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Bashir B, Sethi P, Panda S, Manikyam HK, Vishwas S, Singh SK, Singh K, Jain D, Chaitanya MVNL, Coutinho HDM. Unravelling the epigenetic based mechanism in discovery of anticancer phytomedicine: Evidence based studies. Cell Signal 2025; 131:111743. [PMID: 40107479 DOI: 10.1016/j.cellsig.2025.111743] [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: 01/15/2025] [Revised: 03/10/2025] [Accepted: 03/11/2025] [Indexed: 03/22/2025]
Abstract
Epigenetic mechanisms play a crucial role in the normal development and maintenance of tissue-specific gene expression patterns in mammals. Disruption of these processes can result in changes to gene function and the transformation of cells into a malignant state. Cancer is characterized by widespread alterations in the epigenetic landscape, revealing that it involves not only genetic mutations but also epigenetic abnormalities. Recent progress in the field of cancer epigenetics has demonstrated significant reprogramming of various components of the epigenetic machinery in cancer, such as DNA methylation, modifications to histones, positioning of nucleosomes, and the expression of non-coding RNAs, particularly microRNAs. The ability to reverse epigenetic abnormalities has given rise to the hopeful field of epigenetic therapy, which has shown advancement with the recent approval by the FDA of three drugs targeting epigenetic mechanisms for the treatment of cancer. In the present manuscript, a comprehensive review has been presented about the role of understanding the epigenetic link between cancer and mechanisms by which phytomedicine offers treatment avenues. Further, this review deciphers the significance of natural products in the identification of epigenetic therapeutics, the diversity of their molecular targets, the use of nanotechnology, and the creation of new strategies for overcoming the inherent clinical challenges associated with developing these drug leads.
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Affiliation(s)
- Bushra Bashir
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab 144402, India
| | - Pranshul Sethi
- Department of Pharmacology, College of Pharmacy, Shri Venkateshwara University, Gajraula, Uttar Pradesh, India
| | - Satyajit Panda
- Department of Pharmaceutics, Institute of Pharmacy and Technology, Salipur, Cuttack, Odisha 754202, India
| | - Hemanth Kumar Manikyam
- Department of Chemistry, Faculty of science, North East Frontier Technical University, Arunachal Pradesh 791001, India
| | - Sukriti Vishwas
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab 144402, India
| | - Sachin Kumar Singh
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab 144402, India
| | - Kuldeep Singh
- Department of Pharmacology, Institute of Pharmaceutical Research, GLA University, Mathura, Uttar Pradesh, India.
| | - Divya Jain
- Department of Microbiology, School of Applied and Life sciences, Uttaranchal University, Dehradun, Uttarakhand 248007, India.
| | - M V N L Chaitanya
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab 144402, India.
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Niazi T, Nabid A, Malagon T, Tisseverasinghe S, Bettahar R, Dahmane R, Martin AG, Jolicoeur M, Yassa M, Barkati M, Igidbashian L, Bahoric B, Archambault R, Villeneuve H, Mohiuddin M. Hypofractionated Dose Escalation Radiotherapy for High-Risk Prostate Cancer: the survival analysis of the Prostate Cancer Study-5 (PCS-5), a GROUQ-led phase III trial. Eur Urol 2025; 87:314-323. [PMID: 39271420 DOI: 10.1016/j.eururo.2024.08.032] [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: 03/17/2024] [Revised: 06/24/2024] [Accepted: 08/27/2024] [Indexed: 09/15/2024]
Abstract
BACKGROUND AND OBJECTIVE Prostate Cancer Study 5 (PCS5) compared conventional fractionated radiotherapy (CFRT) with hypofractionated radiotherapy (HFRT) in high-risk prostate cancer (PCa) patients, hypothesizing similar toxicity and survival outcomes. This report presents the efficacy analysis. METHODS PCS5 is a Canadian multicenter, open-label, phase 3 randomized control trial. Men with histologically proven, clinically localized PCa with one or more high-risk features (T3/T4, Gleason score ≥8, and prostate-specific antigen >20) were eligible. Patients were randomized 1:1 to CFRT (76 Gy/38 fractions [Fx] to the prostate and 46 Gy/23 Fx to the pelvic lymph nodes [PLNs]) or HFRT (68 Gy/25 Fx to the prostate and 45 Gy/25 Fx to the PLNs) and 28 mo of androgen suppression. The primary endpoint was toxicity; secondary endpoints included survival outcomes. KEY FINDINGS AND LIMITATIONS Of 329 patients, 164 were randomized to HFRT and 165 to CFRT, with 159 in the HFRT arm and 160 in the CFRT arm included in survival analyses. At the 5-yr median follow-up, there were no significant differences in overall survival (OS; 90.3% vs 89.7%; risk ratio [RR]: 1.01; 95% confidence interval [CI]: 0.93-1.09), PCa-specific survival (PCSS; 97.4% vs 97.5%; RR: 1.00; 95% CI: 0.93-1.07), biochemical recurrence-free survival (BCRFS; 85.2% vs 85.2%; RR: 1.00; 95% CI: 0.91-1.10), or distant metastasis-free survival (DMFS; 87.1% vs 87.1%; RR: 1.00; 95% CI: 0.92-1.09). Hazard ratios were 0.92 (95% CI: 0.56-1.53) for OS, 1.31 (95% CI: 0.46-3.78) for PCSS, 0.85 (95% CI: 0.56-1.30) for BCRFS, and 0.90 (95% CI: 0.56-1.43) for DMFS. Sample size was a limiting factor. CONCLUSIONS AND CLINICAL IMPLICATIONS There were no differences in survival outcomes between HFRT (68 Gy/25 Fx) and CFRT (76 Gy/38 Fx). HFRT, including PLN radiotherapy and long-term androgen deprivation therapy, should be considered a new standard of care for high-risk PCa patients undergoing external beam radiotherapy.
