|
1
|
Calatayud-Jordán J, Carrasco-Vela N, Chimeno-Hernández J, Carles-Fariña M, Olivas-Arroyo C, Bello-Arqués P, Pérez-Enguix D, Martí-Bonmatí L, Torres-Espallardo I. Y-90 PET/MR imaging optimization with a Bayesian penalized likelihood reconstruction algorithm. Phys Eng Sci Med 2024; 47:1397-1413. [PMID: 38884672 DOI: 10.1007/s13246-024-01452-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2024] [Accepted: 05/23/2024] [Indexed: 06/18/2024]
Abstract
Positron Emission Tomography (PET) imaging after90 Y liver radioembolization is used for both lesion identification and dosimetry. Bayesian penalized likelihood (BPL) reconstruction algorithms are an alternative to ordered subset expectation maximization (OSEM) with improved image quality and lesion detectability. The investigation of optimal parameters for90 Y image reconstruction of Q.Clear, a commercial BPL algorithm developed by General Electric (GE), in PET/MR is a field of interest and the subject of this study. The NEMA phantom was filled at an 8:1 sphere-to-background ratio. Acquisitions were performed on a PET/MR scanner for clinically relevant activities between 0.7 and 3.3 MBq/ml. Reconstructions with Q.Clear were performed varying the β penalty parameter between 20 and 6000, the acquisition time between 5 and 20 min and pixel size between 1.56 and 4.69 mm. OSEM reconstructions of 28 subsets with 2 and 4 iterations with and without Time-of-Flight (TOF) were compared to Q.Clear with β = 4000. Recovery coefficients (RC), their coefficient of variation (COV), background variability (BV), contrast-to-noise ratio (CNR) and residual activity in the cold insert were evaluated. Increasing β parameter lowered RC, COV and BV, while CNR was maximized at β = 4000; further increase resulted in oversmoothing. For quantification purposes, β = 1000-2000 could be more appropriate. Longer acquisition times resulted in larger CNR due to reduced image noise. Q.Clear reconstructions led to higher CNR than OSEM. A β of 4000 was obtained for optimal image quality, although lower values could be considered for quantification purposes. An optimal acquisition time of 15 min was proposed considering its clinical use.
Collapse
Affiliation(s)
- José Calatayud-Jordán
- Department of Nuclear Medicine, La Fe University and Polytechnical Hospital, Av. Fernando Abril Martorell 106, 46026, Valencia, Spain.
| | - Nuria Carrasco-Vela
- Radiophysics and Radiological Protection Service, Clinical University Hospital of Valencia, Av. Blasco Ibáñez 17, 46010, Valencia, Spain
| | - José Chimeno-Hernández
- Department of Nuclear Medicine, La Fe University and Polytechnical Hospital, Av. Fernando Abril Martorell 106, 46026, Valencia, Spain
| | - Montserrat Carles-Fariña
- Biomedical Imaging Research Group (GIBI230) at Health Research Institute Hospital La Fe (IIS La Fe), La Fe University and Polytechnical Hospital, Av. Fernando Abril Martorell 106, 46026, Valencia, Spain
| | - Consuelo Olivas-Arroyo
- Department of Nuclear Medicine, La Fe University and Polytechnical Hospital, Av. Fernando Abril Martorell 106, 46026, Valencia, Spain
| | - Pilar Bello-Arqués
- Department of Nuclear Medicine, La Fe University and Polytechnical Hospital, Av. Fernando Abril Martorell 106, 46026, Valencia, Spain
| | - Daniel Pérez-Enguix
- Department of Radiology, La Fe University and Polytechnical Hospital, Av. Fernando Abril Martorell 106, 46026, Valencia, Spain
| | - Luis Martí-Bonmatí
- Biomedical Imaging Research Group (GIBI230) at Health Research Institute Hospital La Fe (IIS La Fe), La Fe University and Polytechnical Hospital, Av. Fernando Abril Martorell 106, 46026, Valencia, Spain
- Department of Radiology, La Fe University and Polytechnical Hospital, Av. Fernando Abril Martorell 106, 46026, Valencia, Spain
| | - Irene Torres-Espallardo
- Department of Nuclear Medicine, La Fe University and Polytechnical Hospital, Av. Fernando Abril Martorell 106, 46026, Valencia, Spain
- Biomedical Imaging Research Group (GIBI230) at Health Research Institute Hospital La Fe (IIS La Fe), La Fe University and Polytechnical Hospital, Av. Fernando Abril Martorell 106, 46026, Valencia, Spain
| |
Collapse
|
|
2
|
Finger PT. High-Dose-Rate Yttrium-90 ( 90Y) Episcleral Plaque Brachytherapy for Iris and Iridociliary Melanoma. OPHTHALMOLOGY SCIENCE 2024; 4:100513. [PMID: 38840779 PMCID: PMC11152663 DOI: 10.1016/j.xops.2024.100513] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/14/2024] [Revised: 02/20/2024] [Accepted: 03/11/2024] [Indexed: 06/07/2024]
Abstract
Purpose To describe a pilot study on the use of single-session, high-dose-rate, Food and Drug Administration-cleared, yttrium-90 (Y90) plaque brachytherapy for iris and iridociliary melanoma. Design A single-center, clinical case series. Participants Six consecutive patients were included in this study. Each was diagnosed with an iris or iridociliary melanoma based on clinical examination with or without biopsy. Methods Each tumor was staged according to the American Joint Committee on Cancer criteria and received Y90 eye plaque brachytherapy. The main variables were tumor size, patient age, sex, and method of diagnosis (clinical or biopsy). Surgical techniques, treatment durations, and ocular side effects were recorded. Local control was defined as a lack of tumor growth or regression determined by clinical examinations, including slit-lamp and gonio photography, as well as high-frequency ultrasound measurements. Toxicity parameters included acute and short-term corneal/scleral change, anterior segment inflammation, and cataract progression. Main Outcome Measures Local and systemic cancer control, tumor regression, visual acuity, as well as radiation-related normal tissue toxicity. Results High-dose-rate Y90 plaque brachytherapy was used to treat small (American Joint Committee on Cancer cT1) category melanomas. Single-surgery high-dose-rate irradiations were performed under anesthesia. Because of short treatment durations, high-dose-rate Y90 did not require the additional procedures used for low-dose-rate plaque (e.g., sutures, amniotic membrane epicorneal buffering, Gunderson flaps, and second surgeries for plaque removal). Only conjunctival recession was used to avoid normal tissue irradiation. High-dose-rate Y90 treatment durations averaged 8.8 minutes (median, 7.9; range, 5.8-12.9). High-dose-rate Y90 brachytherapy was associated with no periorbital, corneal (Descemet folds), or conjunctival edema. There was no acute or short-term anterior uveitis, secondary cataract, scleropathy, radiation retinopathy, maculopathy, or optic neuropathy. The follow-up was a mean of 16.0 (range 12-24) months. Evidence of local control included a lack of expansion of tumor borders (n = 6, 100%), darkening with or without atrophy of the tumor surface (n = 5/6, 83%), and a mean 24.5% reduction in ultrasonographically measured tumor thickness. There were no cases of metastatic disease. Conclusions High-dose-rate Y90 brachytherapy allowed for single-surgery, minimally invasive, outpatient irradiation of iris and iridociliary melanomas. Financial Disclosures Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
