Application of selective internal radiotherapy with yttrium-90 microspheres combined with systematic therapy in preoperative transformation therapy of potential resectable colorectal cancer with liver metastasis
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ABSTRACT:
DISEASE(S): Colorectal Cancer With Liver Metastasis
PROVIDER: 86433 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
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Project description:Hepatocellular carcinoma is the most common primary liver cancer and it represents the majority of cancer-related deaths in the world. More than 70% of patients present at an advanced stage, beyond potentially curative options. Ytrrium-90 selective internal radiation therapy (Y90-SIRT) with glass microspheres is rapidly gaining acceptance as a potential therapy for intermediate and advanced stage primary hepatocellular carcinoma and liver metastases. The technique involves delivery of Y90 infused glass microspheres via the hepatic arterial blood flow to the appropriate tumor. The liver tumor receives a highly concentrated radiation dose while sparing the healthy liver parenchyma due to its preferential blood supply from portal venous blood. There are two commercially available devices: TheraSphere® and SIR-Spheres®. Although, Y90-SIRT with glass microspheres improves median survival in patients with intermediate and advanced hepatocellular carcinoma and has the potential to downstage hepatocellular carcinoma so that the selected candidates meet the transplantable criteria, it has not gained widespread acceptance due to the lack of large randomized controlled trials. Currently, there are various clinical trials investigating the use of Y90-SIRT with glass microspheres for treatment of hepatocellular carcinoma and the outcomes of these trials may result in the incorporation of Y90-SIRT with glass microspheres into the treatment guidelines as a standard therapy option for patients with intermediate and advanced stage hepatocellular carcinoma.
| S-EPMC4936170 | biostudies-literature
Project description:Selective internal radiation therapy (SIRT) with microspheres labelled with the β-emitter yttrium-90 (Y-90) enables targeted delivery of radiation to hepatic tumors. SIRT is primarily used to treat inoperable primary or metastatic liver tumors. Eligible patients have usually been exposed to a variety of systemic anticancer therapies, including cytotoxic agents, targeted biologics, immunotherapy and peptide receptor radionuclide therapy (PRRT). All these treatments have potential interactions with SIRT; however, robust evidence on the safety of these potential combinations is lacking. This paper provides current clinical experiences and expert consensus guidelines for the use of SIRT in combination with the anticancer treatment agents likely to be encountered in clinical practice. It was agreed by the expert panel that precautions need to be taken with certain drugs, but that, in general, systemic therapies do not necessarily have to be stopped to perform SIRT. The authors recommend stopping vascular endothelial growth factor inhibitors 4-6 weeks before SIRT, and restart after the patient has recovered from the procedure. It may also be prudent to stop potent radiosensitizers such as gemcitabine therapy 4 weeks before SIRT, and restart treatment at least 2‒4 weeks later. Data from phase III studies combining SIRT with fluorouracil (5FU) or folinic acid/5FU/oxaliplatin (FOLFOX) suggest that hematological toxicity is more common from the combination than it is from chemotherapy without SIRT. There is no evidence to suggest that chemotherapy increases SIRT-specific gastro-intestinal or liver toxicities.
| S-EPMC5750172 | biostudies-literature
Project description:PurposeA multidisciplinary expert panel convened to formulate state-of-the-art recommendations for optimisation of selective internal radiation therapy (SIRT) with yttrium-90 (90Y)-resin microspheres.MethodsA steering committee of 23 international experts representing all participating specialties formulated recommendations for SIRT with 90Y-resin microspheres activity prescription and post-treatment dosimetry, based on literature searches and the responses to a 61-question survey that was completed by 43 leading experts (including the steering committee members). The survey was validated by the steering committee and completed anonymously. In a face-to-face meeting, the results of the survey were presented and discussed. Recommendations were derived and level of agreement defined (strong agreement ≥ 80%, moderate agreement 50%-79%, no agreement ≤ 49%).ResultsForty-seven recommendations were established, including guidance such as a multidisciplinary team should define treatment strategy and therapeutic intent (strong agreement); 3D imaging with CT and an angiography with cone-beam-CT, if available, and 99mTc-MAA SPECT/CT are recommended for extrahepatic/intrahepatic deposition assessment, treatment field definition and calculation of the 90Y-resin microspheres activity needed (moderate/strong agreement). A personalised approach, using dosimetry (partition model and/or voxel-based) is recommended for activity prescription, when either whole liver or selective, non-ablative or ablative SIRT is planned (strong agreement). A mean absorbed dose to non-tumoural liver of 40 Gy or less is considered safe (strong agreement). A minimum mean target-absorbed dose to tumour of 100-120 Gy is recommended for hepatocellular carcinoma, liver metastatic colorectal cancer and cholangiocarcinoma (moderate/strong agreement). Post-SIRT imaging for treatment verification with 90Y-PET/CT is recommended (strong agreement). Post-SIRT dosimetry is also recommended (strong agreement).ConclusionPractitioners are encouraged to work towards adoption of these recommendations.
