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Sharma R, Yadav J, Bhat SA, Musayev A, Myrzagulova S, Sharma D, Padha N, Saini M, Tuli HS, Singh T. Emerging Trends in Neuroblastoma Diagnosis, Therapeutics, and Research. Mol Neurobiol 2025; 62:6423-6466. [PMID: 39804528 DOI: 10.1007/s12035-024-04680-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2024] [Accepted: 12/20/2024] [Indexed: 03/29/2025]
Abstract
This review explores the current understanding and recent advancements in neuroblastoma, one of the most common extracranial solid pediatric cancers, accounting for ~ 15% of childhood cancer-related mortality. The hallmarks of NBL, including angiogenesis, metastasis, apoptosis resistance, cell cycle dysregulation, drug resistance, and responses to hypoxia and ROS, underscore its complex biology. The tumor microenvironment's significance in disease progression is acknowledged in this study, along with the pivotal role of cancer stem cells in sustaining tumor growth and heterogeneity. A number of molecular signatures are being studied in order to better understand the disease, with many of them serving as targets for the development of new therapeutics. This includes inhibitor therapies for NBL patients, which notably concentrate on ALK signaling, MDM2, PI3K/Akt/mTOR, Wnt, and RAS-MAPK pathways, along with regulators of epigenetic mechanisms. Additionally, this study offers an extensive understanding of the molecular therapies used, such as monoclonal antibodies and CAR-T therapy, focused on both preclinical and clinical studies. Radiation therapy's evolving role and the promise of stem cell transplantation-mediated interventions underscore the dynamic landscape of NBL treatment. This study has also emphasized the recent progress in the field of diagnosis, encompassing the adoption of artificial intelligence and liquid biopsy as a non-intrusive approach for early detection and ongoing monitoring of NBL. Furthermore, the integration of innovative treatment approaches such as CRISPR-Cas9, and cancer stem cell therapy has also been emphasized in this review.
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Affiliation(s)
- Rishabh Sharma
- Translational Oncology Laboratory, Department of Zoology, Hansraj College, Delhi University, New Delhi, 110007, India
- Amity Stem Cell Institute, Amity Medical School, Amity University, Haryana, 122412, India
| | - Jaya Yadav
- Translational Oncology Laboratory, Department of Zoology, Hansraj College, Delhi University, New Delhi, 110007, India
- Amity Stem Cell Institute, Amity Medical School, Amity University, Haryana, 122412, India
| | - Sajad Ahmad Bhat
- Asfendiyarov Kazakh National Medical University, Almaty, 050000, Kazakhstan
- Department of Biochemistry, NIMS University, Rajasthan, Jaipur, 303121, India
| | - Abdugani Musayev
- Asfendiyarov Kazakh National Medical University, Almaty, 050000, Kazakhstan
| | | | - Deepika Sharma
- Translational Oncology Laboratory, Department of Zoology, Hansraj College, Delhi University, New Delhi, 110007, India
| | - Nipun Padha
- Translational Oncology Laboratory, Department of Zoology, Hansraj College, Delhi University, New Delhi, 110007, India
- Department of Zoology, Cluster University of Jammu, Jammu, 180001, India
| | - Manju Saini
- Translational Oncology Laboratory, Department of Zoology, Hansraj College, Delhi University, New Delhi, 110007, India
- Amity Stem Cell Institute, Amity Medical School, Amity University, Haryana, 122412, India
| | - Hardeep Singh Tuli
- Department of Bio-Sciences and Technology, Maharishi Markandeshwar (Deemed to Be University), Mullana, Ambala, Haryana, 133207, India
| | - Tejveer Singh
- Translational Oncology Laboratory, Department of Zoology, Hansraj College, Delhi University, New Delhi, 110007, India.
- Division of Cyclotron and Radiopharmaceutical Sciences, Institute of Nuclear Medicine and Allied Sciences, (INMAS-DRDO), New Delhi, Delhi, 110054, India.
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Gazsi I, Marcu LG. A Systematic Review of SBRT Boost for Cervical Cancer Patients Who Cannot Benefit from Brachytherapy. Curr Oncol 2025; 32:170. [PMID: 40136374 PMCID: PMC11941556 DOI: 10.3390/curroncol32030170] [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: 03/04/2025] [Revised: 03/13/2025] [Accepted: 03/14/2025] [Indexed: 03/27/2025] Open
Abstract
Stereotactic body radiation therapy has emerged as a promising alternative to brachytherapy, delivering high doses to tumors with precision while sparing surrounding organs. This systematic review evaluates the role of SBRT as a boost for patients who are ineligible for brachytherapy. A total of 17 studies, involving 288 patients, were analyzed, focusing on dosimetric parameters and toxicity. The radiation regimens varied in dose and fractionation schedules, with external beam doses ranging from 44 to 61.6 Gy, and SBRT boost doses ranging from 5 to 30 Gy. The total EQD2 doses were between 50.5 and 92.4 Gy. The results indicate adequate tumor control with SBRT, with local control rates ranging from 57% to 95.5%. The acute genitourinary and gastrointestinal toxicities were mostly grade 1 or 2, while late toxicities were less common. The overall survival rates varied between 34% and 96%. These results suggest that SBRT boost offers a viable option for cervical cancer patients ineligible for brachytherapy, with acceptable toxicity and promising survival outcomes. Nevertheless, the scarcity of data, which mainly originate from small studies with patients having varied stages of disease, as well as the lack of long-term follow up with SBRT, should encourage clinicians to utilize brachytherapy whenever suitable as a boost in these patient cohorts.
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Affiliation(s)
- Iozsef Gazsi
- Faculty of Physics, West University of Timisoara, 300223 Timisoara, Romania;
- County Emergency Clinical Hospital, 410469 Oradea, Romania
| | - Loredana G. Marcu
- Faculty of Informatics & Science, University of Oradea, 410087 Oradea, Romania
- Allied Health & Human Performance, University of South Australia, Adelaide 5000, Australia
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Xu C, Qin X, Wei X, Yu J, Zhang Y, Zhang Y, Ding D, Song J, Pu K. A cascade X-ray energy converting approach toward radio-afterglow cancer theranostics. NATURE NANOTECHNOLOGY 2025; 20:286-295. [PMID: 39548317 DOI: 10.1038/s41565-024-01809-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/03/2024] [Accepted: 09/18/2024] [Indexed: 11/17/2024]
Abstract
Leveraging X-rays to initiate prolonged luminescence (radio-afterglow) and stimulate radiodynamic 1O2 production from optical agents provides opportunities for diagnosis and therapy at tissue depths inaccessible to light. However, X-ray-responsive organic luminescent materials are rare due to their intrinsic low X-ray conversion efficiency. Here we report a cascade X-ray energy converting approach to develop organic radio-afterglow nanoprobes (RANPs) for cancer theranostics. RANPs comprise a radiowave absorber that down-converts X-ray energy to emit radioluminescence, which is transferred to a radiosensitizer to produce singlet oxygen (1O2). 1O2 then reacts with a radio-afterglow substrate to generate an active intermediate that simultaneously decomposes to emit radio-afterglow. Through finetuning such a cascade, intraparticle radioluminescence energy transfer and the 1O2 transfer process, RANPs possess tunable wavelengths and long half-lives, and generate radio-afterglow and 1O2 at tissue depths of up to 15 cm. Moreover, we developed a biomarker-activatable nanoprobe (tRANP) that produces a tumour-specific radio-afterglow signal, leading to ultrasensitive detection and the possibility of surgical removal of diminutive tumours (1 mm3) under an X-ray dosage 20 times lower than inorganic materials. The efficient radiodynamic 1O2 generation of tRANP permits complete tumour eradication at an X-ray dosage lower than clinical radiotherapy and a drug dosage one to two orders of magnitude lower than most existing inorganic agents, leading to prolonged survival rates with minimized radiation-related adverse effects. Thus, our work reveals a generic approach to address the lack of organic radiotheranostic materials and provides molecular design towards precision cancer radiotherapy.
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Affiliation(s)
- Cheng Xu
- School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, Singapore, Singapore
| | - Xue Qin
- State Key Laboratory of Chemical Resource Engineering, College of Chemistry, Beijing University of Chemical Technology, Beijing, PR China
| | - Xin Wei
- School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, Singapore, Singapore
| | - Jie Yu
- National Engineering Research Centre for Nanomedicine, College of Life Science and Technology, Hubei Key Laboratory of Bio-inorganic Chemistry and Materia Medical, Huazhong University of Science and Technology, Wuhan, PR China
| | - Youjia Zhang
- Department of Nuclear Medicine, China-Japan Union Hospital of Jilin University, Changchun, Jilin, PR China
| | - Yan Zhang
- National Engineering Research Centre for Nanomedicine, College of Life Science and Technology, Hubei Key Laboratory of Bio-inorganic Chemistry and Materia Medical, Huazhong University of Science and Technology, Wuhan, PR China.
| | - Dan Ding
- Frontiers Science Center for New Organic Matter, Engineering & Smart Sensing Interdisciplinary Science Center, MOE Key Laboratory of Bioactive Materials, and College of Life Sciences, Nankai University, Tianjin, PR China.
| | - Jibin Song
- State Key Laboratory of Chemical Resource Engineering, College of Chemistry, Beijing University of Chemical Technology, Beijing, PR China.
| | - Kanyi Pu
- School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, Singapore, Singapore.
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore.
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Organic radio-afterglow nanoprobes for cancer theranostics. NATURE NANOTECHNOLOGY 2025; 20:194-195. [PMID: 39548318 DOI: 10.1038/s41565-024-01810-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/17/2024]
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Vorbach SM, Seppi T, Sarcletti MP, Kollotzek S, Mangesius J, Lehmann J, Riedl D, Pointner MJ, Santer M, Dejaco D, Nevinny‐Stickel M, Ganswindt U. A novel prognostic score (HAMP) for head and neck cancer patients with single and multiple SBRT-treated lung metastases derived from retrospective analyses of survival outcome. Head Neck 2025; 47:242-253. [PMID: 39114975 PMCID: PMC11635751 DOI: 10.1002/hed.27913] [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: 02/28/2024] [Revised: 07/26/2024] [Accepted: 07/26/2024] [Indexed: 12/13/2024] Open
Abstract
BACKGROUND We report on the characterization and introduction of a novel prognostic score for patients undergoing stereotactic body radiotherapy (SBRT) for the treatment of single and multiple pulmonary metastases (PMs) derived from head and neck cancer (HNC). METHODS In this retrospective study, we examined selected factors associated with progression-free survival (PFS) and overall survival (OS) among 59 patients with HNC treated with SBRT for a total of 118 PMs, between 2009 and 2023. Factors related to survival were included in the prognostic scoring system. RESULTS Prognostic factors including histology, age, number of metastases, and performance status at first SBRT were weighted differently depending on the strength of correlation to PFS and OS. Total prognostic scores (HAMP) ranged from 13 to 24 points, with a cut-off total score of ≤18 scoring points for patients in a high-risk (HR) subcohort, and of ≥19 scoring points for patients in a low-risk group (LR). Median PFS (23.8 vs. 5.5 months, p < 0.001) and OS (61.3 vs. 16.4 months, p < 0.001) were significantly longer in the low-risk group compared to the high-risk group. CONCLUSION The HAMP score might be a convenient tool to facilitate individualized treatment decisions and appropriate follow-up. The accuracy and reliability of the score requires further evaluation in prospective studies.
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Affiliation(s)
- Samuel M. Vorbach
- Department of Radiation OncologyMedical University of InnsbruckInnsbruckAustria
| | - Thomas Seppi
- Department of Radiation OncologyMedical University of InnsbruckInnsbruckAustria
| | - Manuel P. Sarcletti
- Department of Radiation OncologyMedical University of InnsbruckInnsbruckAustria
| | - Siegfried Kollotzek
- Department of Radiation OncologyMedical University of InnsbruckInnsbruckAustria
| | - Julian Mangesius
- Department of Radiation OncologyMedical University of InnsbruckInnsbruckAustria
| | - Jens Lehmann
- Department of Psychiatry, Psychotherapy, Psychosomatics and Medical PsychologyUniversity Hospital of Psychiatry II, Medical University of InnsbruckInnsbruckAustria
| | - David Riedl
- Department of Psychiatry, Psychotherapy, Psychosomatics and Medical PsychologyUniversity Hospital of Psychiatry II, Medical University of InnsbruckInnsbruckAustria
| | - Martin J. Pointner
- Department of Radiation OncologyMedical University of InnsbruckInnsbruckAustria
| | - Matthias Santer
- Department of Otorhinolaryngology – Head and Neck SurgeryMedical University of InnsbruckInnsbruckAustria
| | - Daniel Dejaco
- Department of Otorhinolaryngology – Head and Neck SurgeryMedical University of InnsbruckInnsbruckAustria
| | | | - Ute Ganswindt
- Department of Radiation OncologyMedical University of InnsbruckInnsbruckAustria
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Botti A, Finocchiaro D, Panico N, Trojani V, Paolani G, Iori F, Sghedoni R, Cagni E, Lambertini D, Ciammella P, Iotti C, Iori M. LatticeOpt: An automatic tool for planning optimisation of spatially fractionated stereotactic body radiotherapy. Phys Med 2024; 126:104823. [PMID: 39332099 DOI: 10.1016/j.ejmp.2024.104823] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2024] [Revised: 09/05/2024] [Accepted: 09/22/2024] [Indexed: 09/29/2024] Open
Abstract
PURPOSE Lattice radiotherapy (LRT) is a three dimensional (3D) implementation of spatially fractionated radiation therapy, based on regular spatial distribution of high dose spheres (vertices) inside the target. Due to tumour shape heterogeneity, finding the best lattice arrangement is not trivial. The aim of this study was to develop the LatticeOpt tool to generate the best lattice structures on clinical cases for treatment planning. METHODS Developed in MATLAB, LatticeOpt finds the 3D-spatial configurations that maximize the number of vertices within the gross target volume (GTV). If organs at risk (OARs) are considered, it chooses the solution that minimizes the overlapping volume histograms (OVH). Otherwise, the lattice structure with the minimum Hausdorff distance between vertices and GTV boundary is chosen to avoid unpopulated regions. Different lattice structures were created for 20 patients, with (OVHopt) and without (OVHunopt) OVH minimization. Imported into TPS (Eclipse, Varian), corresponding plans were generated and evaluated in terms of OAR mean and maximum doses, GTV vertex coverage and dose gradients, as well as pre-clinical plan dosimetry. RESULTS Plans based on an optimized lattice structure (OVHopt, OVHunopt) had similar dose distributions in terms of vertex coverage and gradient index score. OAR sparing was observed in all patients, with a 4 % and 9 % difference for mean and max dose (both p-values <0.01), respectively. The best vertices dimensions and their relative distances were patient dependent. CONCLUSIONS LatticeOpt was able to reduce the time-consuming procedures of LRT, as well as to achieve standardized and reproducible results, useful for multicentre studies.