Collapse
Affiliation(s)
- Paul T. Finger
- The Department of Ocular Tumor, Orbital Disease, and Ophthalmic Radiation Therapy, The New York Eye Cancer Center, New York, New York
| |
Collapse
|
|
3
|
Mehadji B, Ruvalcaba CA, Hernandez AM, Abdelhafez YG, Goldman R, Roncali E. Translating contrast enhanced computed tomography images to liver radioembolization dose distribution for more comprehensively indicating patients. Phys Med Biol 2024; 69:165016. [PMID: 39048102 DOI: 10.1088/1361-6560/ad6748] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2024] [Accepted: 07/23/2024] [Indexed: 07/27/2024]
Abstract
Objective.Contrast-enhanced computed tomography (CECT) is commonly used in the pre-treatment evaluation of liver Y-90 radioembolization feasibility. CECT provides detailed imaging of the liver and surrounding structures, allowing healthcare providers to assess the size, location, and characteristics of liver tumors prior to the treatment. Here we propose a method for translating CECT images to an expected dose distribution for tumor(s) and normal liver tissue.Approach.A pre-procedure CECT is used to obtain an iodine arterial-phase distribution by subtracting the non-contrast CT from the late arterial phase. The liver segments surrounding the targeted tumor are selected using Couinaud's method. The resolution of the resulting images is then degraded to match the resolution of the positron emission tomography (PET) images, which can image the Y-90 activity distribution post-treatment. The resulting images are then used in the same way as PET images to compute doses using the local deposition method. CECT images from three patients were used to test this method retrospectively and were compared with Y-90 PET-based dose distributions through dose volume histograms.Main results.Results show a concordance between predicted and delivered Y-90 dose distributions with less than 10% difference in terms of mean dose, for doses greater than 10% of the 98th percentile (D2%).Significance.CECT-derived predictions of Y-90 radioembolization dose distributions seem promising as a supplementary tool for physicians when assessing treatment feasibility. This dosimetry prediction method could provide a more comprehensive pre-treatment evaluation-offering greater insights than a basic assessment of tumor opacification on CT images.
Collapse
Affiliation(s)
- Brahim Mehadji
- Department of Radiology, University of California, Davis, Sacramento, CA, United States of America
| | - Carlos A Ruvalcaba
- Department of Department of Biomedical Engineering, University of California, Davis, Davis, CA, United States of America
| | - Andrew M Hernandez
- Department of Radiology, University of California, Davis, Sacramento, CA, United States of America
| | - Yasser G Abdelhafez
- Department of Radiology, University of California, Davis, Sacramento, CA, United States of America
| | - Roger Goldman
- Department of Radiology, University of California, Davis, Sacramento, CA, United States of America
| | - Emilie Roncali
- Department of Radiology, University of California, Davis, Sacramento, CA, United States of America
- Department of Department of Biomedical Engineering, University of California, Davis, Davis, CA, United States of America
| |
Collapse
|
|
4
|
Finger PT. Yttrium-90 Episcleral Plaque Brachytherapy for Choroidal Melanoma. JOURNAL OF VITREORETINAL DISEASES 2024; 8:210-214. [PMID: 38465362 PMCID: PMC10924596 DOI: 10.1177/24741264241227684] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 03/12/2024]
Abstract
Purpose: To describe the first use of high-dose-rate yttrium-90 disc brachytherapy for choroidal melanoma. Methods: A 72-year-old patient had a cT1-category choroidal melanoma characterized by the presence of orange pigment, increasing subretinal fluid (SRF), and enlarging tumor thickness. It was treated with single-session, light-guided, light-defined yttrium-90-disc brachytherapy. Results: A specialized handheld applicator provided with 4 encircling lights was used to guide plaque placement and localize treatment. Unlike low-dose-rate plaques, high-dose-rate yttrium-90 required only 3 minutes 39 seconds. In this case, treatment did not require episcleral sutures, muscle relocation, outpatient dwell time, or a second surgery. High-dose-rate treatment improved radiation safety by eliminating perioperative exposure to health care personnel, the community, and the family. At the 13-month follow-up, the SRF and tumor thickness were diminished. There was no secondary cataract, radiation retinopathy, maculopathy, or optic neuropathy, and the visual acuity was 20/20. Conclusions: Yttrium-90 brachytherapy allowed for single-surgery, minimally invasive, outpatient irradiation of a choroidal melanoma.
Collapse
|
|
5
|
Jiang Z, Yang F, Wang W. Applications of Yttrium-90 ( 90Y) in Hepatocellular Carcinoma. Onco Targets Ther 2024; 17:149-157. [PMID: 38414759 PMCID: PMC10898254 DOI: 10.2147/ott.s445898] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2023] [Accepted: 02/17/2024] [Indexed: 02/29/2024] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common primary liver cancer, affecting millions of people worldwide. Due to the lack of systemic radiation therapy in hepatocellular carcinoma, researchers have been investigating the use of yttrium-90 (90Y) radioembolization for local-regional tumor control since the 1960s. With the development of glass and resin 90Y microspheres and the durable local control, good long-term efficacy, and equivalent tumor responsiveness and tolerability of 90Y-selective internal irradiation compared with alternative therapies such as transarterial chemoembolization (TACE) and sorafenib, 90Y radioembolization has gradually been applied in the treatment of hepatocellular carcinoma of all stages. In this article, we summarize the latest progress of 90Y in the treatment of hepatocellular carcinoma in terms of its principle, advantages, indications, contraindications, efficacy and adverse effects.