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Affiliation(s)
- Tamim Niazi
- Jewish General Hospital, McGill University, Montreal, Quebec, Canada.
| | - Abdenour Nabid
- Centre Hospitalier Universitaire de Sherbrooke (CHUS), Sherbrooke, Quebec, Canada
| | - Talia Malagon
- Department of Oncology, McGill University, Montréal, Quebec, Canada; St Mary's Research Centre, Montréal West Island CIUSSS, Montréal, Quebec, Canada
| | | | - Redouane Bettahar
- Centre Hospitalier Régional de Rimouski-Centre de Cancer, Rimouski, Quebec, Canada
| | - Rafika Dahmane
- Pavillon Ste-Marie Centre Hospitalier Régional de Trois-Rivières (CHRTR), Trois-Rivières, Quebec, Canada
| | - Andre-Guy Martin
- Centre Hospitalier Universitaire de Québec (CHUQ)-L'Hôtel-Dieu de Québec, Quebec City, Quebec, Canada
| | | | - Michael Yassa
- Hôpital Maisonneuve-Rosemont, Montreal, Quebec, Canada
| | - Maroie Barkati
- Centre Hospitalier de l'Université de Montréal (CHUM) (MB), Montreal, Quebec, Canada
| | | | - Boris Bahoric
- Jewish General Hospital, McGill University, Montreal, Quebec, Canada
| | | | | | - Md Mohiuddin
- Saint John Regional Hospital (MM), Saint John, New Brunswick, Canada
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Wisdom AJ, Yeap BY, Michalski JM, Horick NK, Zietman AL, Christodouleas JP, Kamran SC, Parikh RR, Vapiwala N, Mihalcik S, Miyamoto DT, Zeng J, Gay HA, Pisansky TM, Mishra MV, Spratt DE, Mendenhall NP, Soffen EM, Bekelman JE, Efstathiou JA. Setting the Stage: Feasibility and Baseline Characteristics in the PARTIQoL Trial Comparing Proton Therapy Versus Intensity Modulated Radiation Therapy for Localized Prostate Cancer. Int J Radiat Oncol Biol Phys 2025; 121:741-751. [PMID: 39357788 DOI: 10.1016/j.ijrobp.2024.09.043] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2024] [Revised: 09/23/2024] [Accepted: 09/23/2024] [Indexed: 10/04/2024]
Abstract
PURPOSE Men with localized prostate cancer may receive either photon-based intensity modulated radiation therapy (IMRT) or proton beam therapy (PBT). The PARTIQoL trial (NCT01617161) demonstrates the feasibility of performing a large, multicenter phase 3 randomized trial comparing IMRT with PBT for localized prostate cancer. Here, we report baseline features of patients enrolled on this trial and present strategies to improve feasibility of other similar trials. METHODS AND MATERIALS Patients with low- or intermediate-risk prostate cancer were randomly assigned to either PBT or IMRT with stratification by institution, age, use of rectal spacer, and fractionation schedule (conventional fractionation: 79.2 Gy in 44 fractions vs moderate hypofractionation: 70.0 Gy in 28 fractions). The primary endpoint is a change from baseline bowel health using the Expanded Prostate Index Composite score 24 months after radiation therapy. Secondary objectives include treatment-related differences in urinary and erectile functions, adverse events, and efficacy endpoints. RESULTS Between July 2012 and November 2021, 450 patients were successfully accrued. Patients were randomly assigned to either PBT (N = 226) or to IMRT (N = 224); 13 were ineligible or withdrew before treatment. The median age of 437 analyzed patients was 68 years (range, 46-89 years). A total of 41% of patients had low-risk and 59% had intermediate-risk disease. In total, 49% of patients were treated with conventional fractionation and 51% with moderately hypofractionation. 48% of patients used a rectal spacer. For patients receiving PBT, pencil beam scanning was used in 48%. PBT and IMRT arms were balanced for baseline variables. CONCLUSIONS Despite significant challenges, the PARTIQoL trial demonstrated that, with targeted recruitment approaches, multicenter collaboration, payer engagement, and protocol updates to incorporate contemporary techniques, it is feasible to perform a large phase 3 randomized clinical trial to assess whether PBT improves outcomes. We will separately report primary results and continue to monitor participants for longer follow-up and secondary endpoints.