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Affiliation(s)
- Andrea Botti
- Azienda USL-IRCCS di Reggio Emilia, Medical Physics Unit, Department of Advanced Technology, Reggio Emilia, Italy.
| | - Domenico Finocchiaro
- Azienda Ospedaliero-Universitaria di Modena, Medical Physics Unit, Modena, Italy
| | - Nicola Panico
- Azienda USL-IRCCS di Reggio Emilia, Medical Physics Unit, Department of Advanced Technology, Reggio Emilia, Italy
| | - Valeria Trojani
- Azienda USL-IRCCS di Reggio Emilia, Medical Physics Unit, Department of Advanced Technology, Reggio Emilia, Italy
| | - Giulia Paolani
- Azienda USL-IRCCS di Reggio Emilia, Medical Physics Unit, Department of Advanced Technology, Reggio Emilia, Italy
| | - Federico Iori
- Azienda USL-IRCCS di Reggio Emilia, Radiotherapy Unit, Department of Advanced Technology, Reggio Emilia, Italy
| | - Roberto Sghedoni
- Azienda USL-IRCCS di Reggio Emilia, Medical Physics Unit, Department of Advanced Technology, Reggio Emilia, Italy
| | - Elisabetta Cagni
- Azienda USL-IRCCS di Reggio Emilia, Medical Physics Unit, Department of Advanced Technology, Reggio Emilia, Italy
| | - Daniele Lambertini
- Azienda USL-IRCCS di Reggio Emilia, Medical Physics Unit, Department of Advanced Technology, Reggio Emilia, Italy
| | - Patrizia Ciammella
- Azienda USL-IRCCS di Reggio Emilia, Radiotherapy Unit, Department of Advanced Technology, Reggio Emilia, Italy
| | - Cinzia Iotti
- Azienda USL-IRCCS di Reggio Emilia, Medical Physics Unit, Department of Advanced Technology, Reggio Emilia, Italy
| | - Mauro Iori
- Azienda USL-IRCCS di Reggio Emilia, Medical Physics Unit, Department of Advanced Technology, Reggio Emilia, Italy
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Pandey P, Chaudhary R, Tripathi D, Lavudi K, Dua K, Weinfeld M, Lavasanifar A, Rajinikanth PS. Personalized treatment approach for HER2-positive metastatic breast cancer. Med Oncol 2024; 41:252. [PMID: 39320608 DOI: 10.1007/s12032-024-02504-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2024] [Accepted: 09/13/2024] [Indexed: 09/26/2024]
Abstract
Breast cancer (BC) is a leading global concern for women, with 30% being HER2-positive cases linked to poorer outcomes. Targeted therapies like trastuzumab deruxtecan (T-DXd), trastuzumab, pertuzumab, and T-DM1 have revolutionized HER2-positive metastatic breast cancer (MBC) treatment. Although these therapies have improved MBC management and patient outcomes, resistance can develop, reducing effectiveness. Personalized strategies based on tumor characteristics offer hope for better responses and longer outcomes. This review outlines insights into MBC patients responding well to anti-HER2 treatments, even across multiple treatment regimen. Recent immunotherapy, locoregional therapy, and liquid biopsy breakthroughs are covered, suggesting ways to increase long-term responders. Personalized approaches have boosted HER2-positive MBC outcomes, and ongoing research is crucial to uncover new treatments and biomarkers, potentially elevating long-term response rates and prognoses. This may aid in providing new direction to breast cancer clinics.
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Affiliation(s)
- Prashant Pandey
- Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB, T6G 2H7, Canada
- Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University, Lucknow, Uttar Pradesh, 226025, India
| | - Rishabh Chaudhary
- Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University, Lucknow, Uttar Pradesh, 226025, India
| | - Devika Tripathi
- PSIT-Pranveer Singh Institute of Technology (Pharmacy), Kanpur, India
| | - Kousalya Lavudi
- Department of Radiation Oncology, College of Medicine, The Ohio State University, Columbus, OH, 43210, USA
- Comprehensive Cancer Center, The Ohio State University, Columbus, OH, 43210, USA
| | - Kamal Dua
- Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Sydney, NSW, 2007, Australia
| | - Michael Weinfeld
- Cross Cancer Institute and Department of Oncology, University of Alberta, Edmonton, AB, T6G 1Z2, Canada
| | - Afsaneh Lavasanifar
- Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB, T6G 2H7, Canada
- Department of Chemical and Material Engineering, University of Alberta, Edmonton, AB, T6G 2V4, Canada
| | - P S Rajinikanth
- Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University, Lucknow, Uttar Pradesh, 226025, India.
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Fadlallah H, El Masri J, Fakhereddine H, Youssef J, Chemaly C, Doughan S, Abou-Kheir W. Colorectal cancer: Recent advances in management and treatment. World J Clin Oncol 2024; 15:1136-1156. [PMID: 39351451 PMCID: PMC11438855 DOI: 10.5306/wjco.v15.i9.1136] [Citation(s) in RCA: 9] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2023] [Revised: 06/11/2024] [Accepted: 07/29/2024] [Indexed: 08/29/2024] Open
Abstract
Colorectal cancer (CRC) is the third most common cancer worldwide, and the second most common cause of cancer-related death. In 2020, the estimated number of deaths due to CRC was approximately 930000, accounting for 10% of all cancer deaths worldwide. Accordingly, there is a vast amount of ongoing research aiming to find new and improved treatment modalities for CRC that can potentially increase survival and decrease overall morbidity and mortality. Current management strategies for CRC include surgical procedures for resectable cases, and radiotherapy, chemotherapy, and immunotherapy, in addition to their combination, for non-resectable tumors. Despite these options, CRC remains incurable in 50% of cases. Nonetheless, significant improvements in research techniques have allowed for treatment approaches for CRC to be frequently updated, leading to the availability of new drugs and therapeutic strategies. This review summarizes the most recent therapeutic approaches for CRC, with special emphasis on new strategies that are currently being studied and have great potential to improve the prognosis and lifespan of patients with CRC.
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Affiliation(s)
- Hiba Fadlallah
- Department of Anatomy, Cell Biology and Physiological Sciences, American University of Beirut, Beirut 1107-2020, Lebanon
| | - Jad El Masri
- Department of Anatomy, Cell Biology and Physiological Sciences, American University of Beirut, Beirut 1107-2020, Lebanon
| | - Hiam Fakhereddine
- Department of Anatomy, Cell Biology and Physiological Sciences, American University of Beirut, Beirut 1107-2020, Lebanon
| | - Joe Youssef
- Department of Anatomy, Cell Biology and Physiological Sciences, American University of Beirut, Beirut 1107-2020, Lebanon
| | - Chrystelle Chemaly
- Department of Anatomy, Cell Biology and Physiological Sciences, American University of Beirut, Beirut 1107-2020, Lebanon
| | - Samer Doughan
- Department of Surgery, American University of Beirut Medical Center, Beirut 1107-2020, Lebanon
| | - Wassim Abou-Kheir
- Department of Anatomy, Cell Biology and Physiological Sciences, American University of Beirut, Beirut 1107-2020, Lebanon
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Kulkarni SE, Patel SA, Sun Y, Jani AB, Gillespie TW, McDonald MW, Liu Y. Secondary Cancer in Prostate Cancer Patients Treated With Advanced External Beam Radiation Therapy. Int J Part Ther 2024; 13:100627. [PMID: 39296493 PMCID: PMC11409042 DOI: 10.1016/j.ijpt.2024.100627] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2024] [Revised: 08/11/2024] [Accepted: 08/15/2024] [Indexed: 09/21/2024] Open
Abstract
Purpose Previous studies have shown that external beam radiation therapy is associated with an increased risk of second primary cancer (SPC) among prostate cancer (PCa) patients, but the relative risks associated with newer and advanced radiation modalities such as proton beam therapy (PBT) and stereotactic body radiation therapy (SBRT) are unclear. This study aimed to assess the relative probability of SPC among patients treated with these newer modalities compared to intensity-modulated radiation therapy (IMRT). Patients and Methods Using the National Cancer Database (NCDB), N0M0 PCa cases diagnosed between 2004 and 2018 were identified. Second primary cancer probabilities were compared among those treated with curative-intent PBT, SBRT, and IMRT. Multivariable logistic regression and inverse probability of treatment weighting were used to generate adjusted odds ratios (aORs) and 95% confidence intervals (CIs). Results In total, 133 898 patients were included, with a median age of 69 years and median follow-up of 6.4 years. As their first course of treatment, 3420 (2.6%) received PBT, 121 211 (90.5%) received IMRT, and 9267 (6.9%) received SBRT. Compared with IMRT, PBT and SBRT were associated with lower SPC risk (aORs and 95% CIs, PBT: 0.49 [0.40-0.60], SBRT: 0.57 (0.51-0.63), P < .001). Inverse probability of treatment weighting analyses corroborated these results. Conclusion In this large national cohort, PBT and SBRT performed similarly and were associated with reduced SPC risk compared to IMRT when used as the first course of treatment.
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Affiliation(s)
- Sarah E Kulkarni
- Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, Georgia, USA
| | - Sagar A Patel
- Department of Radiation Oncology, Emory University School of Medicine, Atlanta, Georgia, USA
| | - Yuxian Sun
- Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, Georgia, USA
| | - Ashesh B Jani
- Department of Radiation Oncology, Emory University School of Medicine, Atlanta, Georgia, USA
| | - Theresa W Gillespie
- Department of Surgery, Emory University School of Medicine, Atlanta, Georgia, USA
| | - Mark W McDonald
- Department of Radiation Oncology, Emory University School of Medicine, Atlanta, Georgia, USA
| | - Yuan Liu
- Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, Georgia, USA
- Biostatistics and Bioinformatics Shared Resource, Winship Cancer Institute, Emory University, Atlanta, Georgia, USA
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Li C, Guo Y, Lin X, Feng X, Xu D, Yang R. Deep reinforcement learning in radiation therapy planning optimization: A comprehensive review. Phys Med 2024; 125:104498. [PMID: 39163802 DOI: 10.1016/j.ejmp.2024.104498] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2024] [Revised: 07/08/2024] [Accepted: 08/06/2024] [Indexed: 08/22/2024] Open
Abstract
PURPOSE The formulation and optimization of radiation therapy plans are complex and time-consuming processes that heavily rely on the expertise of medical physicists. Consequently, there is an urgent need for automated optimization methods. Recent advancements in reinforcement learning, particularly deep reinforcement learning (DRL), show great promise for automating radiotherapy planning. This review summarizes the current state of DRL applications in this field, evaluates their effectiveness, and identifies challenges and future directions. METHODS A systematic search was conducted in Google Scholar, PubMed, IEEE Xplore, and Scopus using keywords such as "deep reinforcement learning", "radiation therapy", and "treatment planning". The extracted data were synthesized for an overview and critical analysis. RESULTS The application of deep reinforcement learning in radiation therapy plan optimization can generally be divided into three categories: optimizing treatment planning parameters, directly optimizing machine parameters, and adaptive radiotherapy. From the perspective of disease sites, DRL has been applied to cervical cancer, prostate cancer, vestibular schwannoma, and lung cancer. Regarding types of radiation therapy, it has been used in HDRBT, IMRT, SBRT, VMAT, GK, and Cyberknife. CONCLUSIONS Deep reinforcement learning technology has played a significant role in advancing the automated optimization of radiation therapy plans. However, there is still a considerable gap before it can be widely applied in clinical settings due to three main reasons: inefficiency, limited methods for quality assessment, and poor interpretability. To address these challenges, significant research opportunities exist in the future, such as constructing evaluators, parallelized training, and exploring continuous action spaces.
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Affiliation(s)
- Can Li
- Institute of Operations Research and Information Engineering, Beijing University of Technology, Beijing 100124, PR China
| | - Yuqi Guo
- Institute of Operations Research and Information Engineering, Beijing University of Technology, Beijing 100124, PR China
| | - Xinyan Lin
- Department of Radiation Oncology, Cancer Center, Peking University Third Hospital, Beijing, 100191, China; School of Physics, Beihang University, Beijing, 102206, China
| | - Xuezhen Feng
- Department of Radiation Oncology, Cancer Center, Peking University Third Hospital, Beijing, 100191, China; School of Nuclear Science and Technology, University of South China, Hengyang, 421001, China
| | - Dachuan Xu
- Institute of Operations Research and Information Engineering, Beijing University of Technology, Beijing 100124, PR China.
| | - Ruijie Yang
- Department of Radiation Oncology, Cancer Center, Peking University Third Hospital, Beijing, 100191, China.
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Winter RC, Amghar M, Wacker AS, Bakos G, Taş H, Roscher M, Kelly JM, Benešová-Schäfer M. Future Treatment Strategies for Cancer Patients Combining Targeted Alpha Therapy with Pillars of Cancer Treatment: External Beam Radiation Therapy, Checkpoint Inhibition Immunotherapy, Cytostatic Chemotherapy, and Brachytherapy. Pharmaceuticals (Basel) 2024; 17:1031. [PMID: 39204136 PMCID: PMC11359268 DOI: 10.3390/ph17081031] [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: 06/12/2024] [Revised: 07/22/2024] [Accepted: 07/25/2024] [Indexed: 09/03/2024] Open
Abstract
Cancer is one of the most complex and challenging human diseases, with rising incidences and cancer-related deaths despite improved diagnosis and personalized treatment options. Targeted alpha therapy (TαT) offers an exciting strategy emerging for cancer treatment which has proven effective even in patients with advanced metastatic disease that has become resistant to other treatments. Yet, in many cases, more sophisticated strategies are needed to stall disease progression and overcome resistance to TαT. The combination of two or more therapies which have historically been used as stand-alone treatments is an approach that has been pursued in recent years. This review aims to provide an overview on TαT and the four main pillars of therapeutic strategies in cancer management, namely external beam radiation therapy (EBRT), immunotherapy with checkpoint inhibitors (ICI), cytostatic chemotherapy (CCT), and brachytherapy (BT), and to discuss their potential use in combination with TαT. A brief description of each therapy is followed by a review of known biological aspects and state-of-the-art treatment practices. The emphasis, however, is given to the motivation for combination with TαT as well as the pre-clinical and clinical studies conducted to date.
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Affiliation(s)
- Ruth Christine Winter
- Research Group Molecular Biology of Systemic Radiotherapy/Translational Radiotheranostics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany; (R.C.W.); (M.A.); (G.B.); (H.T.)
| | - Mariam Amghar
- Research Group Molecular Biology of Systemic Radiotherapy/Translational Radiotheranostics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany; (R.C.W.); (M.A.); (G.B.); (H.T.)
| | - Anja S. Wacker
- Department of Radiology, Molecular Imaging Innovations Institute (MI3), Weill Cornell Medicine, 413 East 69th Street, New York, NY 10021, USA; (A.S.W.); (J.M.K.)
| | - Gábor Bakos
- Research Group Molecular Biology of Systemic Radiotherapy/Translational Radiotheranostics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany; (R.C.W.); (M.A.); (G.B.); (H.T.)
| | - Harun Taş
- Research Group Molecular Biology of Systemic Radiotherapy/Translational Radiotheranostics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany; (R.C.W.); (M.A.); (G.B.); (H.T.)
| | - Mareike Roscher
- Service Unit for Radiopharmaceuticals and Preclinical Studies, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany;
| | - James M. Kelly
- Department of Radiology, Molecular Imaging Innovations Institute (MI3), Weill Cornell Medicine, 413 East 69th Street, New York, NY 10021, USA; (A.S.W.); (J.M.K.)
| | - Martina Benešová-Schäfer
- Research Group Molecular Biology of Systemic Radiotherapy/Translational Radiotheranostics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany; (R.C.W.); (M.A.); (G.B.); (H.T.)