| S-EPMC8113219 | biostudies-literature
Project description:PurposeTo quantify differences that exist between dosimetry models used for 90Y selective internal radiation therapy (SIRT).Methods and materialsRetrospectively, 37 tumors were delineated on 19 post-therapy quantitative 90Y single photon emission computed tomography/computed tomography scans. Using matched volumes of interest (VOIs), absorbed doses were reported using 3 dosimetry models: glass microsphere package insert standard model (SM), partition model (PM), and Monte Carlo (MC). Univariate linear regressions were performed to predict mean MC from SM and PM. Analysis was performed for 2 subsets: cases with a single tumor delineated (best case for PM), and cases with multiple tumors delineated (typical clinical scenario). Variability in PM from the ad hoc placement of a single spherical VOI to estimate the entire normal liver activity concentration for tumor (T) to nontumoral liver (NL) ratios (TNR) was investigated. We interpreted the slope of the resulting regression as bias and the 95% prediction interval (95%PI) as uncertainty. MCNLsingle represents MC absorbed doses to the NL for the single tumor patient subset; other combinations of calculations follow a similar naming convention.ResultsSM was unable to predict MCTsingle or MCTmultiple (p>.12, 95%PI >±177 Gy). However, SMsingle was able to predict (p<.012) MCNLsingle, albeit with large uncertainties; SMsingle and SMmultiple yielded biases of 0.62 and 0.71, and 95%PI of ±40 and ± 32 Gy, respectively. PMTsingle and PMTmultiple predicted (p<2E-6) MCTsingle and MCTmultiple with biases of 0.52 and 0.54, and 95%PI of ±38 and ± 111 Gy, respectively. The TNR variability in PMTsingle increased the 95%PI for predicting MCTsingle (bias = 0.46 and 95%PI = ±103 Gy). The TNR variability in PMTmultiple modified the bias when predicting MCTmultiple (bias = 0.32 and 95%PI = ±110 Gy).ConclusionsThe SM is unable to predict mean MC tumor absorbed dose. The PM is statistically correlated with mean MC, but the resulting uncertainties in predicted MC are large. Large differences observed between dosimetry models for 90Y SIRT warrant caution when interpreting published SIRT absorbed doses. To reduce uncertainty, we suggest the entire NL VOI be used for TNR estimates when using PM.
| S-EPMC5085875 | biostudies-literature
Project description:PurposeSelective internal radiation therapy (SIRT) is administered to treat tumors of the liver and is generally well tolerated. Although widely adopted for its therapeutic benefits, SIRT is rarely combined with external beam radiation therapy (EBRT) owing to the complexity of the dosimetry resulting from the combination of treatments with distinct radiobiological effects. The purpose of this study was to establish a dosimetric framework for combining SIRT and EBRT using clinical experience derived from representative patients with hepatocellular carcinoma (HCC) who received both therapies.Methods and materialsTreatments from 10 patients with HCC given EBRT either before or after SIRT were analyzed. The dosimetry framework used here considered differences in the radiobiological effects and fractionation schemes of SIRT versus EBRT, making use of the concepts of biological effective dose (BED) and equivalent dose (EQD). Absorbed dose from SIRT was calculated, converted to BED, and summed with BED from EBRT dose plans. Two of these patients were used in a virtual planning exercise to investigate the feasibility of combining stereotactic body radiation therapy and SIRT.ResultsThe combination of EBRT and SIRT in 10 patients with HCC showed no major toxicity. No Child-Pugh scores went above 8 and albumin-bilirubin scores from only 1 patient worsened to grade 3 (> -1.39) from treatment through 3-months follow-up. A framework with radiobiological modeling was developed to manage the combined treatments in terms of their sum BED. The exploratory SIRT plus SABR inverse dose plans for 2 patients, incorporating radiobiologically informed 90Y SIRT dosimetry, achieved dose distributions comparable to SBRT alone.ConclusionsTreatment with both EBRT and SIRT can be given safely to patients with HCC. The BED and EQD concepts should be used in combined dosimetry to account for the differing radiobiological effects of EBRT and SIRT. Inverse dose planning of EBRT after SIRT could provide improved dose distributions and flexibility to the clinical workflow. Further research into combination therapy is needed through prospective trials.
