Selective internal radiation therapy segmentectomy:A new minimally invasive curative option for primary liver malignancies?

Transarterial radioembolization or selective internal radiation therapy(SIRT)has emerged as a minimally invasive approach for the treatment of tumors.This percutaneous technique involves the local,intra-arterial delivery of radioactive microspheres directly into the tumor.Historically employed as a palliative measure for liver malignancies,SIRT has gained traction over the past decade as a potential curative option,mirroring the increasing role of radiation segmentectomy.The latest update of the BCLC hepatocellular carcinoma guidelines recognizes SIRT as an effective treatment modality comparable to other local ablative methods,particularly well-suited for patients where surgical resection or ablation is not feasible.Radiation segmentectomy is a more selective approach,aiming to deliver high-dose radiation to one to three specific hepatic segments,while minimizing damage to surrounding healthy tissue.Future research efforts in radiation segmentectomy should prioritize optimizing radiation dosimetry and refining the technique for super-selective administration of radiospheres within the designated hepatic segments.

Effects of Yttrium-90 selective internal radiation therapy on non-conventional liver tumors

The liver is a common site of metastasis, with essentially all metastatic malignancies having been known to spread to the liver. Nearly half of all patients with extrahepatic primary cancer have hepatic metastases. The severe prognostic implications of hepatic metastases have made surgical resection an important first line treatment in management. However, limitations such as the presence of extrahepatic spread or poor functional hepatic reserve exclude the majority of patients as surgical candidates, leaving chemotherapy and locoregional therapies as next best options. Selective internal radiation therapy(SIRT) is a form of catheter-based locoregional cancer treatment modality for unresectable tumors, involving trans-arterial injection of microspheres embedded with a radioisotope Yttrium-90. The therapeutic radiation dose is selectively delivered as the microspheres permanently embed themselves within the tumor vascular bed. Use of SIRT has been conventionally aimed at treating primary hepatic tumors(hepatocellular carcinoma) or colorectal and neuroendocrine metastases. Numerous reviews are available for these tumor types. However, little is known or reviewed on non-colorectal or nonneuroendocrine primaries. Therefore, the aim of this paper is to systematically review the current literature to evaluate the effects of Yttrium-90 radioembolization on non-conventional liver tumors including those secondary to breast cancer, cholangiocarcinoma, ocular and percutaneous melanoma, pancreatic cancer, renal cell carcinoma, and lung cancer.

Current status of yttrium-90 microspheres radioembolization in primary and metastatic liver cancer

Liver malignancy,including primary liver cancer and metastatic liver cancer has become one of the most common causes of cancer-related death worldwide due to the high malignant degree and limited systematic treatment strategy.Radioembolization with yttrium-90(^(90)Y)-loaded microspheres is a relatively novel technology that has made significant progress in the local treatment of liver malignancy.The different steps in the extensive work-up of radioembolization for patients with an indication for treatment with^(90)Y microspheres,from patient selection to follow up,both technically and clinically,are discussed in this paper.It describes the application and development of^(90)Y microspheres in the treatment of liver cancer.

An uncommon cause of gastro-duodenal ulceration

Gastrointestinal ulcers occur frequently and are mainly caused by H pylori infection. In this report, we present a rare case of gastro-duodenal ulcer following selective internal radiation therapy (SIRT). SIRT is a palliative treatment for unresectable liver tumours. During SIRT, 90Y-microspheres are infused into the hepatic artery. Pre- treatment evaluation for the presence of arterial shunts to neighbouring organs should be determined in order to avoid complications of SIRT.

Two-stage hepatectomy with radioembolization for bilateral colorectal liver metastases:A case report

BACKGROUND Two-stage hepatectomy(TSH)is a well-established surgical technique,used to treat bilateral colorectal liver metastases(CRLM)with a small future liver remnant(FLR).However,in classical TSH,drop-out is reported to be around 25%-40%,due to insufficient FLR increase or progression of disease.Trans-arterial radioembolization(TARE)has been described to control locally tumor growth of liver malignancies such as hepatocellular carcinoma,but it has been also reported to induce a certain degree of contralateral liver hypertrophy,even if at a lower rate compared to portal vein embolization or ligation.CASE SUMMARY Herein we report the case of a 75-year-old female patient,where TSH and TARE were combined to treat bilateral CRLM.According to computed tomography(CT)-scan,the patient had a hepatic lesion in segment VI-VII and two other confluent lesions in segment II-III.Therefore,one-stage posterior right sectionectomy plus left lateral sectionectomy(LLS)was planned.The liver volumetry estimated a FLR of 38%(segments I-IV-V-VIII).However,due to a more than initially planned,extended right resection,simultaneous LLS was not performed and the patient underwent selective TARE to segments II-III after the first surgery.The CT-scan performed after TARE showed a reduction of the treated lesion and a FLR increase of 55%.Carcinoembryonic antigen and CA 19.9 decreased significantly.Nearly three months later after the first surgery,LLS was performed and the patient was discharged without any postoperative complications.CONCLUSION According to this specific experience,TARE was used to induce liver hypertrophy and simultaneously control cancer progression in TSH settings for bilateral CRLM.