Collapse
Affiliation(s)
- ZhongHao Jiang
- Inner Mongolia Medical University, Department of Hepatobiliary Surgery, Affiliated Hospital of Inner Mongolia Medical University, Inner Mongolia, 010050, People’s Republic of China
| | - Fan Yang
- Inner Mongolia Medical University, Department of Hepatobiliary Surgery, Affiliated Hospital of Inner Mongolia Medical University, Inner Mongolia, 010050, People’s Republic of China
| | - WanXiang Wang
- Inner Mongolia Medical University, Department of Hepatobiliary Surgery, Affiliated Hospital of Inner Mongolia Medical University, Inner Mongolia, 010050, People’s Republic of China
| |
Collapse
|
|
6
|
Finger PT, Stewart R, Rivard MJ, Beers RJ, Kamen J, Lama S, Chin KJ, Mohney K, Welles TS, Sauerwein WAG, Rosenzweig K. First clinical implementation of Yttrium-90 Disc Brachytherapy after FDA clearance. Brachytherapy 2023; 22:416-427. [PMID: 36948988 DOI: 10.1016/j.brachy.2023.02.004] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2022] [Revised: 01/04/2023] [Accepted: 02/15/2023] [Indexed: 03/24/2023]
Abstract
PURPOSE Herein, we study if high-dose-rate (HDR) yttrium-90 (90Y) brachytherapy could be utilized by medical physicists, radiation oncologists, and ophthalmic surgeons. METHODS AND MATERIALS Yttrium-90 (90Y) beta-emitting brachytherapy sources received United States Food and Drug Administration clearance for episcleral treatment of ocular tumors and benign growths. Dose calibration traceable to the National Institute of Standards and Technology as well as treatment planning and target delineation methods were established. Single-use systems included a 90Y-disc affixed within specialized, multifunction, handheld applicator. Low-dose-rate to high-dose-rate prescription conversions and depth-dose determinations were performed. Radiation safety was evaluated based on live exposure rates during assembly and surgeries. Clinical data for radiation safety, treatment tolerability, and local control was collected. RESULTS Practice parameters for the medical physicist, radiation oncologist, and ophthalmic surgeon were defined. Device sterilizations, calibrations, assemblies, surgical methods, and disposals were reproducible and effective. Treated tumors included iris melanoma, iridociliary melanoma, choroidal melanoma, and a locally invasive squamous carcinoma. Mean calculated 90Y disc activity was 14.33 mCi (range 8.8-16.6), prescription dose 27.8 Gy (range 22-30), delivered to depth of 2.3 mm (range 1.6-2.6), at treatment durations of 420 s (7.0 min, range 219 s-773 s). Both insertion and removal were performed during one surgical session. After surgery, each disc-applicator- system was contained for decay in storage. Treatments were well-tolerated. CONCLUSIONS HDR 90Y episcleral brachytherapy devices were created, implementation methods developed, and treatments performed on 6 patients. Treatments were single-surgery, rapid, and well-tolerated with short-term follow up.
Collapse
Affiliation(s)
- Paul T Finger
- The Department of Ocular Tumor, Orbital Disease, and Ophthalmic Radiation Therapy, The New York Eye Cancer Center, New York, NY; The Departments of Ophthalmology, Radiation Oncology, and Radiation Safety, New York Eye and Ear Infirmary of Mount Sinai and Icahn School of Medicine at Mount Sinai, New York, NY; Scientific Advisory Board and Employees of Liberty Vision Corporation, Portsmouth, NH.
| | - Robert Stewart
- The Departments of Ophthalmology, Radiation Oncology, and Radiation Safety, New York Eye and Ear Infirmary of Mount Sinai and Icahn School of Medicine at Mount Sinai, New York, NY
| | - Mark J Rivard
- Scientific Advisory Board and Employees of Liberty Vision Corporation, Portsmouth, NH
| | - Raymond J Beers
- The Departments of Ophthalmology, Radiation Oncology, and Radiation Safety, New York Eye and Ear Infirmary of Mount Sinai and Icahn School of Medicine at Mount Sinai, New York, NY
| | - Jacob Kamen
- The Departments of Ophthalmology, Radiation Oncology, and Radiation Safety, New York Eye and Ear Infirmary of Mount Sinai and Icahn School of Medicine at Mount Sinai, New York, NY
| | - Shyam Lama
- The Departments of Ophthalmology, Radiation Oncology, and Radiation Safety, New York Eye and Ear Infirmary of Mount Sinai and Icahn School of Medicine at Mount Sinai, New York, NY
| | - Kimberly J Chin
- The Department of Ocular Tumor, Orbital Disease, and Ophthalmic Radiation Therapy, The New York Eye Cancer Center, New York, NY; Scientific Advisory Board and Employees of Liberty Vision Corporation, Portsmouth, NH
| | - Kyle Mohney
- Scientific Advisory Board and Employees of Liberty Vision Corporation, Portsmouth, NH
| | - Toby S Welles
- Scientific Advisory Board and Employees of Liberty Vision Corporation, Portsmouth, NH
| | | | - Kenneth Rosenzweig
- The Departments of Ophthalmology, Radiation Oncology, and Radiation Safety, New York Eye and Ear Infirmary of Mount Sinai and Icahn School of Medicine at Mount Sinai, New York, NY
| |
Collapse
|
|
7
|
Shah HJ, Ruppell E, Bokhari R, Aland P, Lele VR, Ge C, McIntosh LJ. Current and upcoming radionuclide therapies in the direction of precision oncology: A narrative review. Eur J Radiol Open 2023; 10:100477. [PMID: 36785643 PMCID: PMC9918751 DOI: 10.1016/j.ejro.2023.100477] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2022] [Revised: 11/30/2022] [Accepted: 12/13/2022] [Indexed: 02/01/2023] Open
Abstract
As new molecular tracers are identified to target specific receptors, tissue, and tumor types, opportunities arise for the development of both diagnostic tracers and their therapeutic counterparts, termed "theranostics." While diagnostic tracers utilize positron emitters or gamma-emitting radionuclides, their theranostic counterparts are typically bound to beta and alpha emitters, which can deliver specific and localized radiation to targets with minimal collateral damage to uninvolved surrounding structures. This is an exciting time in molecular imaging and therapy and a step towards personalized and precise medicine in which patients who were either without treatment options or not candidates for other therapies now have expanded options, with tangible data showing improved outcomes. This manuscript explores the current state of theranostics, providing background, treatment specifics, and toxicities, and discusses future potential trends.
Collapse
Affiliation(s)
- Hina J. Shah
- Department of Radiology, Division of Nuclear Medicine, Brigham and Women’s Hospital, Boston, MA 02115, USA,Department of Imaging, Dana-Farber Cancer Institute, Boston, MA 02115, USA,Corresponding author at: Department of Radiology, Division of Nuclear Medicine, Brigham and Women’s Hospital, Boston, MA 02115, USA.