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Kang HJ, Kim M, Kwak YK, Lee SJ. Predictive Factors and the Role of Conventionally Fractionated Radiation Therapy for Bone Metastasis from Renal Cell Carcinoma in the Era of Targeted Therapy. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:1049. [PMID: 39064478 PMCID: PMC11278518 DOI: 10.3390/medicina60071049] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/21/2024] [Revised: 06/17/2024] [Accepted: 06/25/2024] [Indexed: 07/28/2024]
Abstract
Background and Objectives: Despite rapid advances in targeted therapies for renal cell carcinoma (RCC), bone metastases remain a major problem that significantly increases morbidity and reduces patients' quality of life. Conventional fractionated radiotherapy (CF-RT) is known to be an important local treatment option for bone metastases; however, bone metastases from RCC have traditionally been considered resistant to CF-RT. We aimed to investigate the effectiveness of CF-RT for symptomatic bone metastasis from RCC and identify the predictive factors associated with treatment outcomes in the targeted therapy era. Materials and Methods: Between January 2011 and December 2023, a total of 73 lesions in 50 patients treated with a palliative course of CF-RT for symptomatic bone metastasis from RCC were evaluated, and 62 lesions in 41 patients were included in this study. Forty-five lesions (72.6%) were treated using targeted therapy during CF-RT. The most common radiation dose fractionations were 30 gray (Gy) in 10 fractions (50%) and 39 Gy in 13 fractions (16.1%). Results: Pain relief was experienced in 51 of 62 lesions (82.3%), and the 12-month local control (LC) rate was 61.2%. Notably, 72.6% of the treatment course in this study was combined with targeted therapy. The 12-month LC rate was 74.8% in patients who received targeted therapy and only 10.9% in patients without targeted therapy (p < 0.001). Favorable Eastern Cooperative Oncology Group performance status (p = 0.026) and pain response (p < 0.001) were independent predictors of improved LC. Radiation dose escalation improved the LC in radiosensitive patients. A consistent treatment response was confirmed in patients with multiple treatment courses. Conclusions: CF-RT enhances pain relief and LC when combined with targeted therapy. Patients who responded well to initial treatment generally showed consistent responses to subsequent CF-RT for additional painful bone lesions. CF-RT could therefore be an excellent complementary local treatment modality for targeted therapy.
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Affiliation(s)
- Hye Jin Kang
- Department of Radiation Oncology, Incheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea; (M.K.); (Y.-K.K.); (S.J.L.)
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13
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Radonic S, Schneider U, Besserer J, Meier VS, Rohrer Bley C. Risk adaptive planning with biology-based constraints may lead to higher tumor control probability in tumors of the canine brain: A planning study. Phys Med 2024; 119:103317. [PMID: 38430675 DOI: 10.1016/j.ejmp.2024.103317] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2023] [Revised: 11/27/2023] [Accepted: 02/06/2024] [Indexed: 03/05/2024] Open
Abstract
BACKGROUND Classical radiation protocols are guided by physical dose delivered homogeneously over the target. Protocols are chosen to keep normal tissue complication probability (NTCP) at an acceptable level. Organs at risk (OAR) adjacent to the target volume could lead to underdosage of the tumor and a decrease of tumor control probability (TCP). The intent of our study was to explore a biology-based dose escalation: by keeping NTCP for OAR constant, radiation dose was to be maximized, allowing to result in heterogeneous dose distributions. METHODS We used computed tomography datasets of 25 dogs with brain tumors, previously treated with 10x4 Gy (40 Gy to PTV D50). We generated 3 plans for each patient: A) original treatment plan with homogeneous dose distribution, B) heterogeneous dose distribution with strict adherence to the same NTCPs as in A), and C) heterogeneous dose distribution with adherence to NTCP <5%. For plan comparison, TCPs and TCP equivalent doses (homogenous target dose which results in the same TCP) were calculated. To enable the use of the generalized equivalent uniform dose (gEUD) metric of the tumor target in plan optimization, the calculated TCP values were used to obtain the volume effect parameter a. RESULTS As intended, NTCPs for all OARs did not differ from plan A) to B). In plan C), however, NTCPs were significantly higher for brain (mean 2.5% (SD±1.9, 95%CI: 1.7,3.3), p<0.001), optic chiasm (mean 2.0% (SD±2.2, 95%CI: 1.0,2.8), p=0.010) compared to plan A), but no significant increase was found for the brainstem. For 24 of 25 of the evaluated patients, the heterogenous plans B) and C) led to an increase in target dose and projected increase in TCP compared to the homogenous plan A). Furthermore, the distribution of the projected individual TCP values as a function of the dose was found to be in good agreement with the population TCP model. CONCLUSION Our study is a first step towards risk-adaptive radiation dose optimization. This strategy utilizes a biologic objective function based on TCP and NTCP instead of an objective function based on physical dose constraints.
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Affiliation(s)
- Stephan Radonic
- Department of Physics, University of Zurich, Zurich, Switzerland; Division of Radiation Oncology, Small Animal Department, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland.
| | - Uwe Schneider
- Department of Physics, University of Zurich, Zurich, Switzerland; Radiotherapie Hirslanden AG, Rain 34, Aarau, Switzerland
| | - Jürgen Besserer
- Department of Physics, University of Zurich, Zurich, Switzerland; Radiotherapie Hirslanden AG, Rain 34, Aarau, Switzerland
| | - Valeria S Meier
- Department of Physics, University of Zurich, Zurich, Switzerland; Division of Radiation Oncology, Small Animal Department, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland
| | - Carla Rohrer Bley
- Division of Radiation Oncology, Small Animal Department, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland
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14
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Rajurkar S, Verma T, Mishra SP, Bhatt MLB. Novel Artificial Intelligence Tool for Real-time Patient Identification to Prevent Misidentification in Health Care. J Med Phys 2024; 49:41-48. [PMID: 38828072 PMCID: PMC11141754 DOI: 10.4103/jmp.jmp_106_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2023] [Revised: 02/12/2024] [Accepted: 02/16/2024] [Indexed: 06/05/2024] Open
Abstract
Purpose Errors in the identification of true patients in a health-care facility may result in the wrong dose or dosage being given to the wrong patient at the wrong site during radiotherapy sessions, radiopharmaceutical administration, radiological scans, etc. The aim of this article is to reduce the error in the identification of correct patients by implementation of the Python deep learning-based real-time patient identification program. Materials and Methods The authors utilized and installed Anaconda Prompt (miniconda 3), Python (version 3.9.12), and Visual Studio Code (version 1.71.0) for the design of the patient identification program. In the field of view, the area of interest is merely face detection. The overall performance of the developed program is accomplished over three steps, namely image data collection, data transfer, and data analysis, respectively. The patient identification tool was developed using the OpenCV library for face recognition. Results This program provides real-time patient identification information, together with the other preset parameters such as disease site, with a precision of 0.92%, recall rate of 0.80%, and specificity of 0.90%. Furthermore, the accuracy of the program was found to be 0.84%. The output of the in-house developed program as "Unknown" is provided if a patient's relative or an unknown person is found in restricted region. Interpretation and Conclusions This Python-based program is beneficial for confirming the patient's identity, without manual interventions, just before therapy, administering medications, and starting other medical procedures, among other things, to prevent unintended medical and health-related complications that may arise as a result of misidentification.
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Affiliation(s)
- Shriram Rajurkar
- Department of Radiotherapy, King George’s Medical University, UP, India
| | - Teerthraj Verma
- Department of Radiotherapy, King George’s Medical University, UP, India
| | - S P Mishra
- Department of Radiation Oncology, Dr RMLIMS, Lucknow, India
| | - MLB Bhatt
- Department of Radiotherapy, King George’s Medical University, UP, India
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15
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Beckers C, Pruschy M, Vetrugno I. Tumor hypoxia and radiotherapy: A major driver of resistance even for novel radiotherapy modalities. Semin Cancer Biol 2024; 98:19-30. [PMID: 38040401 DOI: 10.1016/j.semcancer.2023.11.006] [Citation(s) in RCA: 32] [Impact Index Per Article: 32.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2023] [Revised: 11/16/2023] [Accepted: 11/22/2023] [Indexed: 12/03/2023]
Abstract
Hypoxia in solid tumors is an important predictor of poor clinical outcome to radiotherapy. Both physicochemical and biological processes contribute to a reduced sensitivity of hypoxic tumor cells to ionizing radiation and hypoxia-related treatment resistances. A conventional low-dose fractionated radiotherapy regimen exploits iterative reoxygenation in between the individual fractions, nevertheless tumor hypoxia still remains a major hurdle for successful treatment outcome. The technological advances achieved in image guidance and highly conformal dose delivery make it nowadays possible to prescribe larger doses to the tumor as part of single high-dose or hypofractionated radiotherapy, while keeping an acceptable level of normal tissue complication in the co-irradiated organs at risk. However, we insufficiently understand the impact of tumor hypoxia to single high-doses of RT and hypofractionated RT. So-called FLASH radiotherapy, which delivers ionizing radiation at ultrahigh dose rates (> 40 Gy/sec), has recently emerged as an important breakthrough in the radiotherapy field to reduce normal tissue toxicity compared to irradiation at conventional dose rates (few Gy/min). Not surprisingly, oxygen consumption and tumor hypoxia also seem to play an intriguing role for FLASH radiotherapy. Here we will discuss the role of tumor hypoxia for radiotherapy in general and in the context of novel radiotherapy treatment approaches.
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Affiliation(s)
- Claire Beckers
- Laboratory for Applied Radiobiology, Department of Radiation Oncology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Martin Pruschy
- Laboratory for Applied Radiobiology, Department of Radiation Oncology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
| | - Irene Vetrugno
- Laboratory for Applied Radiobiology, Department of Radiation Oncology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
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16
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Vorbach SM, Mangesius J, Dejaco D, Seppi T, Santer M, Zur Nedden S, Sarcletti MP, Pointner MJ, Hart TJ, Riechelmann H, Ganswindt U, Nevinny-Stickel M. Survival, Treatment Outcome, and Safety of Multiple and Repeated Courses of Stereotactic Body Radiotherapy for Pulmonary Oligometastases of Head and Neck Squamous Cell Carcinoma. Cancers (Basel) 2023; 15:5253. [PMID: 37958426 PMCID: PMC10647772 DOI: 10.3390/cancers15215253] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2023] [Revised: 10/17/2023] [Accepted: 10/30/2023] [Indexed: 11/15/2023] Open
Abstract
Current literature regarding survival and treatment outcome of SBRT in patients with pulmonary oligometastatic head and neck squamous cell carcinoma (HNSCC) is limited. Additionally, most of the published studies include metastatic lesions deriving also from primaries with histologies other than SCC when investigating the outcome of SBRT. The aim of the present retrospective study is to explore local control (LC) of treated metastases, progression-free survival (PFS), and overall survival (OS) of exclusively pulmonary oligometastatic HNSCC-patients treated with SBRT. Between 2006 and 2021, a total of 46 patients were treated with SBRT for a maximum of four pulmonary oligometastases (PM) concurrently (mean PM per patient = 2.0; range 1 to 6 PM, total of 92). Of these, 17 patients (37.0%) developed new pulmonary metastases after their first SBRT. Repeated courses of SBRT were required once in 15 patients (88.2%) and twice in 2 patients (11.8%). Median follow-up was 17 months (range, 0-109 months). One year after completion of SBRT, LC rate, PFS, and OS were 98.7%, 37.9%, and 79.5%, respectively. After two years, LC rate, PFS, and OS were 98.7%, 28.7%, and 54.9%; as well as 98.7%, 16.7%, and 31.0% after five years. Radiochemotherapy (HR 2.72, p < 0.001) or radiotherapy as primary treatment (HR 8.60; p = 0.003), as well as reduced patient performance status (HR 48.30, p = 0.002), were associated with lower PFS. Inferior OS correlated with poor performance status (HR 198.51, p < 0.001) and surgery followed by radiochemotherapy (HR 4.18, p = 0.032) as primary treatment, as well as radiotherapy alone (HR 7.11, p = 0.020). Treatment of more than one PM is an independent predictor of impaired OS (HR 3.30, p = 0.016). SBRT of HNSCC-derived PMs results in excellent LC rates and encouraging OS rates of 54.9% at two years along with good tolerability (no more than grade 2 toxicities). Favourable outcome and low toxicity also apply to repeated courses of SBRT of newly emerging PMs.
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Affiliation(s)
- Samuel Moritz Vorbach
- Department of Radiation-Oncology, Medical University of Innsbruck, 6020 Innsbruck, Austria; (S.M.V.); (T.S.); (M.P.S.); (M.J.P.); (T.J.H.); (U.G.); (M.N.-S.)
| | - Julian Mangesius
- Department of Radiation-Oncology, Medical University of Innsbruck, 6020 Innsbruck, Austria; (S.M.V.); (T.S.); (M.P.S.); (M.J.P.); (T.J.H.); (U.G.); (M.N.-S.)
| | - Daniel Dejaco
- Department of Otorhinolaryngology—Head and Neck Surgery, Medical University of Innsbruck, 6020 Innsbruck, Austria; (D.D.); (M.S.); (H.R.)
| | - Thomas Seppi
- Department of Radiation-Oncology, Medical University of Innsbruck, 6020 Innsbruck, Austria; (S.M.V.); (T.S.); (M.P.S.); (M.J.P.); (T.J.H.); (U.G.); (M.N.-S.)
| | - Matthias Santer
- Department of Otorhinolaryngology—Head and Neck Surgery, Medical University of Innsbruck, 6020 Innsbruck, Austria; (D.D.); (M.S.); (H.R.)
| | - Stephanie Zur Nedden
- CCB-Biocenter, Institute of Neurobiochemistry, Medial University of Innsbruck, 6020 Innsbruck, Austria;
| | - Manuel Paolo Sarcletti
- Department of Radiation-Oncology, Medical University of Innsbruck, 6020 Innsbruck, Austria; (S.M.V.); (T.S.); (M.P.S.); (M.J.P.); (T.J.H.); (U.G.); (M.N.-S.)
| | - Martin Josef Pointner
- Department of Radiation-Oncology, Medical University of Innsbruck, 6020 Innsbruck, Austria; (S.M.V.); (T.S.); (M.P.S.); (M.J.P.); (T.J.H.); (U.G.); (M.N.-S.)
| | - Tilmann Jakob Hart
- Department of Radiation-Oncology, Medical University of Innsbruck, 6020 Innsbruck, Austria; (S.M.V.); (T.S.); (M.P.S.); (M.J.P.); (T.J.H.); (U.G.); (M.N.-S.)
| | - Herbert Riechelmann
- Department of Otorhinolaryngology—Head and Neck Surgery, Medical University of Innsbruck, 6020 Innsbruck, Austria; (D.D.); (M.S.); (H.R.)
| | - Ute Ganswindt
- Department of Radiation-Oncology, Medical University of Innsbruck, 6020 Innsbruck, Austria; (S.M.V.); (T.S.); (M.P.S.); (M.J.P.); (T.J.H.); (U.G.); (M.N.-S.)
| | - Meinhard Nevinny-Stickel
- Department of Radiation-Oncology, Medical University of Innsbruck, 6020 Innsbruck, Austria; (S.M.V.); (T.S.); (M.P.S.); (M.J.P.); (T.J.H.); (U.G.); (M.N.-S.)
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17
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Mheid S, Allen S, Ng SSW, Hall WA, Sanford NN, Aguilera TA, Elamir AM, Bahij R, Intven MPW, Radhakrishna G, Mohamad I, De Leon J, Tan H, Lewis S, Gani C, Stanecu T, Dell’Acqua V, Hosni A. Local Control Following Stereotactic Body Radiation Therapy for Liver Oligometastases: Lessons from a Quarter Century. Curr Oncol 2023; 30:9230-9243. [PMID: 37887567 PMCID: PMC10605011 DOI: 10.3390/curroncol30100667] [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: 08/01/2023] [Revised: 09/14/2023] [Accepted: 09/30/2023] [Indexed: 10/28/2023] Open
Abstract
The utilization of stereotactic body radiation therapy for the treatment of liver metastasis has been widely studied and has demonstrated favorable local control outcomes. However, several predictive factors play a crucial role in the efficacy of stereotactic body radiation therapy, such as the number and size (volume) of metastatic liver lesions, the primary tumor site (histology), molecular biomarkers (e.g., KRAS and TP53 mutation), the use of systemic therapy prior to SBRT, the radiation dose, and the use of advanced technology and organ motion management during SBRT. These prognostic factors need to be considered when clinical trials are designed to evaluate the efficacy of SBRT for liver metastases.