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Affiliation(s)
- Amy J Wisdom
- Department Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
| | - Beow Y Yeap
- Department Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
| | - Jeff M Michalski
- Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri
| | - Nora K Horick
- Department Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
| | - Anthony L Zietman
- Department Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
| | - John P Christodouleas
- Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Sophia C Kamran
- Department Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
| | - Rahul R Parikh
- Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey
| | - Neha Vapiwala
- Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Stephen Mihalcik
- Department of Radiation Oncology, Northwestern Medicine, Feinberg School of Medicine, Chicago, Illinois
| | - David T Miyamoto
- Department Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
| | - Jing Zeng
- Department of Radiation Oncology, University of Washington - Fred Hutchinson Cancer Center, Seattle, Washington
| | - Hiram A Gay
- Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri
| | | | - Mark V Mishra
- Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, Maryland
| | - Daniel E Spratt
- University Hospitals Seidman Cancer Center, Case Western Reserve University, Cleveland, Ohio
| | - Nancy P Mendenhall
- Department of Radiation Oncology, University of Florida College of Medicine, Gainesville, Florida
| | - Edward M Soffen
- Princeton Radiation Oncology, Astera Cancer Care, Jamesburg, New Jersey
| | - Justin E Bekelman
- Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Jason A Efstathiou
- Department Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
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Xiong Y, Li J, Jiang X, Zhen W, Ma X, Lin W. Nitric Oxide-Releasing Nanoscale Metal-Organic Layer Overcomes Hypoxia and Reactive Oxygen Species Diffusion Barriers to Enhance Cancer Radiotherapy. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2025; 12:e2413518. [PMID: 39742392 PMCID: PMC11848595 DOI: 10.1002/advs.202413518] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/23/2024] [Revised: 12/17/2024] [Indexed: 01/03/2025]
Abstract
Hafnium (Hf)-based nanoscale metal-organic layers (MOLs) enhance radiotherapeutic effects of tissue-penetrating X-rays via a unique radiotherapy-radiodynamic therapy (RT-RDT) process through efficient generation of hydroxy radical (RT) and singlet oxygen (RDT). However, their radiotherapeutic efficacy is limited by hypoxia in deep-seated tumors and short half-lives of reactive oxygen species (ROS). Herein the conjugation of a nitric oxide (NO) donor, S-nitroso-N-acetyl-DL-penicillamine (SNAP), to the Hf12 secondary building units (SBUs) of Hf-5,5'-di-p-benzoatoporphyrin MOL is reported to afford SNAP/MOL for enhanced cancer radiotherapy. Under X-ray irradiation, SNAP/MOL efficiently generates superoxide anion (O2 -.) and releases nitric oxide (NO) in a spatio-temporally synchronized fashion. The released NO rapidly reacts with O2 -. to form long-lived and highly cytotoxic peroxynitrite which diffuses freely to the cell nucleus and efficiently causes DNA double-strand breaks. Meanwhile, the sustained release of NO from SNAP/MOL in the tumor microenvironment relieves tumor hypoxia to reduce radioresistance of tumor cells. Consequently, SNAP/MOL plus low-dose X-ray irradiation efficiently inhibits tumor growth and reduces metastasis in colorectal and triple-negative breast cancer models.
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Affiliation(s)
- Yuxuan Xiong
- Department of ChemistryThe University of ChicagoChicagoIL60637USA
| | - Jinhong Li
- Department of ChemistryThe University of ChicagoChicagoIL60637USA
| | - Xiaomin Jiang
- Department of ChemistryThe University of ChicagoChicagoIL60637USA
| | - Wenyao Zhen
- Department of ChemistryThe University of ChicagoChicagoIL60637USA
| | - Xin Ma
- Department of ChemistryThe University of ChicagoChicagoIL60637USA
| | - Wenbin Lin
- Department of ChemistryThe University of ChicagoChicagoIL60637USA
- Department of Radiation and Cellular Oncology and the Ludwig Center for Metastasis ResearchThe University of ChicagoChicagoIL60637USA
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Yaremenko AV, Khan MM, Zhen X, Tang Y, Tao W. Clinical advances of mRNA vaccines for cancer immunotherapy. MED 2025; 6:100562. [PMID: 39798545 DOI: 10.1016/j.medj.2024.11.015] [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: 09/13/2024] [Revised: 11/06/2024] [Accepted: 11/25/2024] [Indexed: 01/15/2025]
Abstract
The development of mRNA vaccines represents a significant advancement in cancer treatment, with more than 120 clinical trials to date demonstrating their potential across various malignancies, including lung, breast, prostate, melanoma, and more challenging cancers such as pancreatic and brain tumors. These vaccines work by encoding tumor-specific antigens and immune-stimulating molecules, effectively activating the immune system to target and eliminate cancer cells. Despite these promising advancements, significant challenges remain, particularly in achieving efficient delivery and precise regulation of the immune response. This review provides a comprehensive overview of recent clinical progress in mRNA cancer vaccines, discusses the innovative strategies being employed to overcome existing hurdles, and explores future directions, including the integration of CRISPR-Cas9 technology and advancements in mRNA design. Our aim is to provide insights into the ongoing research and clinical trials, highlighting the transformative potential of mRNA vaccines in advancing oncology and improving patient outcomes.