| | - Evan Ruppell
- Department of Radiology, University of Massachusetts Chan Medical School, Memorial Health Care, Worcester, MA 01655, USA
| | - Rozan Bokhari
- Department of Radiology, Beth Israel Lahey Health, Burlington, MA 01803, USA
| | - Parag Aland
- In-charge Nuclear Medicine and PET/CT, Infinity Medical Centre, Mumbai, Maharashtra 400015, India
| | - Vikram R. Lele
- Chief, Department of Nuclear Medicine and PET/CT, Jaslok Hospital and Research Centre, Mumbai, Maharashtra 400026, India
| | - Connie Ge
- University of Massachusetts Chan Medical School, Worcester, MA 01655, USA
| | - Lacey J. McIntosh
- Division of Oncologic and Molecular Imaging, University of Massachusetts Chan Medical School / Memorial Health Care, Worcester, MA 0165, USA
| |
Collapse
|
|
8
|
Zefzoufi M, Fdil R, Bouamama H, Gadhi C, Katakura Y, Mouzdahir A, Sraidi K. Effect of extracts and isolated compounds derived from Retama monosperma (L.) Boiss. on anti-aging gene expression in human keratinocytes and antioxidant activity. JOURNAL OF ETHNOPHARMACOLOGY 2021; 280:114451. [PMID: 34314805 DOI: 10.1016/j.jep.2021.114451] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/16/2021] [Revised: 07/14/2021] [Accepted: 07/23/2021] [Indexed: 06/13/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Moroccan folk medicine treats skin cicatrization with Retama monosperma (L.) Boiss. locally named "Rtem", but the mechanism involved is still not well known. Traditional healers use the plant in small doses as an anthelmintic, disinfectant and an effective abortive. In addition, the cladodes powder mixed with honey is employed as purgative and vermifuge. Equally, the SIRT1 and SIRT3 genes activation and sirtuin proteins expression, which delay cellular senescence, participate in wound healing and skin regeneration especially, SIRT1 the most studied gene, leads to fast skin restoration and cicatrization. AIM OF THE STUDY In this study, we evaluated the ability of the Retama monosperma (L.)Boiss. flowers and seeds extracts and the isolated compounds in augmenting the SIRT1 and SIRT3 gene expression in HaCaT cells and expressing the antioxidant activity. MATERIALS AND METHODS We examined for quantitative expression levels of SIRT1 and SIRT3 in HaCaT cell by qRT-PCR and the antioxidant activity by four tests (conjugated diene, TBARS assay, DPPH scavenging activity and H2O2 radical scavenging assay) of diethyl ether extract of flowers (DEF extract) and ethyl acetate extract of seeds (EAS extract) of R. monosperma(L.) Boiss. and the isolated compounds (quercetin, 6-methoxykaempferol, kaempferol and genistein). RESULTS The screening system by EGFP fluorescence revealed that all samples and resveratrol significantly increase SIRT1 and SIRT3 promoters activities in HaCaT cells with p< 0.05. Furthermore, EAS, quercetin, 6-methoxykaempferol and kaempferol increase significantly (p< 0.05) SIRT1 (3.43, 1.18, 2.62, and 1.72 expression quantity, respectively) and SIRT3 (16.27, 5.01, 3.01, and 6.18 expression quantity, respectively) in HaCaT cells. On the other hand, genistein has a moderate activity on SIRT1 and SIRT3 with 1.43 and 2.04 expression levels. For the antioxidant activity, the EAS and the pure compounds exhibited stronger antioxidant activity than BHT. While DEF and genistein have a moderate antioxidant activity when compared with BHT. CONCLUSIONS In this study, the expression levels of SIRT1 and SIRT3 in HaCaT cells increase in the presence of extracts of R. monosperma (L.) Boiss. and the pure compounds.
Collapse
Affiliation(s)
- Manal Zefzoufi
- Laboratory of Bioorganic Chemistry, Faculty of Sciences, University Chouaïb Doukkali, Jabran Khalil Jabran Avenue, PO Box: 299, El Jadida, 24000, Morocco; Laboratory of Sustainable Development and Health Research, Faculty of Sciences and Techniques, Cadi Ayyad University, Abdelkarim AlKhattabi Avenue, PO. Box: 549, Marrakech, 40000, Morocco.
| | - Rabiaa Fdil
- Laboratory of Bioorganic Chemistry, Faculty of Sciences, University Chouaïb Doukkali, Jabran Khalil Jabran Avenue, PO Box: 299, El Jadida, 24000, Morocco.
| | - Hafida Bouamama
- Laboratory of Sustainable Development and Health Research, Faculty of Sciences and Techniques, Cadi Ayyad University, Abdelkarim AlKhattabi Avenue, PO. Box: 549, Marrakech, 40000, Morocco.
| | - Chemseddoha Gadhi
- Laboratory of Agri-Food, Biotechnology; and Valorisation of Plant Resources, Faculty of Sciences Semlalia, Cadi Ayyad University, PO. Box 2390; My Abdellah BD., Marrakech, 40000, Morocco.
| | - Yoshinori Katakura
- Laboratory of Cellular Regulation Technology, Faculty of Agriculture, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka, 819-0395, Japan.
| | - Abdelkarim Mouzdahir
- Laboratory of Bioorganic Chemistry, Faculty of Sciences, University Chouaïb Doukkali, Jabran Khalil Jabran Avenue, PO Box: 299, El Jadida, 24000, Morocco.
| | - Khadija Sraidi
- Laboratory of Bioorganic Chemistry, Faculty of Sciences, University Chouaïb Doukkali, Jabran Khalil Jabran Avenue, PO Box: 299, El Jadida, 24000, Morocco.
| |
Collapse
|
|
9
|
Radhakrishnan ER, Chirayil V, Pandiyan A, Subramanian S, Mallia MB, Kamaleshwaran KK, Shinto A. Preparation of Rhenium-188-Lipiodol Using Freeze-Dried Kits for Transarterial Radioembolization: An Overview and Experience in a Hospital Radiopharmacy. Cancer Biother Radiopharm 2021; 37:63-70. [PMID: 34101501 DOI: 10.1089/cbr.2021.0043] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
Background: Rhenium-188-lipiodol is a clinically effective, economically viable radiopharmaceutical for Selective Internal Radiation Therapy of liver cancer. Present study evaluates the performance of three freeze-dried kits with respect to the radiochemistry, quality control, and overall "ease of preparation" aspects in a hospital radiopharmacy. Materials and Methods: Freeze-dried kits of acetylated 4-hexadecyl-4,7-diaza-1,10-decanedithiol (AHDD), super six sulfur (SSS), and diethyl dithiocarbamate (DEDC), obtained commercially or received as gift, were used for the preparation of Rhenium-188-lipiodol using freshly eluted 188Re-sodium perrhenate from commercial Tungsten-188/Rhenium-188 generator following recommended procedures. Results: The overall yield of Rhenium-188-lipiodol prepared using AHDD Kit, SSS Kit, and DEDC Kit was 74.82% ± 3.3%, 87.55% ± 4.8%, and 76.38% ± 4.6%, respectively. Observed radiochemical purity (RCP) of Rhenium-188-lipiodol prepared using these kits was 88.65% ± 2.8%, 92.92% ± 3.0%, and 91.38% ± 3.0%, respectively. Using a modified version of the DEDC Kits, overall yield of 87.17% ± 2.7% and RCP of 95.43% ± 2.3% could be achieved. Conclusions: While all three freeze-dried kits can be used for the preparation of Rhenium-188-lipiodol in >70% overall yield, the modified version of DEDC Kits has some advantages in terms of preparation time and volume of Rhenium-188 activity that can be added to the kit vial. The latter feature of the DEDC Kit is particularly useful for patient dose preparation with Rhenium-188 activity of low radioactive concentration.