SIRT and Its Unresolved Problems—Is Imaging the Solution? A Review

Selective Internal Radiation Therapy (SIRT) is used as a treatment option for unresectable liver tumors. In SIRT, microspheres, which have a radioactive substance as an integral component, are placed via image guided catheters into the hepatic artery. The ionizing radiation is directly delivered to the tumor. Currently used commercially available microspheres are based on Yttrium 90, a β-emitter, which has been shown to be safe and to produce good clinical results. The technical features of Y90, their applications and their limitations are presented. Image guidance and intraoperative depiction of Yttrium 90 microspheres are restricted, which is currently one of the main limitations in SIRT. Therapy planning and control is currently based on pre- and post-operative images to evaluate the placement of the microspheres respectively. Holmium 166, another possible nuclide integrated into the microspheres emits a higher amount of secondary γ-radiation (Bremsstrahlung) than Yttrium 90. This enables an improved depiction of the microspheres inside the patient during and immediately after application, but comes with other shortfalls. Imaging of delivery and verification of the microsphere placement could solve many of the identified problems with SIRT. The different technologies are reviewed and an outlook in future developments is given particularly on image guidance and therapy control.

Large,multifocal or portal vein-invading hepatocellular carcinoma(HCC)downstaged by Y90 using personalized dosimetry:safety,pathological results and outcomes after surgery

Background:Transarterial radioembolization(TARE)has recently been recognized as a bridging/downstaging therapy to surgery for early hepatocellular carcinomas(HCCs)with high rates of complete pathological necrosis(CPN)on liver explants.In patients with portal vein tumoral thrombus(PVTT),multifocal or large tumors,TARE has mainly a palliative role and surgery remains controversial in this poor-prognosis population.Personalized dosimetry recently proved to outperform standard dosimetry used in prior negative Y90 randomized-controlled trials.Methods:In this retrospective study,we evaluated safety,radiological and pathological response and outcomes in HCC patients with PVTT,multifocal or large tumors,who underwent surgery after downstaging using TARE with Y90-loaded glass microspheres with personalized dosimetry.Results:Between December 2015 and October 2021,18 unresectable patients(14/18 with PVTT)had surgery(16 resections,2 liver transplantations)6.2 months(range,2-14.6 months)after a single Y90 treatment.No 90-day mortality was reported.Objective modified response criteria in solid tumors(mRECIST)response were noted in all but one patient.Complete and extensive(50-99%)necrosis was observed in 36%and 45%of tumors,respectively.The post-treatment tumor-absorbed dose significantly differed depending on the extent of pathological necrosis(P=0.045).Median overall survival and progression-free survival(PFS)were respectively of 61.8 months[95%CI:31.4 months-not reached(NR)]and 49.3 months(95%CI:14 months-NR).PFS was longer in patients with complete imaging response[median NR(none recurred or died)vs.21.5 months(95%CI:10.1 months-NR),P<0.001]and in those with complete pathological response[median NR vs.22.5 months(95%CI:10.1 months-NR),P<0.001].Conclusions:Y90 TARE using personalized dosimetry can provide high rates of imaging and pathological response in patients with PVTT,large or multifocal HCC.Subsequent surgery is safe and leads to outcomes far exceeding expectations in an otherwise poor prognosis population with no chance for cure.

Review of therapies for intermediate and advanced stage hepatocellular carcinoma, not suitable for curative therapies: a rapidly changing landscape

Recent clinical trials and new agents have permitted greater clarity in the choice of effective agents for that majority of patients with hepatocellular carcinoma who have advanced disease at diagnosis and thus cannot be offered potentially curative resection,ablation or liver transplantation.The main treatment for these patients remains chemoembolization,although evidence for selective internal radiation therapy(SIRT)with SIR-Spheres or Theraphere,is beginning to suggest that the results with this may be comparable with less toxicity.Patients who have failed chemoembolization or SIRT or have metastatic disease at presentation are suitable for the multikinase inhibitor sorafenib(nexavar)or newly-approved lenvatinib(lenvima)as first line therapies.The choice between which of them to use first is not currently clear.Patients who have failed sorafenib can be offered a choice of FDA-approved regorafenib(stivarga)or immune checkpoint inhibitor nivolumab(opdivo)as second line agents.For that considerable percent of patients presenting with macroscopic portal vein thrombosis,the choice appears to be between multikinase inhibitor or SIRT,given the potential toxicity of chemoembolization in this setting.However,considering the potency of both nivolumab and regorafenib and the pipeline of new agents such as atezolizumab(tecentriq)in current clinical trials,including new immune checkpoint inhibitors,this landscape may change within a couple of years,especially if new evidence arises for the superior effectiveness of combinations of any of these agents over single agents.