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Affiliation(s)
- Sara Mheid
- Department of Radiation Oncology, University of Toronto, Princess Margaret Cancer Centre, Toronto, ON M5G 2M9, Canada; (S.M.); (T.S.)
| | - Stefan Allen
- Department of Radiation Oncology, Dalhousie University, Nova Scotia Health, Halifax, NS B3H 4R2, Canada;
| | - Sylvia S. W. Ng
- Department of Radiation Oncology, University of Toronto, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, ON M4N 3M5, Canada;
| | - William A. Hall
- Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI 53226, USA;
| | - Nina N. Sanford
- Department of Radiation Oncology, University of Texas Southwestern, Dallas, TX 75235, USA; (N.N.S.); (T.A.A.); (A.M.E.)
| | - Todd A. Aguilera
- Department of Radiation Oncology, University of Texas Southwestern, Dallas, TX 75235, USA; (N.N.S.); (T.A.A.); (A.M.E.)
| | - Ahmed M. Elamir
- Department of Radiation Oncology, University of Texas Southwestern, Dallas, TX 75235, USA; (N.N.S.); (T.A.A.); (A.M.E.)
| | - Rana Bahij
- Department of Oncology, Odense University Hospital, 5000 Odense, Denmark;
| | - Martijn P. W. Intven
- Department of Radiotherapy, Division Imaging and Oncology, University Medical Centre, 3584 CX Utrecht, The Netherlands;
| | - Ganesh Radhakrishna
- Department of Radiotherapy, The Christie NHS Foundation Trust, Manchester M20 4BX, UK;
| | - Issa Mohamad
- Department of Radiation Oncology, King Hussein Cancer Center, Amman 11941, Jordan;
| | | | - Hendrick Tan
- Department of Radiation Oncology, Fiona Stanley Hospital, Perth, WA 6150, Australia;
- GenesisCare, Perth, WA 6150, Australia
| | - Shirley Lewis
- Department of Radiotherapy and Oncology, Manipal Comprehensive Cancer Care Centre, Kasturba Medical College, Manipal Academy of Higher Education, Manipal 576104, India;
| | - Cihan Gani
- Department of Radiation Oncology, University Hospital Tübingen, 72076 Tübingen, Germany;
| | - Teo Stanecu
- Department of Radiation Oncology, University of Toronto, Princess Margaret Cancer Centre, Toronto, ON M5G 2M9, Canada; (S.M.); (T.S.)
| | - Veronica Dell’Acqua
- Medical Affairs and Clinical Research, Linac-Based RT, Elekta Milan, 20864 Lombardy, Italy;
| | - Ali Hosni
- Department of Radiation Oncology, University of Toronto, Princess Margaret Cancer Centre, Toronto, ON M5G 2M9, Canada; (S.M.); (T.S.)
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18
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Malatesta T, Scaggion A, Giglioli FR, Belmonte G, Casale M, Colleoni P, Falco MD, Giuliano A, Linsalata S, Marino C, Moretti E, Richetto V, Sardo A, Russo S, Mancosu P. Patient specific quality assurance in SBRT: a systematic review of measurement-based methods. Phys Med Biol 2023; 68:21TR01. [PMID: 37625437 DOI: 10.1088/1361-6560/acf43a] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2023] [Accepted: 08/25/2023] [Indexed: 08/27/2023]
Abstract
This topical review focuses on Patient-Specific Quality Assurance (PSQA) approaches to stereotactic body radiation therapy (SBRT). SBRT requires stricter accuracy than standard radiation therapy due to the high dose per fraction and the limited number of fractions. The review considered various PSQA methods reported in 36 articles between 01/2010 and 07/2022 for SBRT treatment. In particular comparison among devices and devices designed for SBRT, sensitivity and resolution, verification methodology, gamma analysis were specifically considered. The review identified a list of essential data needed to reproduce the results in other clinics, highlighted the partial miss of data reported in scientific papers, and formulated recommendations for successful implementation of a PSQA protocol.
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Affiliation(s)
- Tiziana Malatesta
- Medical Physics Unit, Department of Radiotherapy and Medical Oncology and Radiology, Fatebenefratelli Isola Tiberina-Gemelli Isola Hospital, Rome, Italy
| | - Alessandro Scaggion
- Medical Physics Department, Veneto Institute of Oncology IOV - IRCCS, Padova, Italy
| | | | - Gina Belmonte
- Medical Physics Department, San Luca Hospital, Lucca, Italy
| | - Michelina Casale
- Medical Physics Unit, Azienda Ospedaliera 'Santa Maria', Terni, Italy
| | - Paolo Colleoni
- UOC Medical Physics Unit-ASST Papa Giovanni XXIII, Bergamo, Italy
| | - Maria Daniela Falco
- Department of Radiation Oncology, 'SS. Annunziata' Hospital, 'G. D'Annunzio' University, Chieti, Italy
| | - Alessia Giuliano
- Medical Physics Unit, Pisa University Hospital 'Azienda Ospedaliero-Universitaria Pisana', Pisa, Italy
| | - Stefania Linsalata
- Medical Physics Unit, Pisa University Hospital 'Azienda Ospedaliero-Universitaria Pisana', Pisa, Italy
| | - Carmelo Marino
- Medical Physics and Radioprotection Unit, Humanitas Istituto Clinico Catanese, Misterbianco (CT), Italy
| | - Eugenia Moretti
- Division of Medical Physics, Department of Oncology, ASUFC Udine, Italy
| | - Veronica Richetto
- Medical Physics Unit, A.O.U. Città della Salute e della Scienza di Torino, Torino, Italy
| | - Anna Sardo
- UOSD Medical Physics, ASLCN2, Verduno, Italy
| | - Serenella Russo
- Medical Physics Unit, Azienda USL Toscana Centro, Florence, Italy
| | - Pietro Mancosu
- Medical Physics Unit of Radiotherapy Department, IRCCS Humanitas Research Hospital, Rozzano - Milano, Italy
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19
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Galassi C, Klapp V, Formenti SC, Demaria S, Galluzzi L. Immunologically relevant effects of radiation therapy on the tumor microenvironment. Essays Biochem 2023; 67:979-989. [PMID: 37199227 PMCID: PMC10543618 DOI: 10.1042/ebc20220248] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2023] [Revised: 04/06/2023] [Accepted: 04/21/2023] [Indexed: 05/19/2023]
Abstract
Focal radiation therapy (RT) has been successfully employed to clinically manage multiple types of cancer for more than a century. Besides being preferentially cytotoxic for malignant cells over their nontransformed counterparts, RT elicits numerous microenvironmental alterations that appear to factor into its therapeutic efficacy. Here, we briefly discuss immunostimulatory and immunosuppressive microenvironmental changes elicited by RT and their impact on tumor recognition by the host immune system.
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Affiliation(s)
- Claudia Galassi
- Department of Radiation Oncology, Weill Cornell Medical College, New York, NY, USA
| | - Vanessa Klapp
- Tumor Stroma Interactions, Department of Cancer Research, Luxembourg Institute of Health, Luxembourg, Luxembourg
- Faculty of Science, Technology and Medicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg
| | - Silvia C. Formenti
- Department of Radiation Oncology, Weill Cornell Medical College, New York, NY, USA
- Department of Medicine, Weill Cornell Medical College, New York, NY, USA
- Sandra and Edward Meyer Cancer Center, New York, NY, USA
| | - Sandra Demaria
- Department of Radiation Oncology, Weill Cornell Medical College, New York, NY, USA
| | - Lorenzo Galluzzi
- Department of Radiation Oncology, Weill Cornell Medical College, New York, NY, USA
- Sandra and Edward Meyer Cancer Center, New York, NY, USA
- Caryl and Israel Englander Institute for Precision Medicine, New York, NY, USA
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20
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Wei Z, Chi J, Cao P, Jin Y, Li X, Ye X. Microwave ablation with a blunt-tip antenna for pulmonary ground-glass nodules: a retrospective, multicenter, case-control study. LA RADIOLOGIA MEDICA 2023; 128:1061-1069. [PMID: 37458905 PMCID: PMC10474204 DOI: 10.1007/s11547-023-01672-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/08/2023] [Accepted: 06/25/2023] [Indexed: 09/02/2023]
Abstract
PURPOSE A previous small-sample study verified that a blunt-tip antenna reduced hemorrhage during microwave ablation. We conducted this large-sample, multicenter, case-control study to further verify the efficacy and safety of microwave ablation with a blunt-tip antenna for ground-glass nodules. MATERIALS AND METHODS Patients with pulmonary ground-glass nodules were treated with either a sharp-tip (Group A) or blunt-tip antenna (Group B). A total of 147 and 150 patients were retrospectively allocated to Groups A and Group B, respectively. Group A patients underwent 151 procedures, and Group B patients underwent 153 procedures. We assessed the technical success, technique efficacy, and complications. RESULTS Technical success and overall technique efficacy were achieved in all patients (100%). Major complications of pneumothorax were more commonly observed in Group A than in Group B (19.7% vs. 2.0%, p < 0.001). Minor complications, such as intrapulmonary hemorrhage (2.0% vs. 9.5%, p = 0.005) and hemothorax (0.0% vs. 2.7%, p = 0.049), occurred less frequently in Group B compared to Group A. CONCLUSION In the treatment of ground-glass nodules, microwave ablation with a blunt-tip antenna had equal efficacy compared to microwave ablation with a sharp-tip antenna but had a decreased number of hemorrhage and hemothorax complications.
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Affiliation(s)
- Zhigang Wei
- Department of Oncology, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Shandong Lung Cancer Institute, Jinan, 250014, Shandong, China
- Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
| | - Jiachang Chi
- Department of Interventional Oncology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, 160# Pujian Road, Shanghai, 200127, China
| | - Pikun Cao
- Department of Oncology, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Shandong Lung Cancer Institute, Jinan, 250014, Shandong, China
| | - Yong Jin
- Department of Interventional Therapy, The Second Affiliated Hospital of Soochow University, Suzhou, 215000, China.
| | - Xiaoguang Li
- Department of Minimally Invasive Tumor Therapies Center, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, 100370, China.
| | - Xin Ye
- Department of Oncology, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Shandong Lung Cancer Institute, Jinan, 250014, Shandong, China.
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21
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Pardo-Montero J, González-Crespo I, Gómez-Caamaño A, Gago-Arias A. Radiobiological Meta-Analysis of the Response of Prostate Cancer to Different Fractionations: Evaluation of the Linear-Quadratic Response at Large Doses and the Effect of Risk and ADT. Cancers (Basel) 2023; 15:3659. [PMID: 37509320 PMCID: PMC10377316 DOI: 10.3390/cancers15143659] [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: 05/22/2023] [Revised: 07/04/2023] [Accepted: 07/12/2023] [Indexed: 07/30/2023] Open
Abstract
The purpose of this work was to investigate the response of prostate cancer to different radiotherapy schedules, including hypofractionation, to evaluate potential departures from the linear-quadratic (LQ) response, to obtain the best-fitting parameters for low-(LR), intermediate-(IR), and high-risk (HR) prostate cancer and to investigate the effect of ADT on the radiobiological response. We constructed a dataset of the dose-response containing 87 entries/16,536 patients (35/5181 LR, 32/8146 IR, 20/3209 HR), with doses per fraction ranging from 1.8 to 10 Gy. These data were fit to tumour control probability models based on the LQ model, linear-quadratic-linear (LQL) model, and a modification of the LQ (LQmod) model accounting for increasing radiosensitivity at large doses. Fits were performed with the maximum likelihood expectation methodology, and the Akaike information criterion (AIC) was used to compare the models. The AIC showed that the LQ model was superior to the LQL and LQmod models for all risks, except for IR, where the LQL model outperformed the other models. The analysis showed a low α/β for all risks: 2.0 Gy for LR (95% confidence interval: 1.7-2.3), 3.4 Gy for IR (3.0-4.0), and 2.8 Gy for HR (1.4-4.2). The best fits did not show proliferation for LR and showed moderate proliferation for IR/HR. The addition of ADT was consistent with a suppression of proliferation. In conclusion, the LQ model described the response of prostate cancer better than the alternative models. Only for IR, the LQL model outperformed the LQ model, pointing out a possible saturation of radiation damage with increasing dose. This study confirmed a low α/β for all risks.
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Affiliation(s)
- Juan Pardo-Montero
- Group of Medical Physics and Biomathematics, Instituto de Investigación Sanitaria de Santiago (IDIS), 15706 Santiago de Compostela, Spain
- Department of Medical Physics, Complexo Hospitalario Universitario de Santiago de Compostela, 15706 Santiago de Compostela, Spain
| | - Isabel González-Crespo
- Group of Medical Physics and Biomathematics, Instituto de Investigación Sanitaria de Santiago (IDIS), 15706 Santiago de Compostela, Spain
- Department of Applied Mathematics, Universidade de Santiago de Compostela, 15705 Santiago de Compostela, Spain
| | - Antonio Gómez-Caamaño
- Department of Radiation Oncology, Complexo Hospitalario Universitario de Santiago de Compostela, 15706 Santiago de Compostela, Spain
| | - Araceli Gago-Arias
- Group of Medical Physics and Biomathematics, Instituto de Investigación Sanitaria de Santiago (IDIS), 15706 Santiago de Compostela, Spain
- Department of Medical Physics, Complexo Hospitalario Universitario de Santiago de Compostela, 15706 Santiago de Compostela, Spain
- Institute of Physics, Pontificia Universidad Católica de Chile, Santiago de Chile 7820436, Chile
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22
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Dillon O, Reynolds T, O'Brien RT. X-ray source arrays for volumetric imaging during radiotherapy treatment. Sci Rep 2023; 13:9776. [PMID: 37328551 PMCID: PMC10275902 DOI: 10.1038/s41598-023-36708-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2022] [Accepted: 06/08/2023] [Indexed: 06/18/2023] Open
Abstract
This work presents a novel hardware configuration for radiotherapy systems to enable fast 3D X-ray imaging before and during treatment delivery. Standard external beam radiotherapy linear accelerators (linacs) have a single X-ray source and detector located at ± 90° from the treatment beam respectively. The entire system can be rotated around the patient acquiring multiple 2D X-ray images to create a 3D cone-beam Computed Tomography (CBCT) image before treatment delivery to ensure the tumour and surrounding organs align with the treatment plan. Scanning with a single source is slow relative to patient respiration or breath holds and cannot be performed during treatment delivery, limiting treatment delivery accuracy in the presence of patient motion and excluding some patients from concentrated treatment plans that would be otherwise expected to have improved outcomes. This simulation study investigated whether recent advances in carbon nanotube (CNT) field emission source arrays, high frame rate (60 Hz) flat panel detectors and compressed sensing reconstruction algorithms could circumvent imaging limitations of current linacs. We investigated a novel hardware configuration incorporating source arrays and high frame rate detectors into an otherwise standard linac. We investigated four potential pre-treatment scan protocols that could be achieved in a 17 s breath hold or 2-10 1 s breath holds. Finally, we demonstrated for the first time volumetric X-ray imaging during treatment delivery by using source arrays, high frame rate detectors and compressed sensing. Image quality was assessed quantitatively over the CBCT geometric field of view as well as across each axis through the tumour centroid. Our results demonstrate that source array imaging enables larger volumes to be imaged with acquisitions as short as 1 s albeit with reduced image quality arising from lower photon flux and shorter imaging arcs.