Collapse
Affiliation(s)
| | - Viju Chirayil
- Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Mumbai, India
| | - Arun Pandiyan
- Kovai Medical Centre and Hospital, Coimbatore, India
| | - Suresh Subramanian
- Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Mumbai, India
| | - Madhava B Mallia
- Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Mumbai, India.,Homi Bhabha National Institute, Mumbai, India
| | | | | |
Collapse
|
|
10
|
Selective Internal Radiation Therapy for Hepatocellular Carcinoma Across the Barcelona Clinic Liver Cancer Stages. Dig Dis Sci 2021; 66:899-911. [PMID: 32281043 DOI: 10.1007/s10620-020-06245-y] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2019] [Accepted: 03/29/2020] [Indexed: 02/08/2023]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is the second most common lethal cancer, and there is a need for effective therapies. Selective internal radiation therapy (SIRT) has been increasingly used, but is not supported by guidelines due to a lack of solid evidence. AIMS Determine the efficacy and safety of SIRT in HCC across the Barcelona Clinic Liver Cancer (BCLC) stages A, B, and C. METHODS Consecutive patients that received SIRT between 2006 and 2016 at two centers in Canada were evaluated. RESULTS We analyzed 132 patients, 12 (9%), 62 (47%), and 58 (44%) belonged to BCLC stages A, B, and C; mean age was 61.2 (SD ± 9.2), and 89% were male. Median survival was 12.4 months (95% CI 9.6-16.6), and it was different across the stages: 59.7 (95% CI NA), 12.8 (95% CI 10.2-17.5), and 9.3 months (95% CI 5.9-11.8) in BCLC A, B, and C, respectively (p = 0.009). Independent factors associated with survival were previous HCC treatment (HR 2.01, 95% CI 1.23-3.27, p = 0.005), bi-lobar disease (HR 2.25, 95% CI 1.30-3.89, p = 0.003), ascites (HR 1.77, 95% CI 0.99-3.13, p = 0.05), neutrophil-to-lymphocyte ratio (HR 1.11, 95% CI 1.02-1.20, p = 0.01), Albumin-Bilirubin (ALBI) grade-3 (HR 2.69, 95% CI 1.22-5.92, p = 0.01), tumor thrombus (HR 2.95, 95% CI 1.65-5.24, p < 0.001), and disease control rate (HR 0.62, 95% CI 0.39-0.96, p = 0.03). Forty-four (33%) patients developed severe adverse events, and ALBI-3 was associated with higher risk of these events. CONCLUSIONS SIRT has the potential to be used across the BCLC stages in cases with preserved liver function. When using it as a rescue treatment, one should consider variables reflecting liver function, HCC extension, and systemic inflammation, which are associated with mortality.
Collapse
|
|
11
|
Patel R, Roberson J, Prakash D, Meyer R, Hogan L, Azmy C, Suprenant V, Ryu S, Stessin A. Potential alternative treatment approach for pediatric patient with diffusely infiltrative primary rhabdomyosarcoma of the liver. Rep Pract Oncol Radiother 2021; 26:143-148. [PMID: 34046225 PMCID: PMC8149128 DOI: 10.5603/rpor.a2021.0008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2020] [Accepted: 12/24/2020] [Indexed: 11/25/2022] Open
Abstract
Primary hepatic rhabdomyosarcoma is rare, making decisions regarding locoregional management with resection and/or conventional radiation difficult. We present a novel treatment approach for a pediatric patient diagnosed with rhabdomyosarcoma diffusely involving the liver. This patient underwent treatment with yttrium-90 (Y-90) microspheres followed by external beam radiation therapy (EBRT ) to residual disease, interdigitated with systemic chemotherapy. Initial post-radiation imaging showed significant response to treatment, and she experienced minimal acute toxicities and no long-term toxicities. She developed recurrent PET-avid disease 23 months after Y-90 treatment, necessitating further local and continued systemic therapies. We report on the tumor control following Y-90 and EBRT treatment.
Collapse
Affiliation(s)
- Rushil Patel
- Renaissance School of Medicine, Stony Brook University, Stony Brook, NY, United States
| | - John Roberson
- Department of Radiation Oncology, Stony Brook University Hospital, Stony Brook, NY, United States
| | - Devina Prakash
- Division of Pediatric Hematology Oncology, Stony Brook Children’s Hospital, Stony Brook, NY, United States
| | - Rina Meyer
- Division of Pediatric Hematology Oncology, Stony Brook Children’s Hospital, Stony Brook, NY, United States
| | - Laura Hogan
- Division of Pediatric Hematology Oncology, Stony Brook Children’s Hospital, Stony Brook, NY, United States
| | - Christeen Azmy
- Division of Pediatric Hematology Oncology, Stony Brook Children’s Hospital, Stony Brook, NY, United States
| | - Valmore Suprenant
- Department of Radiology, Stony Brook University Hospital, Stony Brook, NY, United States
| | - Samuel Ryu
- Department of Radiation Oncology, Stony Brook University Hospital, Stony Brook, NY, United States
| | - Alexander Stessin
- Department of Radiation Oncology, Stony Brook University Hospital, Stony Brook, NY, United States
| |
Collapse
|
|
12
|
Abstract
External beam radiotherapy (EBRT) has improved efficacy and safety with advancements in technology and techniques. EBRT plays an important role in management of hepatocellular carcinoma (HCC). In resectable cases, EBRT serves as a bridge to transplantation or improves local control through adjuvant radiotherapy. In unresectable patients, EBRT offers high local control rates. In metastatic settings, EBRT provides effective palliation. This review presents an overview of radiotherapy treatment modalities used for HCC, current treatment guidelines for the role of EBRT in HCC, clinical outcomes between various EBRT approaches and other locoregional treatments for HCC, and the future role of EBRT for HCC.
Collapse
Affiliation(s)
- Chien Peter Chen
- Department of Radiation Oncology, Scripps Radiation Therapy Center, 10670 John Jay Hopkins Drive, San Diego, CA 92121, USA.
| |
Collapse
|
|
13
|
Malone CD, Gibby W, Tsai R, Kim SK, Lancia S, Akinwande O, Ramaswamy RS. Outcomes of Yttrium-90 Radioembolization for Unresectable Combined Biphenotypic Hepatocellular-Cholangiocarcinoma. J Vasc Interv Radiol 2020; 31:701-709. [PMID: 32127318 DOI: 10.1016/j.jvir.2019.09.028] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2019] [Revised: 09/24/2019] [Accepted: 09/26/2019] [Indexed: 02/06/2023] Open
Abstract
PURPOSE To evaluate outcomes of yttrium-90 radioembolization in patients with combined biphenotypic hepatocellular-cholangiocarcinoma (cHCC-CC). MATERIALS AND METHODS A retrospective review of patients with biopsy-confirmed cHCC-CC treated with yttrium-90 radioembolization between 2012 and 2018 was performed. Twenty-two patients with cHCC-CC (mean age 65.6 y, 17 men, 5 women) underwent 29 radioembolization treatments (5 resin, 24 glass microspheres). Survival data were available in 21 patients, and hepatic imaging response data were available in 20 patients. Hepatic imaging response to radioembolization was assessed on follow-up CT or MR imaging using modified Response Evaluation Criteria In Solid Tumours criteria. Univariate stepwise Cox regression analysis was used to evaluate the association between demographic and clinical factors and survival. Logistic regression evaluated associations between clinical factors and response to treatment, overall response, and disease control. RESULTS Hepatic imaging response was as follows: 15% complete response, 40% partial response, 10% stable disease, and 35% progressive disease (55% response rate, 65% disease control rate). Two patients were downstaged or bridged to transplant, and 1 patient was downstaged to resection. Median overall survival was 9.3 mo (range, 2.5-31.0 mo) from time of radioembolization. Nonreponse to treatment, bilobar disease, presence of multiple tumors, and elevated carbohydrate antigen 19-9 before treatment were associated with reduced survival after radioembolization. CONCLUSIONS Radioembolization is a viable option for locoregional control of cHCC-CC with good response and disease control rates.