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Affiliation(s)
- Alexey V Yaremenko
- Center for Nanomedicine, Department of Anesthesiology, Perioperative, and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA
| | - Muhammad Muzamil Khan
- Center for Nanomedicine, Department of Anesthesiology, Perioperative, and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA
| | - Xueyan Zhen
- Center for Nanomedicine, Department of Anesthesiology, Perioperative, and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA
| | - Yan Tang
- Pulmonary and Critical Care Medicine, Development of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
| | - Wei Tao
- Center for Nanomedicine, Department of Anesthesiology, Perioperative, and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
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Mattes MD. Overview of Radiation Therapy in the Management of Localized and Metastatic Prostate Cancer. Curr Urol Rep 2024; 25:181-192. [PMID: 38861238 DOI: 10.1007/s11934-024-01217-5] [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] [Accepted: 06/05/2024] [Indexed: 06/12/2024]
Abstract
PURPOSE OF REVIEW The goal is to describe the evolution of radiation therapy (RT) utilization in the management of localized and metastatic prostate cancer. RECENT FINDINGS Long term data for a variety of hypofractionated definitive RT dose-fractionation schemes has matured, allowing patients and providers many standard-of-care options to choose from. Post-prostatectomy, adjuvant RT has largely been replaced by an early salvage approach. Multiparametric MRI and PSMA PET have enabled increasingly targeted RT delivery to the prostate and oligometastatic tumors. Areas of active investigation include determining the value of proton beam therapy and perirectal spacers, and optimally incorporate genomic tumor profiling and next generation hormonal therapies with RT in the curative setting. The use of radiation therapy to treat prostate cancer is rapidly evolving. In the coming years, there will be continued improvements in a variety of areas to enhance the value of RT in multidisciplinary prostate cancer management.
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Affiliation(s)
- Malcolm D Mattes
- Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, 195 Little Albany Street, New Brunswick, NJ, 08901, USA.
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Fu Q, Gu Z, Shen S, Bai Y, Wang X, Xu M, Sun P, Chen J, Li D, Liu Z. Radiotherapy activates picolinium prodrugs in tumours. Nat Chem 2024; 16:1348-1356. [PMID: 38561425 DOI: 10.1038/s41557-024-01501-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2023] [Accepted: 03/05/2024] [Indexed: 04/04/2024]
Abstract
Radiotherapy-induced prodrug activation provides an ideal solution to reduce the systemic toxicity of chemotherapy in cancer therapy, but the scope of the radiation-activated protecting groups is limited. Here we present that the well-established photoinduced electron transfer chemistry may pave the way for developing versatile radiation-removable protecting groups. Using a functional reporter assay, N-alkyl-4-picolinium (NAP) was identified as a caging group that efficiently responds to radiation by releasing a client molecule. When evaluated in a competition experiment, the NAP moiety is more efficient than other radiation-removable protecting groups discovered so far. Leveraging this property, we developed a NAP-derived carbamate linker that releases fluorophores and toxins on radiation, which we incorporated into antibody-drug conjugates (ADCs). These designed ADCs were active in living cells and tumour-bearing mice, highlighting the potential to use such a radiation-removable protecting group for the development of next-generation ADCs with improved stability and therapeutic effects.
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Affiliation(s)
- Qunfeng Fu
- Changping Laboratory, Beijing, China
- Beijing National Laboratory for Molecular Sciences, Radiochemistry and Radiation Chemistry Key Laboratory of Fundamental Science, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, College of Chemistry and Molecular Engineering, Peking University, Beijing, China
| | - Zhi Gu
- Changping Laboratory, Beijing, China
- Beijing National Laboratory for Molecular Sciences, Radiochemistry and Radiation Chemistry Key Laboratory of Fundamental Science, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, College of Chemistry and Molecular Engineering, Peking University, Beijing, China
| | - Siyong Shen
- Beijing National Laboratory for Molecular Sciences, Radiochemistry and Radiation Chemistry Key Laboratory of Fundamental Science, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, College of Chemistry and Molecular Engineering, Peking University, Beijing, China
| | - Yifei Bai
- Beijing National Laboratory for Molecular Sciences, Radiochemistry and Radiation Chemistry Key Laboratory of Fundamental Science, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, College of Chemistry and Molecular Engineering, Peking University, Beijing, China
| | - Xianglin Wang
- Beijing National Laboratory for Molecular Sciences, Radiochemistry and Radiation Chemistry Key Laboratory of Fundamental Science, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, College of Chemistry and Molecular Engineering, Peking University, Beijing, China
| | - Mengxin Xu
- Beijing National Laboratory for Molecular Sciences, Radiochemistry and Radiation Chemistry Key Laboratory of Fundamental Science, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, College of Chemistry and Molecular Engineering, Peking University, Beijing, China
| | - Pengwei Sun
- Beijing National Laboratory for Molecular Sciences, Radiochemistry and Radiation Chemistry Key Laboratory of Fundamental Science, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, College of Chemistry and Molecular Engineering, Peking University, Beijing, China
| | - Junyi Chen
- Beijing National Laboratory for Molecular Sciences, Radiochemistry and Radiation Chemistry Key Laboratory of Fundamental Science, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, College of Chemistry and Molecular Engineering, Peking University, Beijing, China
| | - Dongxuan Li
- Beijing National Laboratory for Molecular Sciences, Radiochemistry and Radiation Chemistry Key Laboratory of Fundamental Science, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, College of Chemistry and Molecular Engineering, Peking University, Beijing, China
| | - Zhibo Liu
- Changping Laboratory, Beijing, China.