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Affiliation(s)
- Owen Dillon
- Faculty of Medicine and Health, Image X Institute, University of Sydney, Sydney, 2015, Australia.
| | - Tess Reynolds
- Faculty of Medicine and Health, Image X Institute, University of Sydney, Sydney, 2015, Australia
| | - Ricky T O'Brien
- School of Health and Biomedical Sciences, Medical Imaging Facility, Royal Melbourne Institute of Technology, Melbourne, 3083, Australia
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23
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Galluzzi L, Aryankalayil MJ, Coleman CN, Formenti SC. Emerging evidence for adapting radiotherapy to immunotherapy. Nat Rev Clin Oncol 2023:10.1038/s41571-023-00782-x. [PMID: 37280366 DOI: 10.1038/s41571-023-00782-x] [Citation(s) in RCA: 125] [Impact Index Per Article: 62.5] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/09/2023] [Indexed: 06/08/2023]
Abstract
Immunotherapy has revolutionized the clinical management of many malignancies but is infrequently associated with durable objective responses when used as a standalone treatment approach, calling for the development of combinatorial regimens with superior efficacy and acceptable toxicity. Radiotherapy, the most commonly used oncological treatment, has attracted considerable attention as a combination partner for immunotherapy owing to its well-known and predictable safety profile, widespread clinical availability, and potential for immunostimulatory effects. However, numerous randomized clinical trials investigating radiotherapy-immunotherapy combinations have failed to demonstrate a therapeutic benefit compared with either modality alone. Such a lack of interaction might reflect suboptimal study design, choice of end points and/or administration of radiotherapy according to standard schedules and target volumes. Indeed, radiotherapy has empirically evolved towards radiation doses and fields that enable maximal cancer cell killing with manageable toxicity to healthy tissues, without much consideration of potential radiation-induced immunostimulatory effects. Herein, we propose the concept that successful radiotherapy-immunotherapy combinations might require modifications of standard radiotherapy regimens and target volumes to optimally sustain immune fitness and enhance the antitumour immune response in support of meaningful clinical benefits.
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Affiliation(s)
- Lorenzo Galluzzi
- Department of Radiation Oncology, Weill Cornell Medical College, New York, NY, USA
- Sandra and Edward Meyer Cancer Center, New York, NY, USA
- Caryl and Israel Englander Institute for Precision Medicine, New York, NY, USA
| | - Molykutty J Aryankalayil
- Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA
| | - C Norman Coleman
- Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA
| | - Silvia C Formenti
- Department of Radiation Oncology, Weill Cornell Medical College, New York, NY, USA.
- Sandra and Edward Meyer Cancer Center, New York, NY, USA.
- Department of Medicine, Weill Cornell Medical College, New York, NY, USA.
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24
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Liew LP, Shome A, Wong WW, Hong CR, Hicks KO, Jamieson SMF, Hay MP. Design, Synthesis and Anticancer Evaluation of Nitroimidazole Radiosensitisers. Molecules 2023; 28:molecules28114457. [PMID: 37298933 DOI: 10.3390/molecules28114457] [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: 05/05/2023] [Revised: 05/29/2023] [Accepted: 05/29/2023] [Indexed: 06/12/2023] Open
Abstract
The role of hypoxic tumour cells in resistance to radiotherapy, and in suppression of immune response, continues to endorse tumour hypoxia as a bona fide, yet largely untapped, drug target. Radiotherapy innovations such as stereotactic body radiotherapy herald new opportunities for classical oxygen-mimetic radiosensitisers. Only nimorazole is used clinically as a radiosensitiser, and there is a dearth of new radiosensitisers in development. In this report, we augment previous work to present new nitroimidazole alkylsulfonamides and we document their cytotoxicity and ability to radiosensitise anoxic tumour cells in vitro. We compare radiosensitisation with etanidazole and earlier nitroimidazole sulfonamide analogues and we identify 2-nitroimidazole and 5-nitroimidazole analogues with marked tumour radiosensitisation in ex vivo assays of surviving clonogens and with in vivo tumour growth inhibition.
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Affiliation(s)
- Lydia P Liew
- Auckland Cancer Society Research Centre, The University of Auckland, Auckland 1023, New Zealand
- Maurice Wilkins Centre for Molecular Biodiscovery, The University of Auckland, Auckland 1010, New Zealand
| | - Avik Shome
- Auckland Cancer Society Research Centre, The University of Auckland, Auckland 1023, New Zealand
- Department of Ophthalmology, The University of Auckland, Auckland 1023, New Zealand
| | - Way W Wong
- Auckland Cancer Society Research Centre, The University of Auckland, Auckland 1023, New Zealand
| | - Cho R Hong
- Auckland Cancer Society Research Centre, The University of Auckland, Auckland 1023, New Zealand
- Maurice Wilkins Centre for Molecular Biodiscovery, The University of Auckland, Auckland 1010, New Zealand
| | - Kevin O Hicks
- Auckland Cancer Society Research Centre, The University of Auckland, Auckland 1023, New Zealand
- Maurice Wilkins Centre for Molecular Biodiscovery, The University of Auckland, Auckland 1010, New Zealand
| | - Stephen M F Jamieson
- Auckland Cancer Society Research Centre, The University of Auckland, Auckland 1023, New Zealand
- Maurice Wilkins Centre for Molecular Biodiscovery, The University of Auckland, Auckland 1010, New Zealand
- Department of Pharmacology and Clinical Pharmacology, The University of Auckland, Auckland 1023, New Zealand
| | - Michael P Hay
- Auckland Cancer Society Research Centre, The University of Auckland, Auckland 1023, New Zealand
- Maurice Wilkins Centre for Molecular Biodiscovery, The University of Auckland, Auckland 1010, New Zealand
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25
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Li X, Zhu Z, Liu J, Gao Y, Xiao Y, Fang Z, Liu Q, Liu X, Hu C, Ma F, Zeng M, Liu Z, Hu L, Liu N, Xiang F, Hu X, Huang L, Zhou S. Septal radioablation therapy for patients with hypertrophic obstructive cardiomyopathy: first-in-human study. EUROPEAN HEART JOURNAL OPEN 2023; 3:oead052. [PMID: 37503357 PMCID: PMC10371052 DOI: 10.1093/ehjopen/oead052] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/10/2023] [Revised: 04/03/2023] [Accepted: 04/12/2023] [Indexed: 07/29/2023]
Abstract
Aims There is still no non-invasive septal reduction therapy for patients with hypertrophic obstructive cardiomyopathy (HOCM). This study aimed to investigate the feasibility, safety, and efficacy of stereotactic body radiotherapy (SBRT) in patients with drug-refractory symptomatic HOCM. Methods and results The radiation target of ventricular septum was determined by multiple anatomical imaging. Stereotactic body radiotherapy was performed with standard techniques. Patients were treated with a single fraction of 25 Gy, followed up at 1, 3, 6, and 12 months by clinical visit. Five patients were enrolled and completed the 12 months follow-up. The mean radioablation time was 21.6 min, and the mean target volume was 10.5 cm3. All five patients survived and showed improvements in symptoms after SBRT. At 12 months post-SBRT, the echocardiography-derived left ventricular outflow tract gradient decreased from 88 mmHg (range, 63-105) to 52 mmHg (range, 36-66) at rest and from 101 mmHg (range, 72-121) to 74 mmHg (range, 65-100) after Valsalva. The end-diastolic thickness of the targeted septum reduced from 23.7 mm (range, 20.3-29) to 22.4 mm (range, 19.7-26.5); 6 min walking distance increased from 190.4 m (range, 50-370) to 412.0 m (range, 320-480). All patients presented with new fibrosis in the irradiated septum area. No radiation-related complications were observed during SBRT and up to 12 months post procedure. Conclusion The current study suggests that SBRT might be a feasible radioablation therapeutic option for patients with drug-refractory symptomatic HOCM. Trial registration ClinicalTrials.gov Identifier: NCT04686487.
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Affiliation(s)
| | | | - Jun Liu
- Radiology Department, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Yawen Gao
- Oncology Department, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Yichao Xiao
- Department of Cardiovascular Medicine, The Second Xiangya Hospital, Central South University, 139 Mid-Renmin Road, Changsha, Hunan 410011, China
| | - Zhenfei Fang
- Department of Cardiovascular Medicine, The Second Xiangya Hospital, Central South University, 139 Mid-Renmin Road, Changsha, Hunan 410011, China
| | - Qiming Liu
- Department of Cardiovascular Medicine, The Second Xiangya Hospital, Central South University, 139 Mid-Renmin Road, Changsha, Hunan 410011, China
| | - Xianling Liu
- Oncology Department, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Chunhong Hu
- Oncology Department, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Fang Ma
- Oncology Department, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Mu Zeng
- Radiology Department, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Zhi Liu
- Anesthesiology Department, Hunan Provincial People’s Hospital, Changsha, Hunan, China
| | - Lin Hu
- Department of Cardiovascular Medicine, The Second Xiangya Hospital, Central South University, 139 Mid-Renmin Road, Changsha, Hunan 410011, China
| | - Na Liu
- Department of Cardiovascular Medicine, The Second Xiangya Hospital, Central South University, 139 Mid-Renmin Road, Changsha, Hunan 410011, China
| | - Fan Xiang
- Department of Cardiovascular Medicine, The Second Xiangya Hospital, Central South University, 139 Mid-Renmin Road, Changsha, Hunan 410011, China
| | - Xinqun Hu
- Department of Cardiovascular Medicine, The Second Xiangya Hospital, Central South University, 139 Mid-Renmin Road, Changsha, Hunan 410011, China
| | - Lihong Huang
- Zhongshan Hospital Affiliated to Fudan University, Shanghai, China
| | - Shenghua Zhou
- Corresponding author. Tel: +86 731 85292012, Fax: +86 731 85292013,
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26
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Klett KC, Martin-Villa BC, Villarreal VS, Melemenidis S, Viswanathan V, Manjappa R, Ashraf MR, Soto L, Lau B, Dutt S, Rankin EB, Loo BW, Heilshorn SC. Human enteroids as a tool to study conventional and ultra-high dose rate radiation. Integr Biol (Camb) 2023; 15:zyad013. [PMID: 37874173 PMCID: PMC10594601 DOI: 10.1093/intbio/zyad013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2023] [Revised: 09/22/2023] [Accepted: 09/26/2023] [Indexed: 10/25/2023]
Abstract
Radiation therapy, one of the most effective therapies to treat cancer, is highly toxic to healthy tissue. The delivery of radiation at ultra-high dose rates, FLASH radiation therapy (FLASH), has been shown to maintain therapeutic anti-tumor efficacy while sparing normal tissues compared to conventional dose rate irradiation (CONV). Though promising, these studies have been limited mainly to murine models. Here, we leveraged enteroids, three-dimensional cell clusters that mimic the intestine, to study human-specific tissue response to radiation. We observed enteroids have a greater colony growth potential following FLASH compared with CONV. In addition, the enteroids that reformed following FLASH more frequently exhibited proper intestinal polarity. While we did not observe differences in enteroid damage across groups, we did see distinct transcriptomic changes. Specifically, the FLASH enteroids upregulated the expression of genes associated with the WNT-family, cell-cell adhesion, and hypoxia response. These studies validate human enteroids as a model to investigate FLASH and provide further evidence supporting clinical study of this therapy. Insight Box Promising work has been done to demonstrate the potential of ultra-high dose rate radiation (FLASH) to ablate cancerous tissue, while preserving healthy tissue. While encouraging, these findings have been primarily observed using pre-clinical murine and traditional two-dimensional cell culture. This study validates the use of human enteroids as a tool to investigate human-specific tissue response to FLASH. Specifically, the work described demonstrates the ability of enteroids to recapitulate previous in vivo findings, while also providing a lens through which to probe cellular and molecular-level responses to FLASH. The human enteroids described herein offer a powerful model that can be used to probe the underlying mechanisms of FLASH in future studies.
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Affiliation(s)
- Katarina C Klett
- Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA
| | | | - Victoria S Villarreal
- Department of Materials Science and Engineering, Stanford University, Stanford, CA, USA
| | - Stavros Melemenidis
- Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA, USA
| | - Vignesh Viswanathan
- Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA, USA
| | - Rakesh Manjappa
- Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA, USA
| | - M Ramish Ashraf
- Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA, USA
| | - Luis Soto
- Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA, USA
| | - Brianna Lau
- Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA, USA
| | - Suparna Dutt
- Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA, USA
| | - Erinn B Rankin
- Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA, USA
- Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, CA, USA
- Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA
| | - Billy W Loo
- Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA, USA
- Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA
| | - Sarah C Heilshorn
- Department of Materials Science and Engineering, Stanford University, Stanford, CA, USA
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Chalamgari A, Valle D, Palau Villarreal X, Foreman M, Liu A, Patel A, Dave A, Lucke-Wold B. Vertebral Primary Bone Lesions: Review of Management Options. Curr Oncol 2023; 30:3064-3078. [PMID: 36975445 PMCID: PMC10047554 DOI: 10.3390/curroncol30030232] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2023] [Revised: 02/26/2023] [Accepted: 03/03/2023] [Indexed: 03/08/2023] Open
Abstract
The assessment and treatment of vertebral primary bone lesions continue to pose a unique yet significant challenge. Indeed, there exists little in the literature in the way of compiling and overviewing the various types of vertebral lesions, which can often have complicated intervention strategies. Given the severe consequences of mismanaged vertebral bone tumors-including the extreme loss of motor function-it is clear that such an overview of spinal lesion care is needed. Thus, in the following paper, we aim to address the assessment of various vertebral primary bone lesions, outlining the relevant nonsurgical and surgical interventional methods. We describe examples of primary benign and malignant tumors, comparing and contrasting their differences. We also highlight emerging treatments and approaches for these tumors, like cryoablation and stereotactic body radiation therapy. Ultimately, we aim to emphasize the need for further guidelines in regard to correlating lesion type with proper therapy, underscoring the innate diversity of vertebral primary bone lesions in the literature.
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Affiliation(s)
| | | | | | | | | | | | | | - Brandon Lucke-Wold
- Department of Neurosurgery, University of Florida College of Medicine, Gainesville, FL 32601, USA
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28
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Stepanek CJ, Haynes JA, Fletcher S. Evaluation of a complementary metal oxide semiconductor detector as a tool for stereotactic body radiotherapy plan quality assurance. Phys Imaging Radiat Oncol 2023; 25:100418. [PMID: 36755894 PMCID: PMC9900433 DOI: 10.1016/j.phro.2023.100418] [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: 10/05/2022] [Revised: 01/19/2023] [Accepted: 01/20/2023] [Indexed: 01/26/2023] Open
Abstract
Background and purpose A sub-mm resolution Complementary Metal Oxide Semiconductor sensor has been developed for stereotactic radiotherapy quality assurance. Herein we evaluate its basic dosimetric performance and its application for linac C-arm stereotactic body radiotherapy (SBRT) plan quality assurance. Materials and methods The detector was integrated into its accompanying phantom or in Water Equivalent Plastic (WEP). The measurement reproducibility, stability, dose linearity and dependence on angularity, dose rate and field size were investigated. Clinical plan measurements were compared to our radiotherapy treatment planning system and radiochromic film. Sensitivity to introduced Multi Leaf Collimator (MLC) offsets was evaluated by simulating single MLC offsets in SBRT plans and comparing measurements to expected doses. Results Signal reproducibility was within ± 0.1 % and output calibration was stable over a 6 month period. Detector showed good linearity with dose (r2 = 1). Signal decreased by 5 % when dose rate was decreased from 1300 MU/min to 300 MU/min. Output factors agreed within 0.5 % of chamber measurements for 1x1 cm field sizes or greater. Angularity measurements showed good agreement with reference. For measurement of planned clinical doses, gamma pass-rates were 98.5 % ± 2.3 % (treatment planning system reference, 2 %/2mm) and 99.2 % ± 1.0 % (film reference, 2 %,2mm). The detector also showed sensitivity to errors of 1 mm offsets in MLC positioning. Conclusion The detector performed well when used for pre-treatment SBRT plan quality assurance, offering a good alternative to radiochromic film.