| S-EPMC8071732 | biostudies-literature
Project description:IntroductionThis investigator-initiated clinical trial aims to study the efficacy and safety of administering selective internal radiation therapy with resin yttrium-90 microspheres (SIRT) followed by standard chemotherapy in unresectable intrahepatic cholangiocarcinoma (ICC).MethodsA phase 2 single-arm multicenter study was conducted in patients with unresectable ICC (NCT02167711). SIRT was administered at dose of 120 Gy targeted at tumor followed by commencement of gemcitabine 1,000 mg/m2 and cisplatin 25 mg/m2 on days one and eight of a 21-day cycle. The primary endpoint was overall survival (OS), and the secondary endpoints include progression-free survival (PFS), response rate according to Response Evaluation Criteria in solid tumors 1.1, toxicity, and time from SIRT to commencement of chemotherapy.ResultsTotal 31 patients were screened and twenty-four were recruited. All patients completed SIRT and 16 of them underwent subsequent chemotherapy. The median cycle of chemotherapy was 5 (range: 1-8). The median OS was 13.6 months (95% CI: 5.4-21.6) for the intent-to-treat population. Among 16 patients undergoing chemotherapy, the median OS was 21.6 months (95% CI: 7.3-25.2) and the median PFS was 9 months (95% CI: 3.2-13.1). The response rate was 25% (95% CI: 3.8-46.2%), and the disease control rate was 75% (95% CI: 53.8-96.2%). No new safety signal was observed, with fewer than 10% of patients suffering from grade 3 or higher treatment-related adverse events. The median time from SIRT to chemotherapy was 29 (range: 7-42) days. Eight patients could not receive chemotherapy due to rapid progressive disease (n = 4), underlying treatment unrelated comorbidities (n = 2), and withdrawal of consent due to personal reasons (n = 2).ConclusionsTreatment of SIRT followed by standard gemcitabine and cisplatin chemotherapy is feasible and effective for unresectable ICC. Further studies are required to study the optimal sequence of SIRT and chemotherapy.
| S-EPMC9485918 | biostudies-literature
Project description:To evaluate the efficacy and safety of yttrium-90 carbon microspheres in patients with unresectable colorectal liver metastases
| 5569 | ecrin-mdr-crc
Project description:IntroductionThis literature review and exploratory network meta-analysis (NMA) aimed to compare the clinical effectiveness and tolerability of selective internal radiation therapy (SIRT) using yttrium-90 (Y-90) resin microspheres, regorafenib (REG), trifluridine-tipiracil (TFD/TPI), and best supportive care (BSC) in adult patients with chemotherapy-refractory or chemotherapy-intolerant metastatic colorectal cancer (mCRC).MethodsIn light of recently published data, the literature was searched to complement and update a review published in 2018. Studies up to December 2022 comparing two or more of the treatments and reporting overall survival (OS), progression-free survival (PFS), or incidence of adverse events (AE) were included. The NMA compared hazard ratios (HRs) for OS and PFS using Markov chain Monte Carlo techniques.ResultsFifteen studies were included, with eight studies added (none addressing SIRT). All active treatments improved OS in relation to BSC. SIRT had the longest OS among all treatments, although without statistically significant differences (HR [95% credible interval] for SIRT, 0.48 [0.27, 0.87]; TFD/TPI, 0.62 [0.46, 0.83]; REG, 0.78 [0.57, 1.05]) in a fixed effects model. Information regarding SIRT was insufficient for PFS analysis, and TFD/TPI was the best intervention (HR 2.26 [1.6, 3.18]). One SIRT study reported radioembolization-induced liver disease in > 10% of the sample; this was symptomatically managed. Non-haematological AEs (hand-foot skin reaction, fatigue, diarrhoea, hypertension, rash or desquamation) were more common with REG, while haematological events (neutropoenia, leukopenia, and anaemia) were more common with TFD/TPI.ConclusionCurrent evidence supports SIRT treatment in patients with chemotherapy-refractory or chemotherapy-intolerant mCRC compared to newer oral agents, with comparable OS and low incidence of AEs.
| S-EPMC10960912 | biostudies-literature
Project description:This is a prospective pilot study designed to document safety and efficacy of liver-directed therapy for colorectal, neuroendocrine, cholangiocarcinoma, melanoma, and breast cancer metastases to the liver using Yttrium-90 glass microspheres (TheraSphere).
| 2101871 | ecrin-mdr-crc
Project description:Due to the wide application of rare earth oxides nanoparticles in different fields, they will inevitably be released into the environment, and their potential toxicity and ecological risks in the environment have become a concern of people. Yttrium oxide nanoparticles are important members of rare earth oxides nanoparticles. The molecular mechanism of its influence on plant growth and development and plant response to them is unclear. In this study, we found that yttrium oxide nanoparticles above 2 mM significantly inhibited the growth of Arabidopsis seedlings. Using the Arabidopsis marker lines reflecting auxin signal, it was found that the treatment of yttrium oxide nanoparticles led to the disorder of auxin signal in root cells: the auxin signal in quiescent center cells and columella stem cells decreased; while the auxin signal in the stele cells was enhanced. In addition, trypan blue staining showed that yttrium oxide nanoparticles caused the death of root cells. Transcriptome sequencing analysis showed that yttrium oxide nanoparticles specifically inhibited the expression of lignin synthesis related genes, activated mitogen-activated protein kinase (MAPK) signaling pathway, and enhanced ethylene and ABA signaling pathways in plants. This study revealed the phytotoxicity of yttrium oxide nanoparticles at the molecular level, and provided a new perspective at the molecular level for plants to respond to rare earth oxide stress.
2022-10-05 | GSE214612 | GEO