Collapse
Affiliation(s)
- Christopher D Malone
- Mallinckrodt Institute of Radiology, Washington University School of Medicine in St. Louis, 510 South Kingshighway Boulevard, CB 8131, St. Louis, MO 63139
| | - Wendell Gibby
- Mallinckrodt Institute of Radiology, Washington University School of Medicine in St. Louis, 510 South Kingshighway Boulevard, CB 8131, St. Louis, MO 63139
| | - Richard Tsai
- Mallinckrodt Institute of Radiology, Washington University School of Medicine in St. Louis, 510 South Kingshighway Boulevard, CB 8131, St. Louis, MO 63139
| | - Seung Kwon Kim
- Mallinckrodt Institute of Radiology, Washington University School of Medicine in St. Louis, 510 South Kingshighway Boulevard, CB 8131, St. Louis, MO 63139
| | - Samantha Lancia
- Department of Biostatistics, Washington University in St. Louis, St. Louis, Missouri
| | - Olaguoke Akinwande
- Mallinckrodt Institute of Radiology, Washington University School of Medicine in St. Louis, 510 South Kingshighway Boulevard, CB 8131, St. Louis, MO 63139
| | - Raja S Ramaswamy
- Mallinckrodt Institute of Radiology, Washington University School of Medicine in St. Louis, 510 South Kingshighway Boulevard, CB 8131, St. Louis, MO 63139.
| |
Collapse
|
|
14
|
Carvalho VDO, Galastri FL, Affonso BB, Falsarella PM, Valle LGM, Ferraz-Neto BH, Rezende MBD, Motta-Leal-Filho JMD, Garcia RG, Nasser F. Transarterial radioembolization for liver tumors as neoadjuvant therapy: three case reports. EINSTEIN-SAO PAULO 2020; 18:eRC4990. [PMID: 32130329 PMCID: PMC7032884 DOI: 10.31744/einstein_journal/2020rc4990] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2019] [Accepted: 10/03/2019] [Indexed: 01/06/2023] Open
Abstract
Transarterial radioembolization (TARE) with yttrium-90 microspheres is a palliative locoregional treatment, minimally invasive for liver tumors. The neoadjuvant aim of this treatment is still controversial, however, selected cases with lesions initially considered unresectable have been enframed as candidates for curative therapy after hepatic transarterial radioembolization. We report three cases in which the hepatic transarterial radioembolization was used as neoadjuvant therapy in an effective way, allowing posterior potentially curative therapies.
Collapse
|
|
15
|
Köhler M, Harders F, Lohöfer F, Paprottka PM, Schaarschmidt BM, Theysohn J, Herrmann K, Heindel W, Schmidt HH, Pascher A, Stegger L, Rahbar K, Wildgruber M. Prognostic Factors for Overall Survival in Advanced Intrahepatic Cholangiocarcinoma Treated with Yttrium-90 Radioembolization. J Clin Med 2019; 9:jcm9010056. [PMID: 31881761 PMCID: PMC7020033 DOI: 10.3390/jcm9010056] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2019] [Revised: 12/16/2019] [Accepted: 12/23/2019] [Indexed: 02/06/2023] Open
Abstract
Purpose: To evaluate factors associated with survival following transarterial 90Y (yttrium) radioembolization (TARE) in patients with advanced intrahepatic cholangiocarcinoma (ICC). Methods: This retrospective multicenter study analyzed the outcome of three tertiary care cancer centers in patients with advanced ICC following resin microsphere TARE. Patients were included either after failed previous anticancer therapy, including relapse after surgical resection, or for having a minimum of 25% of total liver volume affected by ICC. Patients were stratified and response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria at 3 months. Kaplan–Meier analysis was performed to analyze survival followed by cox regression to determine independent prognostic factors for survival. Results: 46 patients were included (19 male, 27 female), median age 62.5 years (range 29–88 years). A total of 65% of patients had undergone previous therapy, while 63% had a tumor volume > 25% of the entire liver volume. Median survival was 9.5 months (95% CI: 6.1–12.9 months). Due to loss in follow-up, n = 37 patients were included in the survival analysis. Cox regression revealed the extent of liver disease to one or both liver lobes being associated with survival, irrespective of tumor volume (p = 0.041). Patients with previous surgical resection of ICC had significantly decreased survival (3.9 vs. 12.8 months, p = 0.002). No case of radiation-induced liver disease was observed. Discussion: Survival after 90Y TARE in patients with advanced ICC primarily depends on disease extent. Only limited prognostic factors are associated with a general poor overall survival.
Collapse
Affiliation(s)
- Michael Köhler
- Department of Clinical Radiology, Universitätsklinikum Münster, D-48149 Münster, Germany; (M.K.); (F.H.); (W.H.)
- Network Partner Site Westdeutsches Tumorzentrum, D-45147 Essen, Germany; (B.M.S.); (J.T.); (K.H.); (H.H.S.); (A.P.); (L.S.); (K.R.)
| | - Fabian Harders
- Department of Clinical Radiology, Universitätsklinikum Münster, D-48149 Münster, Germany; (M.K.); (F.H.); (W.H.)
| | - Fabian Lohöfer
- Division of Interventional Radiology, Klinikum rechts der Isar der Technischen Universität München, D-81675 München, Germany; (F.L.); (P.M.P.)
| | - Philipp M. Paprottka
- Division of Interventional Radiology, Klinikum rechts der Isar der Technischen Universität München, D-81675 München, Germany; (F.L.); (P.M.P.)
| | - Benedikt M. Schaarschmidt
- Network Partner Site Westdeutsches Tumorzentrum, D-45147 Essen, Germany; (B.M.S.); (J.T.); (K.H.); (H.H.S.); (A.P.); (L.S.); (K.R.)
- Department for Diagnostic and Interventional Radiology, Universitätsklinikum Essen, D-41547 Essen, Germany
| | - Jens Theysohn
- Network Partner Site Westdeutsches Tumorzentrum, D-45147 Essen, Germany; (B.M.S.); (J.T.); (K.H.); (H.H.S.); (A.P.); (L.S.); (K.R.)
- Department for Diagnostic and Interventional Radiology, Universitätsklinikum Essen, D-41547 Essen, Germany
| | - Ken Herrmann
- Network Partner Site Westdeutsches Tumorzentrum, D-45147 Essen, Germany; (B.M.S.); (J.T.); (K.H.); (H.H.S.); (A.P.); (L.S.); (K.R.)
- Department for Nuclear Medicine, Universitätsklinikum Essen, D-41547 Essen, Germany
| | - Walter Heindel
- Department of Clinical Radiology, Universitätsklinikum Münster, D-48149 Münster, Germany; (M.K.); (F.H.); (W.H.)