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29
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Pérez Haas Y, Ludwig R, Dal Bello R, Tanadini-Lang S, Unkelbach J. Adaptive fractionation at the MR-linac. Phys Med Biol 2023; 68. [PMID: 36596262 DOI: 10.1088/1361-6560/acafd4] [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: 06/22/2022] [Accepted: 01/03/2023] [Indexed: 01/04/2023]
Abstract
Objective. Fractionated radiotherapy typically delivers the same dose in each fraction. Adaptive fractionation (AF) is an approach to exploit inter-fraction motion by increasing the dose on days when the distance of tumor and dose-limiting organs at risk (OAR) is large and decreasing the dose on unfavorable days. We develop an AF algorithm and evaluate the concept for patients with abdominal tumors previously treated at the MR-linac in 5 fractions.Approach. Given daily adapted treatment plans, inter-fractional changes are quantified by sparing factorsδtdefined as the OAR-to-tumor dose ratio. The key problem of AF is to decide on the dose to deliver in fractiont, givenδtand the dose delivered in previous fractions, but not knowing futureδts. Optimal doses that maximize the expected biologically effective dose in the tumor (BED10) while staying below a maximum OAR BED3constraint are computed using dynamic programming, assuming a normal distribution overδwith mean and variance estimated from previously observed patient-specificδts. The algorithm is evaluated for 16 MR-linac patients in whom tumor dose was compromised due to proximity of bowel, stomach, or duodenum.Main Results. In 14 out of the 16 patients, AF increased the tumor BED10compared to the reference treatment that delivers the same OAR dose in each fraction. However, in 11 of these 14 patients, the increase in BED10was below 1 Gy. Two patients with large sparing factor variation had a benefit of more than 10 Gy BED10increase. For one patient, AF led to a 5 Gy BED10decrease due to an unfavorable order of sparing factors.Significance. On average, AF provided only a small increase in tumor BED. However, AF may yield substantial benefits for individual patients with large variations in the geometry.
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Affiliation(s)
- Y Pérez Haas
- Department of Radiation Oncology, University Hospital of Zurich, Zurich, Switzerland
| | - R Ludwig
- Department of Radiation Oncology, University Hospital of Zurich, Zurich, Switzerland
| | - R Dal Bello
- Department of Radiation Oncology, University Hospital of Zurich, Zurich, Switzerland
| | - S Tanadini-Lang
- Department of Radiation Oncology, University Hospital of Zurich, Zurich, Switzerland
| | - J Unkelbach
- Department of Radiation Oncology, University Hospital of Zurich, Zurich, Switzerland
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Sato A, Kraynak J, Marciscano AE, Galluzzi L. Radiation therapy: An old dog learning new tricks. Methods Cell Biol 2023; 174:xv-xxv. [PMID: 37039770 DOI: 10.1016/s0091-679x(23)00036-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
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Sato A, Kraynak J, Marciscano AE, Galluzzi L. Radiation therapy: An old dog learning new tricks. Methods Cell Biol 2023; 180:xv-xxv. [PMID: 37890936 DOI: 10.1016/s0091-679x(23)00166-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/29/2023]
Affiliation(s)
- Ai Sato
- Department of Radiation Oncology, Weill Cornell Medical College, New York, NY, United States
| | - Jeffrey Kraynak
- Department of Radiation Oncology, Weill Cornell Medical College, New York, NY, United States
| | - Ariel E Marciscano
- Department of Radiation Oncology, Weill Cornell Medical College, New York, NY, United States
| | - Lorenzo Galluzzi
- Department of Radiation Oncology, Weill Cornell Medical College, New York, NY, United States; Sandra and Edward Meyer Cancer Center, New York, NY, United States; Caryl and Israel Englander Institute for Precision Medicine, New York, NY, United States.
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Tang C, Gong C, Liu B, Guo H, Dai Z, Yuan J, Wang X, Zhang Y. Feasibility and dosimetric evaluation of single- and multi-isocentre stereotactic body radiation therapy for multiple liver metastases. Front Oncol 2023; 13:1144784. [PMID: 37188200 PMCID: PMC10175834 DOI: 10.3389/fonc.2023.1144784] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2023] [Accepted: 04/13/2023] [Indexed: 05/17/2023] Open
Abstract
Objectives Single-isocentre volumetric-modulated arc therapy (VMAT) stereotactic body radiation therapy (SBRT) improves treatment efficiency and patient compliance for patients with multiple liver metastases (MLM). However, the potential increase in dose spillage to normal liver tissue using a single-isocentre technique has not yet been studied. We comprehensively evaluated the quality of single- and multi-isocentre VMAT-SBRT for MLM and propose a RapidPlan-based automatic planning (AP) approach for MLM SBRT. Methods A total of 30 patients with MLM (two or three lesions) were selected for this retrospective study. We manually replanned all patients treated with MLM SBRT by using the single-isocentre (MUS) and multi-isocentre (MUM) techniques. Then, we randomly selected 20 MUS and MUM plans for training to generate the single-isocentre RapidPlan model (RPS) and the multi-isocentre RapidPlan model (RPM). Finally, we used data from the remaining 10 patients to validate RPS and RPM. Results Compared with MUS, MUM reduced the mean dose delivered to the right kidney by 0.3 Gy. The mean liver dose (MLD) was 2.3 Gy higher for MUS compared with MUM. However, the monitor units, delivery time, and V20Gy of normal liver (liver-gross tumour volume) for MUM were significantly higher than for MUS. Based on validation, RPS and RPM slightly improved the MLD, V20Gy, normal tissue complications, and dose sparing to the right and left kidneys and spinal cord compared with manual plans (MUS vs RPS and MUM vs RPM), but RPS and RPM significantly increased monitor units and delivery time. Conclusions The single-isocentre VMAT-SBRT approach could be used for MLM to reduce treatment time and patient comfort at the cost of a small increase in the MLD. Compared with the manual plans, RapidPlan-based plans, especially RPS, have slightly improved quality.
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Affiliation(s)
- Chunbo Tang
- Department of Oncology, First Affiliated Hospital of Gannan Medical University, Ganzhou, China
| | - Changfei Gong
- Department of Radiation Oncology, Jiangxi Cancer Hospital, Nanchang, China
- *Correspondence: Changfei Gong, ; Yun Zhang,
| | - Biaoshui Liu
- Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Hailiang Guo
- Department of Oncology, First Affiliated Hospital of Gannan Medical University, Ganzhou, China
| | - Zhongyang Dai
- Department of Oncology, First Affiliated Hospital of Gannan Medical University, Ganzhou, China
| | - Jun Yuan
- Department of Oncology, First Affiliated Hospital of Gannan Medical University, Ganzhou, China
| | - Xiaoping Wang
- Department of Radiation Oncology, Jiangxi Cancer Hospital, Nanchang, China
| | - Yun Zhang
- Department of Radiation Oncology, Jiangxi Cancer Hospital, Nanchang, China
- *Correspondence: Changfei Gong, ; Yun Zhang,
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Du Y, Zheng Y, Yu K, Zhan C, Qiao T. Genome-wide analyses of lung cancer after single high-dose radiation at five time points (2, 6, 12, 24, and 48 h). Front Genet 2023; 14:1126236. [PMID: 36936419 PMCID: PMC10020487 DOI: 10.3389/fgene.2023.1126236] [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: 12/17/2022] [Accepted: 02/13/2023] [Indexed: 03/06/2023] Open
Abstract
Background: An increasing number of clinicians are experimenting with high-dose radiation. This study focuses on the genomic effects of high-dose single-shot radiotherapy and aims to provide a dynamic map for non-small cell lung cancer (NSCLC). Methods: We used whole-transcriptome sequencing to understand the evolution at molecular levels in A549 and H1299 exposed to 10 Gy X-rays at different times (2, 6, 12, 24, and 48 h) in comparison with the no radiation group. Ingenuity pathway analysis, ceRNA analysis, enrichment analysis, and cell cycle experiments are performed for molecular analyses and function analyses. Results: Whole-transcriptome sequencing of NSCLC showed a significant dynamic change after radiotherapy within 48 h. MiR-219-1-3p and miR-221-3p, miR-503-5p, hsa-miR-455-5p, hsa-miR-29-3p, and hsa-miR-339-5p were in the core of the ceRNA related to time change. GO and KEGG analyses of the top 30 mRNA included DNA repair, autophagy, apoptosis, and ferroptosis pathways. Regulation of the cell cycle-related transcription factor E2F1 might have a key role in the early stage of radiotherapy (2.6 h) and in the later stage of autophagy (24 and 48 h). Functions involving different genes/proteins over multiple periods implied a dose of 10 Gy was related to the kidney and liver pathway. Radiation-induced cell cycle arrest at the G2/M phase was evident at 24 h. We also observed the increased expression of CCNB1 at 24 h in PCR and WB experiments. Conclusion: Our transcriptomic and experimental analyses showed a dynamic change after radiation therapy in 48 h and highlighted the key molecules and pathways in NSCLC after high-dose single-shot radiotherapy.
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Affiliation(s)
- Yajing Du
- Center for Tumor Diagnosis and Therapy, Jinshan Hospital, Fudan University, Shanghai, China
| | | | - Kaiwen Yu
- Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China
| | - Cheng Zhan
- Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Tiankui Qiao
- Center for Tumor Diagnosis and Therapy, Jinshan Hospital, Fudan University, Shanghai, China
- *Correspondence: Tiankui Qiao,
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Wang Y, Wang Y, Yu J, Meng X. The treatment in patients with unresectable locally advanced non-small cell lung cancer: Explorations on hot issues. Cancer Lett 2022; 551:215947. [PMID: 36265654 DOI: 10.1016/j.canlet.2022.215947] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2022] [Revised: 09/28/2022] [Accepted: 10/03/2022] [Indexed: 11/02/2022]
Abstract
The treatment efficacy for patients with unresectable, locally advanced non-small-cell lung cancer (LA-NSCLC) stagnated for a long time until the advent of immunotherapy. Immune checkpoint inhibitors, particularly programmed cell death protein 1/programmed death-ligand 1 inhibitors, have thrived, reshaping the treatment landscape for patients with lung cancer. Based on the results of the PACIFIC trial, concurrent chemoradiotherapy followed by durvalumab has become the standard of care for patients with unresectable LA-NSCLC; however, numerous issues are yet to be resolved. Currently, several clinical trials are exploring an optimal treatment paradigm, and we have summarized them for comparison to eliminate barriers. In addition, we discuss better predictive biomarkers, therapeutic options for specific populations, and other challenges to identify directions for future research design.
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Affiliation(s)
- Yimeng Wang
- Department of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Yao Wang
- Department of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Jinming Yu
- Department of Radiation Oncology and Shandong Provincial Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China; Research Unit of Radiation Oncology, Chinese Academy of Medical Sciences, Jinan, Shandong, China.
| | - Xiangjiao Meng
- Department of Radiation Oncology and Shandong Provincial Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China; Research Unit of Radiation Oncology, Chinese Academy of Medical Sciences, Jinan, Shandong, China.
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Shishido K, Reinders A, Asuthkar S. Epigenetic regulation of radioresistance: insights from preclinical and clinical studies. Expert Opin Investig Drugs 2022; 31:1359-1375. [PMID: 36524403 DOI: 10.1080/13543784.2022.2158810] [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: 12/23/2022]
Abstract
INTRODUCTION Oftentimes, radiation therapy (RT) is ineffective due to the development of radioresistance (RR). However, studies have shown that targeting epigenetic modifiers to enhance radiosensitivity represents a promising direction of clinical investigation. AREAS COVERED This review discusses the mechanisms by which epigenetic modifiers alter radiosensitivity through dysregulation of MAPK-ERK and AKT-mTOR signaling. Finally, we discuss the clinical directions for targeting epigenetic modifiers and current radiology techniques used in the clinic. METHODOLOGY We searched PubMed and ScienceDirect databases from April 4th, 2022 to October 18th, 2022. We examined 226 papers related to radioresistance, epigenetics, MAPK, and PI3K/AKT/mTOR signaling. 194 papers were selected for this review. Keywords used for this search include, 'radioresistance,' 'radiosensitivity,' 'radiation,' 'radiotherapy,' 'particle radiation,' 'photon radiation,' 'epigenetic modifiers,' 'MAPK,' 'AKT,' 'mTOR,' 'cancer,' and 'PI3K.' We examined 41 papers related to clinical trials on the aforementioned topics. Outcomes of interest were safety, overall survival (OS), dose-limiting toxicities (DLT), progression-free survival (PFS), and maximum tolerated dose (MTD). EXPERT OPINION Current studies focusing on epigenetic mechanisms of RR strongly support the use of targeting epigenetic modifiers as adjuvants to standard cancer therapies. To further the success of such treatments and their clinical benefit , both preclinical and clinical studies are needed to broaden the scope of known radioresistant mechanisms.
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Affiliation(s)
- Katherine Shishido
- Department of Cancer Biology and Pharmacology and Department of Pediatrics, University of Illinois College of Medicine Peoria, Peoria, IL, United States of America
| | - Alexis Reinders
- Department of Cancer Biology and Pharmacology and Department of Pediatrics, University of Illinois College of Medicine Peoria, Peoria, IL, United States of America
| | - Swapna Asuthkar
- Department of Cancer Biology and Pharmacology and Department of Pediatrics, University of Illinois College of Medicine Peoria, Peoria, IL, United States of America
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Frank AJ, Dagogo-Jack I, Dobre IA, Tait S, Schumacher L, Fintelmann FJ, Fingerman LM, Keane FK, Montesi SB. Management of Lung Cancer in the Patient with Interstitial Lung Disease. Oncologist 2022; 28:12-22. [PMID: 36426803 PMCID: PMC9847545 DOI: 10.1093/oncolo/oyac226] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2022] [Accepted: 09/23/2022] [Indexed: 11/26/2022] Open
Abstract
Patients with interstitial lung disease (ILD), especially those with pulmonary fibrosis, are at increased risk of developing lung cancer. Management of lung cancer in patients with ILD is particularly challenging. Diagnosis can be complicated by difficulty differentiating lung nodules from areas of focal fibrosis, and percutaneous biopsy approaches confer an increased risk of complications in those with pulmonary fibrosis. Lung cancer treatment in these patients pose several specific considerations. The degree of lung function impairment may preclude lobectomy or surgical resection of any type. Surgical resection can trigger an acute exacerbation of the underlying ILD. The presence of ILD confers an increased risk of pneumonitis with radiotherapy, and many of the systemic therapies also carry an increased risk of pneumonitis in this population. The safety of immunotherapy in the setting of ILD remains to be fully elucidated and concerns remain as to triggering pneumonitis. The purpose of this review is to summarize the evidence regarding consideration for tissue diagnosis, chemotherapy and immunotherapy, radiotherapy, and surgery, in this patient population and discuss emerging areas of research. We also propose a multidisciplinary approach and practical considerations for monitoring for ILD progression during lung cancer treatment.
