing for better tumor response and safer dose escalations while minimizing the risks of radiation-induced liver damage. Radiotherapy modalities are broadly classified into external beam radiation therapy and selective internal radiation therapy. With emerging modalities, radiotherapy plays a complementary role in the multidisciplinary care of HCC patients. We aim to provide an overview of the role and clinical application of radiation therapies in HCC management. The continuous evolution of radiotherapy techniques allows for improved therapeutic outcomes while mitigating unwanted adverse effects, making it an attractive modality in HCC management. Rigorous clinical studies, quality research and comprehensive datasets will further its application in the present era of evidence-based practice in Medicine.

We report a HBsAg-positive patient who developed hepatocellular carcinoma (HCC) 7 years after cadaveric kidney transplantation. The tumor was unresectable because of coexisting cirrhosis. Selective internal radiation (SIR) therapy, a novel therapy with the technique recently perfected, was used. Yttrium-90 microspheres were given via an angiographic catheter under fluoroscopy guidance. Serum alpha-fetal protein (AFP) was normalized within 2 wk. A follow-up abdominal CT scan revealed significant necrosis of the tumor and compensatory hypertrophy of non-diseased liver. The treatment was well tolerated except for transient liver function deterioration. The patient enjoyed 15 months of symptom-free survival before she died of liver failure. Practical aspects and potential applications of SIR therapy in this group of patients are discussed.

Hepatocellular carcinoma is the most common type of primary liver cancer. Treatment choice is dependent on underlying liver dysfunction and cancer stage. Treatment options include conventional transarterial therapies for patients with intermediate-stage disease and systemic therapy [e.g. sorafenib (Nexavar®; Bayer plc, Leverkusen, Germany)] for patients with advanced-stage disease. Selective internal radiation therapies deliver radiation to liver tumours via microspheres that are injected into the hepatic artery. There are three selective internal radiation therapies: TheraSphere™ [BTG Ltd, London, UK (now Boston Scientific, Marlborough, MA, USA)], SIR-Spheres® (Sirtex Medical Ltd, Woburn, MA, USA) and QuiremSpheres® (Quirem Medical BV, Deventer, the Netherlands). To assess the clinical effectiveness and cost-effectiveness of selective internal radiation therapies for treating patients with unresectable early-, intermediate- or advanced-stage hepatocellular carcinoma. A search was undertaken to identify clinical effectiveness literature relating to selective internal radiation therapies and relevant comparators for the treatment of hepatocellular carcinoma. Studies were critically appraised and summarised. The network of evidence was mapped to estimate the relative effectiveness of the different selective internal radiation therapies and comparator treatments. An economic analysis evaluated the cost-effectiveness. Twenty studies were included in the clinical effectiveness review. Two large randomised controlled trials rated as having a low risk of bias [SARAH: Vilgrain V, Pereira H, Assenat E, Guiu B, Ilonca AD, Pageaux GP, et al. Efficacy and safety of selective internal radiotherapy with yttrium-90 resin microspheres compared with sorafenib in locally advanced and inoperable hepatocellular carcinoma (SARAH): an open-label randomised controlled Phase 3 trial. Lancet Oncol 2017;18:1624-36; and SIRveNIB: Chow PKH, Gandhi M, Tan SB, Khin MW, Khasbazar A, Ong J, et al. SIRveNIB: selective internal radiation therapy versus sorafenib in Asia-Pacific patients with hepatocellular carcinoma. J Clin Oncol 2018;36:1913-21] found no significant difference in overall survival or progression-free survival between SIR-Spheres and sorafenib (systemic therapy) in an advanced population, despite greater tumour response in the SIR-Spheres arm of both trials. There were some concerns regarding generalisability of the SARAH and SIRveNIB trials to UK practice. All other studies of SIR-Spheres, TheraSphere or QuiremSpheres were either rated as being at a high risk of bias or caused some concerns regarding bias. A network meta-analysis was conducted in adults with unresectable hepatocellular carcinoma who had Child-Pugh class A liver cirrhosis and were ineligible for conventional transarterial therapies. The analysis included the SARAH and SIRveNIB trials as well as a trial comparing lenvatinib (Kisplyx®; Eisai Ltd, Tokyo, Japan) (systemic therapy) with sorafenib. There were no meaningful differences in overall survival between any of the treatments. The base-case economic analysis suggested that TheraSphere may be cost-saving relative to both SIR-Spheres and QuiremSpheres. However, incremental cost differences between TheraSphere and SIR-Spheres were small. In a fully incremental analysis, which included confidential Patient Access Scheme discounts, lenvatinib was the most cost-effective treatment and dominated all selective internal radiation therapies. In pairwise comparisons of sorafenib with each selective internal radiation therapy, sorafenib also dominated all selective internal radiation therapies. The existing evidence cannot provide decision-makers with clear guidance on the comparative effectiveness of treatments in early- and intermediate-stage hepatocellular carcinoma or on the efficacy of TheraSphere or QuiremSpheres. In the advanced-stage hepatocellular carcinoma population, two large randomised trials have shown that SIR-Spheres have similar clinical effectiveness to sorafenib. None of the selective internal radiation therapies was cost-effective, being more costly and less effective than lenvatinib, both at list price and with Patient Access Scheme discounts. Future studies may wish to include early- and intermediate-stage hepatocellular carcinoma patients and the low tumour burden/albumin-bilirubin 1 subgroup of advanced-stage patients. Future high-quality studies evaluating alternative selective internal radiation therapies would be beneficial. This study is registered as PROSPERO CRD42019128383. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 48. See the NIHR Journals Library website for further project information.