- Network Partner Site Westdeutsches Tumorzentrum, D-45147 Essen, Germany; (B.M.S.); (J.T.); (K.H.); (H.H.S.); (A.P.); (L.S.); (K.R.)
| | - Hartmut H. Schmidt
- Network Partner Site Westdeutsches Tumorzentrum, D-45147 Essen, Germany; (B.M.S.); (J.T.); (K.H.); (H.H.S.); (A.P.); (L.S.); (K.R.)
- Department of Gastroenterology and Hepatology, Universitätsklinikum Münster, D-48149 Münster, Germany
| | - Andreas Pascher
- Network Partner Site Westdeutsches Tumorzentrum, D-45147 Essen, Germany; (B.M.S.); (J.T.); (K.H.); (H.H.S.); (A.P.); (L.S.); (K.R.)
- Department for General, Visceral and Transplantation Surgery, Universitätsklinikum Münster, D-48149 Münster, Germany
| | - Lars Stegger
- Network Partner Site Westdeutsches Tumorzentrum, D-45147 Essen, Germany; (B.M.S.); (J.T.); (K.H.); (H.H.S.); (A.P.); (L.S.); (K.R.)
- Department of Nuclear Medicine, Universitätsklinikum Münster, D-48149 Münster, Germany
| | - Kambiz Rahbar
- Network Partner Site Westdeutsches Tumorzentrum, D-45147 Essen, Germany; (B.M.S.); (J.T.); (K.H.); (H.H.S.); (A.P.); (L.S.); (K.R.)
- Department of Nuclear Medicine, Universitätsklinikum Münster, D-48149 Münster, Germany
| | - Moritz Wildgruber
- Department of Clinical Radiology, Universitätsklinikum Münster, D-48149 Münster, Germany; (M.K.); (F.H.); (W.H.)
- Network Partner Site Westdeutsches Tumorzentrum, D-45147 Essen, Germany; (B.M.S.); (J.T.); (K.H.); (H.H.S.); (A.P.); (L.S.); (K.R.)
- Correspondence: ; Tel.: +49-251-83-56261
| |
Collapse
|
|
16
|
Underhill GH, Khetani SR. Emerging trends in modeling human liver disease in vitro. APL Bioeng 2019; 3:040902. [PMID: 31893256 PMCID: PMC6930139 DOI: 10.1063/1.5119090] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2019] [Accepted: 11/29/2019] [Indexed: 12/18/2022] Open
Abstract
The liver executes 500+ functions, such as protein synthesis, xenobiotic metabolism, bile production, and metabolism of carbohydrates/fats/proteins. Such functions can be severely degraded by drug-induced liver injury, nonalcoholic fatty liver disease, hepatitis B and viral infections, and hepatocellular carcinoma. These liver diseases, which represent a significant global health burden, are the subject of novel drug discovery by the pharmaceutical industry via the use of in vitro models of the human liver, given significant species-specific differences in disease profiles and drug outcomes. Isolated primary human hepatocytes (PHHs) are a physiologically relevant cell source to construct such models; however, these cells display a rapid decline in the phenotypic function within conventional 2-dimensional monocultures. To address such a limitation, several engineered platforms have been developed such as high-throughput cellular microarrays, micropatterned cocultures, self-assembled spheroids, bioprinted tissues, and perfusion devices; many of these platforms are being used to coculture PHHs with liver nonparenchymal cells to model complex cell cross talk in liver pathophysiology. In this perspective, we focus on the utility of representative platforms for mimicking key features of liver dysfunction in the context of chronic liver diseases and liver cancer. We further discuss pending issues that will need to be addressed in this field moving forward. Collectively, these in vitro liver disease models are being increasingly applied toward the development of new therapeutics that display an optimal balance of safety and efficacy, with a focus on expediting development, reducing high costs, and preventing harm to patients.
Collapse
Affiliation(s)
- Gregory H. Underhill
- Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA
| | - Salman R. Khetani
- Department of Bioengineering, University of Illinois at Chicago, Chicago, Illinois 60607, USA
| |
Collapse
|
|
17
|
Chen CP. Role of Radiotherapy in the Treatment of Hepatocellular Carcinoma. J Clin Transl Hepatol 2019; 7:183-190. [PMID: 31293919 PMCID: PMC6609847 DOI: 10.14218/jcth.2018.00060] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2018] [Revised: 04/27/2019] [Accepted: 05/08/2019] [Indexed: 02/06/2023] Open
Abstract
The role of radiotherapy in the treatment of hepatocellular carcinoma (HCC) has evolved over the past few decades with the advancement of technology and improved imaging. Radiotherapy can offer high local control rates in unresectable HCC, including cases with major vascular involvement, and can provide a modality to help bridge patients to potentially curative resection or transplantation. In metastatic cases, radiotherapy can provide good palliation. This review focuses on the common radiotherapy treatment modalities used for HCC, provides outcome comparisons of these radiotherapy techniques to outcomes with other treatment modalities for HCC, and highlights the discrepancy of the role of radiotherapy in HCC amongst the current available treatment guidelines.
Collapse
Affiliation(s)
- Chien Pong Chen
- Correspondence to: Chien Pong Chen, Department of Radiation Oncology, Scripps MD Anderson Cancer Center, 10670 John Jay Hopkins Drive, San Diego, CA 92121, USA. Tel: +1-858-554-4100, E-mail:
| |
Collapse
|
|
18
|
Choi C, Yoo GS, Cho WK, Park HC. Optimizing radiotherapy with immune checkpoint blockade in hepatocellular carcinoma. World J Gastroenterol 2019; 25:2416-2429. [PMID: 31171886 PMCID: PMC6543238 DOI: 10.3748/wjg.v25.i20.2416] [Citation(s) in RCA: 67] [Impact Index Per Article: 11.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2019] [Revised: 04/12/2019] [Accepted: 04/19/2019] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer, and its incidence is rapidly increasing in North America and Western Europe as well as South-East Asia. Patients with advanced stage HCC have very poor outcomes; therefore, the discovery of new innovative approaches is urgently needed. Cancer immunotherapy has become a game-changer and revolutionized cancer treatment. A comprehensive understanding of tumor-immune interactions led to the development of immune checkpoint inhibitors (ICIs) as new therapeutic tools, which have been used with great success. Targeting immune checkpoint molecules such as programmed cell death-1 (PD-1) and cytotoxic T lymphocyte-associated protein-4 (CTLA-4) reinvigorates anti-tumor immunity by restoring exhausted T cells. Despite their effectiveness in several types of cancer, of the many immune suppressive mechanisms limit the efficacy of ICI monotherapy. Radiation therapy (RT) is an essential local treatment modality for a broad range of malignancies, and it is currently gaining extensive attention as a promising combination partner with ICIs because of its ability to trigger immunogenic cell death. The efficacy of combination approaches using RT and ICIs has been well documented in numerous preclinical and clinical studies on various types of cancers but not HCC. The application of ICIs has now expanded to HCC, and RT is recognized as a promising modality in HCC. This review will highlight the current roles of PD-1 and CTLA-4 therapies and their combination with RT in the treatment of cancers, including HCC. In addition, this review will discuss the future perspectives of the combination of ICIs and RT in HCC treatment.