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Affiliation(s)
| | | | - Ioana A Dobre
- Queen’s University School of Medicine, Kingston, ON, Canada
| | - Sarah Tait
- Department of Medicine, Massachusetts General Hospital, Boston, MA, USA
| | - Lana Schumacher
- Department of Surgery, Massachusetts General Hospital, Boston, MA, USA
| | - Florian J Fintelmann
- Department of Radiology, Division of Thoracic Imaging and Intervention, Massachusetts General Hospital, Boston, MA, USA
| | - Leah M Fingerman
- Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital, Boston, MA, USA
| | - Florence K Keane
- Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA, USA
| | - Sydney B Montesi
- Corresponding author: Sydney B. Montesi, MD, Massachusetts General Hospital, 55 Fruit Street, BUL-148, Boston, MA 02114, USA. Tel: +1 617 724 4030;
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Sun X, Dai Z, Xu M, Guo X, Su H, Li Y. Quantifying 6D tumor motion and calculating PTV margins during liver stereotactic radiotherapy with fiducial tracking. Front Oncol 2022; 12:1021119. [DOI: 10.3389/fonc.2022.1021119] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2022] [Accepted: 10/18/2022] [Indexed: 11/18/2022] Open
Abstract
ObjectiveOur study aims to estimate intra-fraction six-dimensional (6D) tumor motion with rotational correction and the related correlations between motions of different degrees of freedom (DoF), as well as quantify sufficient anisotropic clinical target volume (CTV) to planning target volume (PTV) margins during stereotactic body radiotherapy (SBRT) of liver cancer with fiducial tracking technique.MethodsA cohort of 12 patients who were implanted with 3 or 4 golden markers were included in this study, and 495 orthogonal kilovoltage (kV) pairs of images acquired during the first fraction were used to extract the spacial position of each golden marker. Translational and rotational motions of tumor were calculated based on the marker coordinates by using an iterative closest point (ICP) algorithm. Moreover, the Pearson product-moment correlation coefficients (r) were applied to quantify the correlations between motions with different degrees of freedom (DoFs). The population mean displacement (MP¯), systematic error (Σ) and random error (σ) were obtained to calculate PTV margins based on published recipes.ResultsThe mean translational variability of tumors were 0.56, 1.24 and 3.38 mm in the left-right (LR, X), anterior-posterior (AP, Y), and superior-inferior (SI, Z) directions, respectively. The average rotational angles θX , θY and θZ around the three coordinate axes were 0.88, 1.24 and 1.12, respectively. (|r|>0.4) was obtainted between Y -Z , Y - θZ , Z -θZ and θX - θY . The PTV margins calculated based on 13 published recipes in X, Y, and Z directions were 1.08, 2.26 and 5.42 mm, and the 95% confidence interval (CI) of them were (0.88,1.28), (1.99,2.53) and (4.78,6.05), respectively.ConclusionsThe maximum translational motion was in SI direction, and the largest correlation coefficient of Y-Z was obtained. We recommend margins of 2, 3 and 7 mm in LR, AP and SI directions, respectively.
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Barcellos-Hoff MH. The radiobiology of TGFβ. Semin Cancer Biol 2022; 86:857-867. [PMID: 35122974 DOI: 10.1016/j.semcancer.2022.02.001] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2021] [Revised: 01/31/2022] [Accepted: 02/01/2022] [Indexed: 01/27/2023]
Abstract
Ionizing radiation is a pillar of cancer therapy that is deployed in more than half of all malignancies. The therapeutic effect of radiation is attributed to induction of DNA damage that kills cancers cells, but radiation also affects signaling that alters the composition of the tumor microenvironment by activating transforming growth factor β (TGFβ). TGFβ is a ubiquitously expressed cytokine that acts as biological lynchpin to orchestrate phenotypes, the stroma, and immunity in normal tissue; these activities are subverted in cancer to promote malignancy, a permissive tumor microenvironment and immune evasion. The radiobiology of TGFβ unites targets at the forefront of oncology-the DNA damage response and immunotherapy. The cancer cell intrinsic and extrinsic network of TGFβ responses in the irradiated tumor form a barrier to both genotoxic treatments and immunotherapy response. Here, we focus on the mechanisms by which radiation induces TGFβ activation, how TGFβ regulates DNA repair, and the dynamic regulation of the tumor immune microenvironment that together oppose effective cancer therapy. Strategies to inhibit TGFβ exploit fundamental radiobiology that may be the missing link to deploying TGFβ inhibitors for optimal patient benefit from cancer treatment.
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Affiliation(s)
- Mary Helen Barcellos-Hoff
- Department of Radiation Oncology and Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.
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Biau J, Lopez L, Thivat E, Casile M, Millardet C, Saroul N, Pham-Dang N, Molnar I, Bourhis J, Lapeyre M. Postoperative SBRT in the Treatment of Early-Stage Oropharyngeal and Oral Cavity Cancers with High-Risk Margins: a dosimetric comparison of volumetric modulated arc therapy with or without non-coplanar arcs and acute toxicity outcomes from the STEREOPOSTOP GORTEC 2017-03 phase 2 trial. Clin Transl Radiat Oncol 2022; 38:169-174. [DOI: 10.1016/j.ctro.2022.11.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2022] [Revised: 11/08/2022] [Accepted: 11/10/2022] [Indexed: 11/16/2022] Open
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Vozenin MC, Bourhis J, Durante M. Towards clinical translation of FLASH radiotherapy. Nat Rev Clin Oncol 2022; 19:791-803. [DOI: 10.1038/s41571-022-00697-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/30/2022] [Indexed: 11/09/2022]
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Kirste S, Rühle A, Zschiedrich S, Schultze-Seemann W, Jilg CA, Neumann-Haefelin E, Lo SS, Grosu AL, Kim E. Stereotactic Body Radiotherapy for Renal Cell Carcinoma in Patients with Von Hippel-Lindau Disease-Results of a Prospective Trial. Cancers (Basel) 2022; 14:5069. [PMID: 36291853 PMCID: PMC9599838 DOI: 10.3390/cancers14205069] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Revised: 10/04/2022] [Accepted: 10/12/2022] [Indexed: 11/18/2022] Open
Abstract
Von Hippel-Lindau disease (VHL) is a hereditary disorder associated with malignant tumors including clear cell renal cell carcinoma (ccRCC). Partial nephrectomy is complicated by multilocular tumor occurrence and a high recurrence rate. The aim of this study was to evaluate the potential of stereotactic body radiotherapy (SBRT) as an alternative treatment approach in VHL patients with multiple ccRCC. Patients with VHL and a diagnosis of ccRCC were enrolled. SBRT was conducted using five fractions of 10 Gy or eight fractions of 7.5 Gy. The primary endpoint was local control (LC). Secondary endpoints included alteration of renal function and adverse events. Seven patients with a total of eight treated lesions were enrolled. Median age was 44 years. Five patients exhibited multiple bilateral kidney cysts in addition to ccRCC. Three patients underwent at least one partial nephrectomy in the past. After a median follow-up of 43 months, 2-year LC was 100%, while 2-year CSS, 2-year PFS and 2-year OS was 100%, 85.7% and 85.7%, respectively. SBRT was very well tolerated with no acute or chronic toxicities grade ≥ 2. Mean estimated glomerular filtration rate (eGFR) at baseline was 83.7 ± 13.0 mL/min/1.73 m2, which decreased to 76.6 ± 8.0 mL/min/1.73 m2 after 1 year. Although the sample size was small, SBRT resulted in an excellent LC rate and was very well tolerated with preservation of kidney function in patients with multiple renal lesions and cysts.
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Affiliation(s)
- Simon Kirste
- Department of Radiation Oncology, Medical Center—University of Freiburg, Faculty of Medicine, 79106 Freiburg, Germany
- German Cancer Consortium (DKTK) Partner Site Freiburg, German Cancer Research Center (dkfz), 69120 Heidelberg, Germany
| | - Alexander Rühle
- Department of Radiation Oncology, Medical Center—University of Freiburg, Faculty of Medicine, 79106 Freiburg, Germany
- German Cancer Consortium (DKTK) Partner Site Freiburg, German Cancer Research Center (dkfz), 69120 Heidelberg, Germany
| | - Stefan Zschiedrich
- Renal Division, Department of Internal Medicine, Bürgerspital Solothurn, 4500 Solothurn, Switzerland
- Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany
| | - Wolfgang Schultze-Seemann
- Department of Urology, Medical Center—University of Freiburg, Faculty of Medicine, 79106 Freiburg, Germany
| | - Cordula A. Jilg
- Department of Urology, Medical Center—University of Freiburg, Faculty of Medicine, 79106 Freiburg, Germany
| | - Elke Neumann-Haefelin
- Renal Division, Department of Medicine, Medical Center—University of Freiburg, Faculty of Medicine, 79106 Freiburg, Germany
| | - Simon S. Lo
- Department of Radiation Oncology, University of Washington School of Medicine, Seattle, WA 98195, USA
| | - Anca-Ligia Grosu
- Department of Radiation Oncology, Medical Center—University of Freiburg, Faculty of Medicine, 79106 Freiburg, Germany
- German Cancer Consortium (DKTK) Partner Site Freiburg, German Cancer Research Center (dkfz), 69120 Heidelberg, Germany
| | - Emily Kim
- Department of Radiation Oncology, Medical Center—University of Freiburg, Faculty of Medicine, 79106 Freiburg, Germany
- German Cancer Consortium (DKTK) Partner Site Freiburg, German Cancer Research Center (dkfz), 69120 Heidelberg, Germany
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Pirrone G, Matrone F, Chiovati P, Manente S, Drigo A, Donofrio A, Cappelletto C, Borsatti E, Dassie A, Bortolus R, Avanzo M. Predicting Local Failure after Partial Prostate Re-Irradiation Using a Dosiomic-Based Machine Learning Model. J Pers Med 2022; 12:1491. [PMID: 36143276 PMCID: PMC9505150 DOI: 10.3390/jpm12091491] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2022] [Revised: 09/02/2022] [Accepted: 09/05/2022] [Indexed: 12/22/2022] Open
Abstract
The aim of this study is to predict local failure after partial prostate re-irradiation for the treatment of isolated locally recurrent prostate cancer by using a machine learning classifier based on radiomic features from pre-treatment computed tomography (CT), positron-emission tomography (PET) and biological effective dose distribution (BED) of the radiotherapy plan. The analysis was conducted on a monocentric dataset of 43 patients with evidence of isolated intraprostatic recurrence of prostate cancer after primary external beam radiotherapy. All patients received partial prostate re-irradiation delivered by volumetric modulated arc therapy. The gross tumor volume (GTV) of each patient was manually contoured from planning CT, choline-PET and dose maps. An ensemble machine learning pipeline including unbalanced data correction and feature selection was trained using the radiomic and dosiomic features as input for predicting occurrence of local failure. The model performance was assessed using sensitivity, specificity, accuracy and area under receiver operating characteristic curves of the score function in 10-fold cross validation repeated 100 times. Local failure was observed in 13 patients (30%), with a median time to recurrence of 36.7 months (range = 6.1-102.4 months). A four variables ensemble machine learning model resulted in accuracy of 0.62 and AUC 0.65. According to our results, a dosiomic machine learning classifier can predict local failure after partial prostate re-irradiation.
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Affiliation(s)
- Giovanni Pirrone
- Medical Physics Department, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, 33081 Aviano, Italy
| | - Fabio Matrone
- Radiation Oncology Department, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, 33081 Aviano, Italy
| | - Paola Chiovati
- Medical Physics Department, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, 33081 Aviano, Italy
| | - Stefania Manente
- Nuclear Medicine Department, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, 33081 Aviano, Italy
| | - Annalisa Drigo
- Medical Physics Department, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, 33081 Aviano, Italy
| | - Alessandra Donofrio
- Radiation Oncology Department, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, 33081 Aviano, Italy
| | - Cristina Cappelletto
- Medical Physics Department, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, 33081 Aviano, Italy
| | - Eugenio Borsatti
- Nuclear Medicine Department, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, 33081 Aviano, Italy
| | - Andrea Dassie
- Medical Physics Department, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, 33081 Aviano, Italy
| | - Roberto Bortolus
- Radiation Oncology Department, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, 33081 Aviano, Italy
| | - Michele Avanzo
- Medical Physics Department, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, 33081 Aviano, Italy
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Binary dose level classification of tumour microvascular response to radiotherapy using artificial intelligence analysis of optical coherence tomography images. Sci Rep 2022; 12:13995. [PMID: 35978040 PMCID: PMC9385745 DOI: 10.1038/s41598-022-18393-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2022] [Accepted: 08/10/2022] [Indexed: 12/26/2022] Open
Abstract
The dominant consequence of irradiating biological systems is cellular damage, yet microvascular damage begins to assume an increasingly important role as the radiation dose levels increase. This is currently becoming more relevant in radiation medicine with its pivot towards higher-dose-per-fraction/fewer fractions treatment paradigm (e.g., stereotactic body radiotherapy (SBRT)). We have thus developed a 3D preclinical imaging platform based on speckle-variance optical coherence tomography (svOCT) for longitudinal monitoring of tumour microvascular radiation responses in vivo. Here we present an artificial intelligence (AI) approach to analyze the resultant microvascular data. In this initial study, we show that AI can successfully classify SBRT-relevant clinical radiation dose levels at multiple timepoints (t = 2–4 weeks) following irradiation (10 Gy and 30 Gy cohorts) based on induced changes in the detected microvascular networks. Practicality of the obtained results, challenges associated with modest number of animals, their successful mitigation via augmented data approaches, and advantages of using 3D deep learning methodologies, are discussed. Extension of this encouraging initial study to longitudinal AI-based time-series analysis for treatment outcome predictions at finer dose level gradations is envisioned.
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Bahig H, Huang SH, O’Sullivan B. Oligometastatic Head and Neck Cancer: Challenges and Perspectives. Cancers (Basel) 2022; 14:cancers14163894. [PMID: 36010888 PMCID: PMC9405984 DOI: 10.3390/cancers14163894] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2022] [Revised: 08/09/2022] [Accepted: 08/10/2022] [Indexed: 11/17/2022] Open
Abstract
Simple Summary Oligometastasis represents a disease state and an opportunity for cure when metastases emerge. Emerging evidence supports that most head and neck cancer patients with oligometastatic disease are likely to benefit from curative intent local ablative therapy if appropriate selection criteria are applied. Biomarkers to predict development of oligometastasis, as well as to identify which patients could benefit from a radical intent approach, are under investigation. This review summarizes recent knowledge about the characteristics, investigational efforts, and evidence for local ablation regarding oligometastasis in head and neck cancer. We also describe the challenges and opportunities in patient selection and discuss the role of radiotherapy and immunotherapy combinations to enhance anti-tumor immunity. Abstract A minority of patients with metastatic head and neck squamous cell carcinoma (HNSCC) present with oligometastatic disease. Oligometastasis not only reflects a disease state, but might also present an opportunity for cure in the metastatic setting. Radical ablation of all oligometastatic sites may confer prolonged survival and possibly achieve cure in some patients. However, substantial debate remains about whether patients with oligometastatic disease could benefit from curative intent therapy or whether aggressive treatments expose some patients to futile toxicity. Optimal selection of patients, carefully balancing the currently known prognostic factors against the risks of toxicity is critical. Emerging evidence suggests that patients with a limited burden of disease, viral-related pharyngeal cancer, metachronous metastasis and lung-only metastasis may benefit most from this approach. Efforts are underway to identify biomarkers that can detect oligometastasis and better select patients who would derive the maximum benefit from an aggressive radical approach. The combination of radiotherapy and immunotherapy promises to enhance the anti-tumoral immune response and help overcome resistance. However, optimization of management algorithms, including patient selection, radiation dose and sequencing, will be critical in upcoming clinical trials. This review summarizes recent knowledge about the characteristics and investigational efforts regarding oligometastasis in HNSCC.