- Beijing National Laboratory for Molecular Sciences, Radiochemistry and Radiation Chemistry Key Laboratory of Fundamental Science, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, College of Chemistry and Molecular Engineering, Peking University, Beijing, China.
- Peking University-Tsinghua University Center for Life Sciences, Peking University, Beijing, China.
- Key Laboratory of Carcinogenesis and Translational Research of Ministry of Education, NMPA Key Laboratory for Research and Evaluation of Radiopharmaceuticals, Department of Nuclear Medicine, Peking University Cancer Hospital and Institute, Beijing, China.
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Sritharan K, Daamen L, Pathmanathan A, Schytte T, Pos F, Choudhury A, van der Voort van Zyp JR, Kerkmeijer LG, Hall W, Hall E, Verkooijen HM, Herbert T, Hafeez S, Mitchell A, Tree AC. MRI-guided radiotherapy in twenty fractions for localised prostate cancer; results from the MOMENTUM study. Clin Transl Radiat Oncol 2024; 46:100742. [PMID: 38440792 PMCID: PMC10909700 DOI: 10.1016/j.ctro.2024.100742] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2023] [Revised: 01/30/2024] [Accepted: 02/03/2024] [Indexed: 03/06/2024] Open
Abstract
Background and purpose MRI-guided radiotherapy (MRIgRT) offers multiple potential advantages over CT-guidance. This study examines the potential clinical benefits of MRIgRT for men with localised prostate cancer, in the setting of moderately hypofractionated radiotherapy. We evaluate two-year toxicity outcomes, early biochemical response and patient-reported outcomes (PRO), using data obtained from a multicentre international registry study, for the first group of patients with prostate cancer who underwent treatment on a 1.5 T MR-Linac. Materials and methods Patients who were enrolled within the MOMENTUM study and received radical treatment with 60 Gy in 20 fractions were identified. PSA levels and CTCAE version 5.0 toxicity data were measured at follow-up visits. Those patients who consented to PRO data collection also completed EQ-5D-5L, EORTC QLQ-C30 and EORTC QLQ-PR25 questionnaires. Results Between November 2018 and June 2022, 146 patients who had MRIgRT for localised prostate cancer on the 1.5 T MR-Linac were eligible for this study. Grade 2 and worse gastro-intestinal (GI) toxicity was reported in 3 % of patients at three months whilst grade 2 and worse genitourinary (GU) toxicity was 7 % at three months. There was a significant decrease in the median PSA at 12 months. The results from both the EQ-5D-5L data and EORTC global health status scale indicate a decline in the quality of life (QoL) during the first six months. The mean change in score for the EORTC scale showed a decrease of 11.4 points, which is considered clinically important. QoL improved back to baseline by 24 months. Worsening of hormonal symptoms in the first six months was reported with a return to baseline by 24 months and sexual activity in all men worsened in the first three months and returned to baseline at 12 months. Conclusion This study establishes the feasibility of online-MRIgRT for localised prostate on a 1.5 T MR-Linac with low rates of toxicity, similar to that published in the literature. However, the clinical benefits of MRIgRT over conventional radiotherapy in the setting of moderate hypofractionation is not evident. Further research will focus on the delivery of ultrahypofractionated regimens, where the potential advantages of MRIgRT for prostate cancer may become more discernible.