Collapse
Affiliation(s)
- Changhoon Choi
- Department of Radiation Oncology, Samsung Medical Center, Seoul 06351, South Korea
| | - Gyu Sang Yoo
- Department of Radiation Oncology, Samsung Medical Center, Seoul 06351, South Korea
| | - Won Kyung Cho
- Department of Radiation Oncology, Samsung Medical Center, Seoul 06351, South Korea
| | - Hee Chul Park
- Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, South Korea
| |
Collapse
|
|
19
|
Bakker RC, de Roos R, Ververs FFT, Lam MGEH, van der Lee MK, Zonnenberg BA, Krijger GC. Blood and urine analyses after radioembolization of liver malignancies with [ 166Ho]Ho-acetylacetonate-poly(l-lactic acid) microspheres. Nucl Med Biol 2019; 71:11-18. [PMID: 31108463 DOI: 10.1016/j.nucmedbio.2019.03.001] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2018] [Revised: 03/17/2019] [Accepted: 03/23/2019] [Indexed: 12/31/2022]
Abstract
BACKGROUND [166Ho]Ho-acetylacetonate-poly(L-lactic acid) microspheres were used in radioembolization of liver malignancies by intra-arterial administration. The primary aim of this study was to assess the stability and biodistribution of these microspheres. MATERIALS AND METHODS Peripheral blood and urine samples were obtained from two clinical studies. Patient and in vitro experiment samples were analyzed using inductively coupled plasma mass spectrometry (ICP-MS), gamma-ray spectroscopy, light microscopy, Coulter particle counting, and high performance liquid chromatography (HPLC). RESULTS The median percentage holmium compared to the total amount injected into the hepatic artery was 0.19% (range 0.08-2.8%) and 0.32% (range 0.03-1.8%) in the 1 h blood plasma and 24 h urine, respectively. Both the blood plasma and urine were correlated with the neutron irradiation exposure required for [166Ho]Ho-AcAc-PLLA microsphere production (ρ = 0.616, p = 0.002). After a temporary interruption of the phase 2 clinical study, the resuspension medium was replaced to precipitate [166Ho]Ho3+ pre-administration using phosphate. The in vitro near-maximum neutron irradiation experiments showed significant [166Ho]Ho-AcAc-PLLA microsphere damage. CONCLUSION The amount of holmium in the peripheral blood and urine samples after [166Ho]Ho-AcAc-PLLA microsphere intrahepatic infusion was low. A further decrease was observed after reformulation of the resuspension solution but minimization of production damage is necessary.
Collapse
Affiliation(s)
- Robbert C Bakker
- Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, the Netherlands
| | - Remmert de Roos
- Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, the Netherlands
| | - F F Tessa Ververs
- Department of Pharmacy, University Medical Center Utrecht, the Netherlands
| | - Marnix G E H Lam
- Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, the Netherlands
| | | | - Bernard A Zonnenberg
- Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, the Netherlands
| | - Gerard C Krijger
- Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, the Netherlands.
| |
Collapse
|
|
20
|
Limeres MJ, Moretton MA, Bernabeu E, Chiappetta DA, Cuestas ML. Thinking small, doing big: Current success and future trends in drug delivery systems for improving cancer therapy with special focus on liver cancer. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2019; 95:328-341. [DOI: 10.1016/j.msec.2018.11.001] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/03/2018] [Revised: 09/20/2018] [Accepted: 11/01/2018] [Indexed: 01/19/2023]
|
|
21
|
Mallia MB, Chirayil V, Dash A. Improved freeze-dried kit for the preparation of 188ReN-DEDC/lipiodol for the therapy of unresectable hepatocellular carcinoma. Appl Radiat Isot 2018; 137:147-153. [PMID: 29625347 DOI: 10.1016/j.apradiso.2018.03.018] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2017] [Accepted: 03/24/2018] [Indexed: 02/02/2023]
Abstract
Rhenium-188-N-(DEDC)2/lipiodol (abbreviated as 188ReN-DEDC, where DEDC = monoanionic diethyldithiocarbamate) is a clinically proven radiopharmaceutical for the therapy of unresectable hepatocellular carcinoma (HCC) through trans arterial radioembolization (TARE). A two-vial freeze-dried kit for the preparation of [188ReN(DEDC)2] complex using sodium perrhenate (Na188ReO4) obtained from a commercial Tungsten-188/Rhenium-188 generator had been reported earlier. This method required addition of stipulated volume of glacial acetic acid into vial 1 by the user for efficient preparation of [188ReN]2+ intermediate. An error in this step can result in low radiochemical yield of [188ReN]2+ intermediate as well as sub-optimal pH of the reaction mixture for the second step, leading to poor radiochemical purity of 188ReN-DEDC complex. In the present work, a solution to this problem was found by including an oxalate buffer of pH = 3 in vial 1, eliminating the need for the addition of glacial acetic acid by the user. This modification not only made the kits more user-friendly, it resulted in significant improvement in the kinetics of formation of [188ReN]2+ intermediate, wherein > 95% radiochemical purity could be achieved within 5 min incubation at ambient temperature. Moreover, the novel route for the preparation of [188ReN]2+ intermediate may be applied to any radiopharmaceutical based on 188ReN-core.
Collapse
Affiliation(s)
- Madhava B Mallia
- Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Mumbai 400085, India; Homi Bhabha National Institute, Anushakti Nagar, Mumbai 400094, India.
| | - Viju Chirayil
- Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Mumbai 400085, India
| | - Ashutosh Dash
- Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Mumbai 400085, India
| |
Collapse
|
|
22
|
Justinger C, Gruden J, Kouladouros K, Stravodimos C, Reimer P, Tannapfel A, Binnenhei M, Bentz M, Tatsch K, Rüdiger T, Schön MR. Histopathological changes resulting from selective internal radiotherapy (SIRT). J Surg Oncol 2018; 117:1084-1091. [DOI: 10.1002/jso.24967] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2017] [Accepted: 12/10/2017] [Indexed: 12/12/2022]
Affiliation(s)
- Christoph Justinger
- Department of General and Visceral Surgery; Klinikum Karlsruhe; Karlsruhe Germany
| | - Juliana Gruden
- Institute of Pathology; Klinikum Karlsruhe; Karlsruhe Germany
| | | | - Christos Stravodimos
- Department of General and Visceral Surgery; Klinikum Karlsruhe; Karlsruhe Germany
| | - Peter Reimer
- Institute of Diagnostic and Interventional Radiology; Klinikum Karlsruhe; Karlsruhe Germany
| | | | | | - Martin Bentz
- Department of Oncology; Klinikum Karlsruhe; Karlsruhe Germany
| | - Klaus Tatsch
- Department of Nuclear Medicine; Klinikum Karlsruhe; Karlsruhe Germany
| | - Thomas Rüdiger
- Institute of Pathology; Klinikum Karlsruhe; Karlsruhe Germany
| | - Michael R. Schön
- Department of General and Visceral Surgery; Klinikum Karlsruhe; Karlsruhe Germany
| |
Collapse
|