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Affiliation(s)
- Houda Bahig
- Department of Radiation Oncology, University of Montreal, Montreal, QC H2X 3E4, Canada
| | - Shao Hui Huang
- Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON M5G 2M9, Canada
- Department of Otolaryngology-Head and Neck Surgery, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON M5G 2M9, Canada
| | - Brian O’Sullivan
- Department of Radiation Oncology, University of Montreal, Montreal, QC H2X 3E4, Canada
- Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON M5G 2M9, Canada
- Department of Otolaryngology-Head and Neck Surgery, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON M5G 2M9, Canada
- Correspondence:
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Chen D, Zhao M, Xiang X, Liang J. Percutaneous local tumor ablation vs. stereotactic body radiotherapy for early-stage non-small cell lung cancer: a systematic review and meta-analysis. Chin Med J (Engl) 2022; 135:00029330-990000000-00031. [PMID: 35830244 PMCID: PMC9532043 DOI: 10.1097/cm9.0000000000002131] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2021] [Indexed: 11/26/2022] Open
Abstract
BACKGROUND Percutaneous local tumor ablation (LTA) and stereotactic body radiotherapy (SBRT) have been regarded as viable treatments for early-stage lung cancer patients. The purpose of this study was to compare the efficacy and safety of LTA with SBRT for early-stage non-small cell lung cancer (NSCLC). METHODS PubMed, Embase, Cochrane library, Ovid, Google scholar, CNKI, and CBMdisc were searched to identify potential eligible studies comparing the efficacy and safety of LTA with SBRT for early-stage NSCLC published between January 1, 1991, and May 31, 2021. Hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were applied to estimate the effect size for overall survival (OS), progression-free survival (PFS), locoregional progression (LP), and adverse events. RESULTS Five studies with 22,231 patients were enrolled, including 1443 patients in the LTA group and 20,788 patients in the SBRT group. The results showed that SBRT was not superior to LTA for OS (HR = 1.03, 95% CI: 0.87-1.22, P = 0.71). Similar results were observed for PFS (HR = 1.09, 95% CI: 0.71-1.67, P = 0.71) and LP (HR = 0.66, 95% CI: 0.25-1.77, P = 0.70). Subgroup analysis showed that the pooled HR for OS favored SBRT in patients with tumors sized >2 cm (HR = 1.32, 95% CI: 1.14-1.53, P = 0.0003), whereas there was no significant difference in patients with tumors sized ≤2 cm (HR = 0.93, 95% CI: 0.64-1.35, P = 0.70). Moreover, no significant differences were observed for the incidence of severe adverse events (≥grade 3) (OR = 1.95, 95% CI: 0.63-6.07, P = 0.25) between the LTA group and SBRT group. CONCLUSIONS Compared with SBRT, LTA appears to have similar OS, PFS, and LP. However, for tumors >2 cm, SBRT is superior to LTA in OS. Prospective randomized controlled trials are required to determine such findings. INPLASY REGISTRATION NUMBER INPLASY202160099.
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Affiliation(s)
- Dongjie Chen
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, Guangdong 518172, China
| | - Man Zhao
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, Guangdong 518172, China
| | - Xiaoyong Xiang
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, Guangdong 518172, China
| | - Jun Liang
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, Guangdong 518172, China
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Cheng K, Wang Y, Chen Y, Zhu J, Qi X, Wang Y, Zou Y, Lu Q, Li Z. Multisite Radiotherapy Combined With Tislelizumab for Metastatic Castration-Resistant Prostate Cancer With Second-Line and Above Therapy Failure: Study Protocol for an Open-Label, Single-Arm, Phase Ib/II Study. Front Oncol 2022; 12:888707. [PMID: 35875078 PMCID: PMC9300836 DOI: 10.3389/fonc.2022.888707] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2022] [Accepted: 06/10/2022] [Indexed: 11/24/2022] Open
Abstract
Background Tislelizumab combined with radiotherapy as a salvage treatment for patients with end-stage metastatic castration-resistant prostate cancer (mCRPC) is not reported. This study aimed to describe a protocol to evaluate the safety and efficacy of multisite radiotherapy combined with tislelizumab as a salvage therapy for mCRPC in patients who had at least one second-line treatment failure. Methods The study included patients with mCRPC who had at least one lesion suitable for radiotherapy and failed androgen deprivation therapy (ADT), followed by at least one novel second-line endocrine therapy. All patients received tislelizumab monotherapy induction therapy for two cycles, then combined with multisite radiotherapy for one cycle, followed by tislelizumab maintenance therapy, until either disease progressed or the patient developed unacceptable toxicity. Radiation methods and lesions were individually selected according to the specified protocol. Primary endpoints included safety and objective response rate. Secondary endpoints included prostate-specific antigen (PSA) response rate, disease control rate, overall survival, radiographic progression-free survival (rPFS), and biochemical progression-free survival (bPFS). Furthermore, the exploratory endpoints included the identification of the predictive biomarkers and exploration of the correlation between biomarkers and the tumor response to the combined regimen. Discussion This study included three treatment stages to evaluate the efficacy of immunotherapy and the combination of immunotherapy and radiotherapy for patients with mCRPC who have had at least second-line treatment failure. Additionally, radiation-related and immune-related early and late toxicities were determined, respectively. Furthermore, the study also aimed to identify the predictive biomarkers associated with immunotherapy for treating mCRPC. Trial Registration https://www.chictr.org.cn/showproj.aspx?proj=126359, identifier ChiCTR2100046212.
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Affiliation(s)
- Ke Cheng
- Department of Abdominal Oncology, West China Hospital, Sichuan University, Chengdu, China
| | - Yuqing Wang
- State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
- West China School of Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Ye Chen
- Department of Abdominal Oncology, West China Hospital, Sichuan University, Chengdu, China
| | - Jingjie Zhu
- West China School of Public Health, Sichuan University, Chengdu, China
| | - Xiaohui Qi
- Laboratory of Clinical Pharmacy and Adverse Drug Reaction, West China Hospital, Sichuan University, Chengdu, China
| | - Yachen Wang
- West China School of Public Health, Sichuan University, Chengdu, China
| | - Yanqiu Zou
- West China School of Public Health, Sichuan University, Chengdu, China
| | - Qiuhan Lu
- West China School of Public Health, Sichuan University, Chengdu, China
| | - Zhiping Li
- Department of Radiotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, China
- *Correspondence: Zhiping Li,
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Hoover AR, Liu K, DeVette CI, Krawic JR, Medcalf AD, West CL, Hode T, Lam SSK, Welm AL, Sun XH, Hildebrand WH, Chen WR. Single-cell RNA sequencing reveals localized tumour ablation and intratumoural immunostimulant delivery potentiate T cell mediated tumour killing. Clin Transl Med 2022; 12:e937. [PMID: 35808806 PMCID: PMC9270578 DOI: 10.1002/ctm2.937] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2022] [Revised: 05/27/2022] [Accepted: 06/05/2022] [Indexed: 12/16/2022] Open
Abstract
Background Metastatic breast cancer poses great challenge in cancer treatment. N‐dihydrogalactochitosan (GC) is a novel immunoadjuvant that stimulates systemic immune responses when administered intratumourally following local tumour ablation. A combination of photothermal therapy (PTT) and GC, referred to as localized ablative immunotherapy (LAIT), extended animal survival and generates an activated B cell phenotype in MMTV‐PyMT mouse mammary tumour microenvironment (TME). However, how T cell populations respond to LAIT remains to be elucidated. Methods Using depletion antibodies, we studied the contributions of CD8+ and CD4+ T cells to the therapeutic effect of LAIT. Using single‐cell RNA‐sequencing (scRNAseq), we analysed tumour‐infiltrating T cell heterogeneity and dissected their transcriptomes upon treatments of PTT, GC, and LAIT (PTT+GC). Results Loss of CD8+ T cells after LAIT abrogated the therapeutic benefits of LAIT. Ten days after treatment, proportions of CD8+ and CD4+ T cells in untreated TME were 19.2% and 23.0%, respectively. Upon LAIT, both proportions were increased to 25.5% and 36.2%, respectively. In particular, LAIT increased the proportions of naïve and memory cells from a resting state to an activated state. LAIT consistently induced the expression of co‐stimulatory molecules, type I IFN responsive genes, and a series of antitumor cytokines, Ifng, Tnf, Il1, and Il17 in CD8+ and CD4+ T cells. LAIT also induced immune checkpoints Pdcd1, Ctla4, and Lag3 expression, consistent with T cell activation. Relevant to clinical translation, LAIT also upregulated genes in CD8+ and CD4+ T cells that positively correlated with extended survival of breast cancer patients. Conclusions Overall, our results reveal that LAIT prompts immunological remodelling of T cells by inducing broad proinflammatory responses and inhibiting suppressive signalling to drive antitumour immunity.
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Affiliation(s)
- Ashley R Hoover
- Stephenson School of Biomedical Engineering, University of Oklahoma, Norman, Oklahoma, USA.,Arthritis & Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA
| | - Kaili Liu
- Stephenson School of Biomedical Engineering, University of Oklahoma, Norman, Oklahoma, USA
| | - Christa I DeVette
- Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA
| | - Jason R Krawic
- Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA
| | - Alexandra D Medcalf
- Arthritis & Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA
| | - Connor L West
- Stephenson School of Biomedical Engineering, University of Oklahoma, Norman, Oklahoma, USA
| | - Tomas Hode
- Immunophotonics Inc., St. Louis, Missouri, USA
| | | | - Alana L Welm
- Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah, USA
| | - Xiao-Hong Sun
- Arthritis & Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA
| | - William H Hildebrand
- Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA
| | - Wei R Chen
- Stephenson School of Biomedical Engineering, University of Oklahoma, Norman, Oklahoma, USA
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Paoletti L, Ceccarelli C, Menichelli C, Aristei C, Borghesi S, Tucci E, Bastiani P, Cozzi S. Special stereotactic radiotherapy techniques: procedures and equipment for treatment simulation and dose delivery. Rep Pract Oncol Radiother 2022; 27:1-9. [PMID: 35402024 PMCID: PMC8989452 DOI: 10.5603/rpor.a2021.0129] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2021] [Accepted: 11/14/2021] [Indexed: 12/25/2022] Open
Abstract
Stereotactic radiotherapy (SRT ) is a multi-step procedure with each step requiring extreme accuracy. Physician-dependent accuracy includes appropriate disease staging, multi-disciplinary discussion with shared decision-making, choice of morphological and functional imaging methods to identify and delineate the tumor target and organs at risk, an image-guided patient set-up, active or passive management of intra-fraction movement, clinical and instrumental follow-up. Medical physicist-dependent accuracy includes use of advanced software for treatment planning and more advanced Quality Assurance procedures than required for conventional radiotherapy. Consequently, all the professionals require appropriate training in skills for high-quality SRT. Thanks to the technological advances, SRT has moved from a “frame-based” technique, i.e. the use of stereotactic coordinates which are identified by means of rigid localization frames, to the modern “frame-less” SRT which localizes the target volume directly, or by means of anatomical surrogates or fiducial markers that have previously been placed within or near the target. This review describes all the SRT steps in depth, from target simulation and delineation procedures to treatment delivery and image-guided radiation therapy. Target movement assessment and management are also described.
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Affiliation(s)
- Lisa Paoletti
- Radiotherapy Unit, AUSL Toscana Centro, Florence, Italy
| | | | | | - Cynthia Aristei
- Radiation Oncology Section, University of Perugia and Perugia General Hospital, Italy
| | - Simona Borghesi
- Radiation Oncology Unit of Arezzo-Valdarno, Azienda USL Toscana Sud Est, Italy
| | - Enrico Tucci
- Radiation Oncology Unit of Arezzo-Valdarno, Azienda USL Toscana Sud Est, Italy
| | | | - Salvatore Cozzi
- Radiation Oncology Unit, Azienda Unità Sanitaria Locale - IRCCS di Reggio Emilia, Italy
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Tao ZW, Cheng BQ, Zhou T, Gao YJ. Management of hepatocellular carcinoma patients with portal vein tumor thrombosis: A narrative review. Hepatobiliary Pancreat Dis Int 2022; 21:134-144. [PMID: 34955380 DOI: 10.1016/j.hbpd.2021.12.004] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2021] [Accepted: 11/05/2021] [Indexed: 02/09/2023]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is one of the main reasons for malignancy-related death. Portal vein tumor thrombosis (PVTT) is the most common form of macrovascular invasion related to HCC occurring in 10%-60% of patients. HCC with PVTT is usually characterized by worsening liver function, vulnerability to blood metastasis, higher incidence of complications associated with portal hypertension, and intolerance to treatment when compared with that without PVTT. If only treated with supportive care, the median survival of HCC with PVTT is about 2.7 months. In the past, sorafenib was the only recommended therapy by guidelines with limited effectiveness. This narrative review aimed to describe the current management options for HCC with PVTT. DATA SOURCES We have reviewed literature from PubMed on the treatment of HCC with PVTT and compiled evidence-based facts on effective therapies available for different types of PVTT. RESULTS Sorafenib monotherapy is not much effective, but combining it with other methods can improve survival. Each type of PVTT can benefit from the combination of transarterial chemoembolization and sorafenib than sorafenib monotherapy. The tumor downstaging can be realized possibly after transarterial chemoembolization, but tumor invasion into the main trunk of the portal vein greatly impairs efficacy. Although surgery is a curative approach, it is often not recommended for Vp4 PVTT. Some new methods can broaden the indication, but further explorations are needed. Radiotherapy can decrease the possibility of Vp3 progression to Vp4, but building a forecast model of best radiation dose and response is necessary. Systemic chemotherapy, hepatic arterial infusion chemotherapy, radiofrequency ablation, portal stenting, and traditional Chinese medicine are also beneficial in Vp3-4 PVTT. The accurate diagnosis of PVTT can be made by radiomics, and prognostic classification models can be used to design personalized treatments. The application of new treatment methods such as the atezolizumab plus bevacizumab scheme may increase survival. CONCLUSIONS HCC with PVTT is still a thorny problem, and effective therapeutics need to be explored.
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Affiliation(s)
- Zi-Wen Tao
- Department of Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
| | - Bao-Quan Cheng
- Department of Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
| | - Tao Zhou
- Department of Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
| | - Yan-Jing Gao
- Department of Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, China.
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Kinj R, Muggeo E, Schiappacasse L, Bourhis J, Herrera FG. Stereotactic Body Radiation Therapy in Patients with Oligometastatic Disease: Clinical State of the Art and Perspectives. Cancers (Basel) 2022; 14:1152. [PMID: 35267460 PMCID: PMC8909365 DOI: 10.3390/cancers14051152] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2022] [Revised: 02/16/2022] [Accepted: 02/22/2022] [Indexed: 02/06/2023] Open
Abstract
Stereotactic body radiation therapy (SBRT) is a form of radiation therapy (RT) in which a small number of high doses of radiation are delivered to a target volume using highly sophisticated equipment. Stereotactic body radiation therapy is crucial in two cancer stages: early primary cancer and oligometastatic disease, with the goal of inducing complete cancer remission in both. This treatment method is commonly used to treat a variety of disease types. Over the years, a growing body of clinical evidence on the use of SBRT for the treatment of primary and metastatic tumors has accumulated, with efficacy and safety demonstrated in randomized clinical trials. This article will review the technical and clinical aspects of SBRT according to disease type and clinical indication.
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Affiliation(s)
- Rémy Kinj
- Service of Radiation Oncology, Department of Oncology, Lausanne University Hospital, 1010 Lausanne, Switzerland; (E.M.); (L.S.); (J.B.)
| | - Emilien Muggeo
- Service of Radiation Oncology, Department of Oncology, Lausanne University Hospital, 1010 Lausanne, Switzerland; (E.M.); (L.S.); (J.B.)
| | - Luis Schiappacasse
- Service of Radiation Oncology, Department of Oncology, Lausanne University Hospital, 1010 Lausanne, Switzerland; (E.M.); (L.S.); (J.B.)
| | - Jean Bourhis
- Service of Radiation Oncology, Department of Oncology, Lausanne University Hospital, 1010 Lausanne, Switzerland; (E.M.); (L.S.); (J.B.)
| | - Fernanda G. Herrera
- Service of Radiation Oncology, Department of Oncology, Lausanne University Hospital, 1010 Lausanne, Switzerland; (E.M.); (L.S.); (J.B.)
- Service of Immuno-Oncology, Department of Oncology, Lausanne University Hospital and University of Lausanne, 1010 Lausanne, Switzerland
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