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Affiliation(s)
- Kobika Sritharan
- The Royal Marsden NHS Foundation Trust, UK
- The Institute of Cancer Research, UK
| | - Lois Daamen
- Division of Imaging and Oncology, University Medical Center Utrecht, Utrecht, the Netherlands
| | | | | | - Floris Pos
- The Netherlands Cancer Institute, The Netherlands
| | - Ananya Choudhury
- Division of Cancer Sciences, University of Manchester and The Christie NHS Foundation Trust, UK
| | | | | | | | - Emma Hall
- The Institute of Cancer Research, UK
| | - Helena M. Verkooijen
- Division of Imaging and Oncology, University Medical Center Utrecht, Utrecht, the Netherlands
| | | | | | - Adam Mitchell
- The Royal Marsden NHS Foundation Trust, UK
- The Institute of Cancer Research, UK
| | - Alison C. Tree
- The Royal Marsden NHS Foundation Trust, UK
- The Institute of Cancer Research, UK
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Niazi T, Nabid A, Malagon T, Bettahar R, Vincent L, Martin AG, Jolicoeur M, Yassa M, Barkati M, Igidbashian L, Bahoric B, Archambault R, Villeneuve H, Tsui JMG, Mohiuddin M. Hypofractionated, Dose Escalation Radiation Therapy for High-Risk Prostate Cancer: The Safety Analysis of the Prostate Cancer Study-5, a Groupe de Radio-Oncologie Génito-Urinaire de Quebec Led Phase 3 Trial. Int J Radiat Oncol Biol Phys 2024; 118:52-62. [PMID: 37224928 DOI: 10.1016/j.ijrobp.2023.05.014] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2022] [Revised: 04/27/2023] [Accepted: 05/08/2023] [Indexed: 05/26/2023]
Abstract
PURPOSE The low α\β ratio of 1.2 to 2 for prostate cancer (PCa) suggests high radiation-fraction sensitivity and predicts a therapeutic advantage of hypofractionated (HF) radiation therapy (RT). To date, no phase 3 randomized clinical trial has compared moderately HF RT with standard fractionation (SF) exclusively in high-risk PCa patients. We are reporting the safety of moderate HF RT in high-risk PCa in an initially noninferiority-designed phase 3 clinical trial. METHODS AND MATERIALS From February 2012 to March 2015, 329 high-risk PCa patients were randomized to receive either SF or HF RT. All patients received neoadjuvant, concurrent, and long-term adjuvant androgen deprivation therapy. Standard fractionation RT consisted of 76 Gy in 2 Gy per fraction to the prostate, where 46 Gy was delivered to the pelvic lymph nodes. Hypofractionated RT included concomitant dose escalation of 68 Gy in 2.72 Gy per fraction to the prostate and 45 Gy in 1.8 Gy per fraction to the pelvic lymph nodes. The coprimary endpoints were acute and delayed toxicity at 6 and 24 months, respectively. The trial was originally designed as a noninferiority with a 5% absolute margin. Given the lower-than-expected toxicities in both arms, the noninferiority analysis was completely dropped. RESULTS Of the 329 patients, 164 were randomized to the HF and 165 to the SF arms. In total, there were more grade 1 or worse acute gastrointestinal (GI) events in the HF arm, 102 versus 83 events in the HF and SF arm, respectively (P = .016). This did not remain significant at 8 weeks of follow-up. There were no differences in grade 1 or worse acute GU events in the 2 arms, 105 versus 99 events in the HF and SF arm, respectively (P = .3). At 24 months, 12 patients in the SF arm and 15 patients in the HF arm had grade 2 or worse delayed GI-related adverse events (hazard ratio, 1.32; 95% CI, 0.62-2.83; P = .482). There were 11 patients in the SF arm and 3 patients in the HF arm with grade 2 or higher delayed genitourinary (GU) toxicities (hazard ratio, 0.26; 95% CI, 0.07-0.94; P = .037). There were 3 grade 3 GI and one grade 3 GU delayed toxicities in the HF arm and 3 grade 3 GU and no grade 3 GI toxicities in the SF arm. No grade 4-toxicities were reported. CONCLUSIONS This is the first study of moderate HF dose-escalated RT in exclusively high-risk patients with prostate cancer treated with long-term androgen deprivation therapy and pelvic RT. Although our data were not analyzed as a noninferiority, our results demonstrate that moderately HF RT is well-tolerated, similar to SF RT at 2 years, and could be considered an alternative to SF RT.
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Affiliation(s)
- Tamim Niazi
- Department of Oncology, Division of Radiation Onclogy, Hôpital Maisonneuve-Rosemont, Montreal, Quebec, Canada.