Simple SummaryHepatocellular carcinoma (HCC) is one of the deadliest forms of cancer. Selective internal radiation therapy (SIRT) is one of the therapeutic options for treatment of advanced HCC. Studies show that SIRT has a high objective response rate, but lack of survival benefit when compared to different treatment modalities. We hypothesized that this is due to potential damage in healthy liver parenchyma as a side-effect of SIRT, resulting in functional changes to the liver. This can ultimately result in liver decompensation and potentially death. The aim of this retrospective study was to assess long-term liver-related complications after SIRT in patients with HCC. We analyzed patients who underwent SIRT and found that liver decompensation occurred more often after SIRT when compared to sorafenib. However, careful patient selection may result in a survival benefit after SIRT when compared to other treatments. The ABLI score may be a valuable prognostic score for selecting patients.Selective internal radiation therapy (SIRT) is used as a treatment for hepatocellular carcinoma (HCC). The aim of this study was to assess long-term liver-related complications of SIRT in patients who had not developed radioembolization-induced liver disease (REILD). The primary outcome was the percentage of patients without REILD that developed Child-Pugh (CP) ≥ B7 liver decompensation after SIRT. The secondary outcomes were overall survival (OS) and tumor response. These data were compared with a matched cohort of patients treated with sorafenib. Eighty-five patients were included, of whom 16 developed REILD. Of the remaining 69 patients, 38 developed liver decompensation CP ≥ B7. The median OS was 18 months. In patients without REILD, the median OS in patients with CP ≥ B7 was significantly shorter compared to those without CP ≥ B7; 16 vs. 31 months. In the case-matched analysis, the median OS was significantly longer in SIRT-treated patients; 16 vs. 8 months in sorafenib. Liver decompensation CP ≥ B7 occurred significantly more in SIRT when compared to sorafenib; 62% vs. 27%. The ALBI score was an independent predictor of liver decompensation (OR 0.07) and OS (HR 2.83). After SIRT, liver decompensation CP ≥ B7 often developed as a late complication in HCC patients and was associated with a shorter OS. The ALBI score was predictive of CP ≥ B7 liver decompensation and the OS, and this may be a valuable marker for patient selection for SIRT.