| | - Abdenour Nabid
- Department of Oncology, Division of Radiation Onclogy, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Quebec, Canada
| | - Talia Malagon
- Department of Oncology, McGill University, Montreal, Quebec, Canada
| | - Redouane Bettahar
- Division of Radiation Onclogy, Centre Hospitalier Régional de Rimouski-Centre de Cancer, Rimouski, Quebec, Canada
| | - Linda Vincent
- Division of Radiation Onclogy, Pavillon Ste-Marie Centre Hospitalier Régional de Trois-Rivières, Trois-Rivières, Quebec, Canada
| | - Andre-Guy Martin
- Department of Oncology, Division of Radiation Onclogy, Centre Hospitalier Universitaire de Québec-L'Hôtel-Dieu de Québec, Quebec City, Quebec, Canada
| | - Marjory Jolicoeur
- Department of Oncology, Division of Radiation Onclogy, Hôpital Charles LeMoyne, Greenfield Park, Quebec, Canada
| | - Michael Yassa
- Department of Oncology, Division of Radiation Onclogy, Hôpital Maisonneuve-Rosemont, Montreal, Quebec, Canada
| | - Maroie Barkati
- Department of Oncology, Division of Radiation Onclogy, Centre Hospitalier de l'Université de Montréal, Montreal, Quebec, Canada
| | - Levon Igidbashian
- Division of Radiation Onclogy, Hôpital Cité-de-la-Santé, Laval, Quebec, Canada
| | - Boris Bahoric
- Department of Oncology, Division of Radiation Onclogy, Jewish General Hospital, McGill University, Quebec, Canada
| | - Robert Archambault
- Department of Oncology, Division of Radiation Onclogy, Hôpital Gatineau, Gatineau, Quebec, Canada
| | - Hugo Villeneuve
- Department of Oncology, Division of Radiation Onclogy, Hôpital de Chicoutimi, Chicoutimi, Quebec, Canada
| | - James Man Git Tsui
- Department of Oncology, Division of Radiation Onclogy, McGill University Health Centre, Montreal, Quebec, Canada
| | - Mohammed Mohiuddin
- Department of Oncology, Division of Radiation Onclogy, Saint John Regional Hospital (MM), Saint John, New Brunswick, Canada
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Debard C, Margue G, Klein C, Rompré-Brodeur A, Marcq G, Bensadoun H, Robert G, Anidjar M, Bladou F. [Oncological and functional results of focal treatment of localized prostate cancer with HIFU]. Prog Urol 2023; 33:966-973. [PMID: 37770359 DOI: 10.1016/j.purol.2023.09.012] [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: 05/19/2023] [Revised: 09/04/2023] [Accepted: 09/08/2023] [Indexed: 09/30/2023]
Abstract
INTRODUCTION In recent years, improved diagnosis of prostate cancer has allowed the development of focal therapy, in order to reduce the morbidity of treatments. Our study assesses the medium-term oncological and functional results of FocalOne® HIFU treatment in localized prostate cancer. METHODS This is a retrospective, multicentre study including patients with low- or intermediate-risk localized prostate cancer treated with Focal one HIFU between November 2014 and December 2019. The primary endpoint was the retreatment rate and subgroup analyses were performed to identify predictive factors of retreatment. RESULTS One hundred and thirty-seven patients were included with a median follow-up of 25.5 months. Seventy percent of patients had clinical stage T2, 64% had an ISUP score of 2 or 3 on initial biopsies and 38% were treated with hemi-ablation. Follow-up biopsies were performed in 76.6% of patients during follow-up with 21.8% having clinically significant cancers. The retreatment rate at 24 months was 37.2%, with positive biopsies being the primary criterion for retreatment. Patients with a PSA>8ng/mL had a significantly higher retreatment rate. Finally, morbidity remained acceptable with 5.8% of patients requiring reoperation for complications and 21% for de novo erectile dysfunction. CONCLUSION Our results are in agreement with those of the literature, seeming to indicate a lower morbidity of the focal treatment by HIFU compared to the radical treatments while offering an acceptable oncological control. Prospective randomized trials are ongoing. LEVEL OF EVIDENCE: 4
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Affiliation(s)
- C Debard
- Service d'urologie, CHU de Pellegrin, Bordeaux, France.
| | - G Margue
- Service d'urologie, CHU de Pellegrin, Bordeaux, France
| | - C Klein
- Service d'urologie, CHU de Pellegrin, Bordeaux, France
| | - A Rompré-Brodeur
- Department of Surgery (Division of Urology), Mc Gill University Health Center, Montreal, Canada
| | - G Marcq
- Service d'urologie, hôpital Claude-Huriez, CHU de Lille, Lille, France
| | - H Bensadoun
- Service d'urologie, CHU de Pellegrin, Bordeaux, France
| | - G Robert
- Service d'urologie, CHU de Pellegrin, Bordeaux, France
| | - M Anidjar
- Department of Surgery (Division of Urology), Mc Gill University Health Center, Montreal, Canada
| | - F Bladou
- Service d'urologie, CHU de Pellegrin, Bordeaux, France
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11
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Qureshy SA, Diven MA, Ma X, Marciscano AE, Hu JC, McClure TD, Barbieri C, Nagar H. Differential Use of Radiotherapy Fractionation Regimens in Prostate Cancer. JAMA Netw Open 2023; 6:e2337165. [PMID: 37815829 PMCID: PMC10565603 DOI: 10.1001/jamanetworkopen.2023.37165] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2023] [Accepted: 08/29/2023] [Indexed: 10/11/2023] Open
Abstract
Importance Technical advances in treatment of prostate cancer and a better understanding of prostate cancer biology have allowed for hypofractionated treatment courses using a higher dose per fraction. Use of ultrahypofractionated stereotactic body radiotherapy (SBRT) has also been characterized. Objective To characterize US national trends of different RT fractionation schemes across risk groups of prostate cancer. Design, Setting, and Participants This retrospective cohort study used data collected by the National Cancer Database (NCDB) to characterize the fractionation regimens used for 302 035 patients diagnosed as having prostate cancer from January 1, 2004, to December 31, 2020, who underwent definitive RT. The analysis was performed between February 1 and April 30, 2023. Exposure Stereotactic body RT or ultrahypofractionation, defined as 5 or fewer fractions of external beam RT (EBRT), moderate hypofractionation, defined as 20 to 28 fractions of EBRT, or conventional fractionation, defined as all remaining EBRT fractionation schemes. Main Outcomes and Measures Temporal trends and clinical and sociodemographic factors associated with SBRT, moderate hypofractionation, and conventional fractionation use. Results A total of 302 035 men receiving EBRT for localized prostate cancer between 2004 and 2020 were identified (40.1% aged 60-69 years). Black patients comprised 17.6% of this cohort; White patients, 77.9%; and other races and ethnicities, 4.5%. Patients with low-risk disease comprised 17.5% of the cohort; favorable intermediate-risk disease, 23.5%; unfavorable intermediate-risk disease, 23.9%; and high-risk disease, 35.1%. Treatment consisted of conventional fractionation for 81.2%, moderate hypofractionation for 12.9%, and SBRT for 6.0%. The rate of increase over time in patients receiving SBRT compared with conventional fractionation was higher (adjusted odds ratio [AOR] for 2005 vs 2004, 3.18 [95% CI, 2.04-4.94; P < .001]; AOR for 2020 vs 2004, 264.69 [95% CI, 179.33-390.68; P < .001]) than the rate of increase in patients receiving moderate hypofractionation compared with conventional fractionation (AOR for 2005 vs 2004, 1.05 [95% CI, 0.98-1.12; P = .19]; AOR for 2020 vs 2004, 4.41 [95% CI, 4.15-4.69; P < .001]). Compared with White patients, Black patients were less likely to receive SBRT compared with conventional fractionation or moderate hypofractionation (AOR for conventional fractionation, 0.84 [95% CI, 0.80-0.89; P < .001]; AOR for moderate hypofractionation, 0.77 [95% CI, 0.72-0.81; P < .001]). Compared with 2019, patients treated with all fractionation regimens declined in 2020 by 24.4%. Conclusions and Relevance In this hospital-based cohort study of patients with prostate cancer treated with definitive EBRT, use of moderate hypofractionation and SBRT regimens for definitive prostate cancer treatment has increased from 2004 to 2020. Despite this increasing trend, findings suggest potential health care disparities for Black patients receiving EBRT for localized prostate cancer. The number of patients treated with EBRT in the year 2020 decreased, coinciding with official onset of the COVID-19 pandemic in March 2020.
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Affiliation(s)
- Sarah A. Qureshy
- currently a medical student at Weill Cornell Medicine, New York, New York
| | - Marshall A. Diven
- New York Presbyterian-Brooklyn Methodist Hospital, Brooklyn, New York
| | - Xiaoyue Ma
- Department of Population Health Sciences, Division of Biostatistics, Weill Cornell Medicine, New York, New York
| | - Ariel E. Marciscano
- Department of Radiation Oncology, Weill Cornell Medicine/NewYork-Presbyterian, New York, New York
| | - Jim C. Hu
- New York Presbyterian/Weill Cornell Medical Center, New York, New York
| | - Tim D. McClure
- Department of Urology, Weill Cornell Medicine, New York, New York
| | | | - Himanshu Nagar
- Department of Radiation Oncology, Weill Cornell Medicine/NewYork-Presbyterian, New York, New York
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Abbruzzese L, Nescis E, Turco E, Amoroso P, Carluccio G. Efficacy of allogeneic platelet growth factors in actinic cystitis: The resolution of trouble? Transfus Apher Sci 2023; 62:103732. [PMID: 37263885 DOI: 10.1016/j.transci.2023.103732] [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: 12/14/2022] [Revised: 05/08/2023] [Accepted: 05/20/2023] [Indexed: 06/03/2023]
Abstract
BACKGROUND Actinic cystitis is a severe complication after radiotherapy for prostate cancer. It is a chronic inflammatory process that leads to an alteration of bladder mucosa with formation of petechiae and subsequently hematuria. Actinic cystitis responds poorly to medical treatment, with a heavy burden on patients' quality of life. Patients with refractory hematuria may undergo cystectomy in the attempt to control bleeding. We conducted a prospective study to evaluate the effectiveness of the allogeneic platelet growth factors for actinic cystitis. METHODS AND MATERIAL Nine patients with actinic cystitis were enrolled in this study. The primary outcome measures were the effects of the platelet growth factors on the injury of the bladder mucosa. The secondary outcome was the change in quality of life RESULTS: A total of 9 patients, mean age 68 (range 59-81) underwent a therapeutic program of bladder instillation with allogeneic platelets growth factors for 3 months. Of the 9 patients, all (100 %) had complete resolution of hematuria and urinary symptoms. After three months cystoscopy showed regeneration of the normal bladder mucosa. Biopsies allowed histological confirmation of the finding. DISCUSSION The instillation of allogeneic platelet growth factors in actinic cystitis is a new treatment that in this setting of patients appears promising in promoting a resolution of urinary symptoms, hematuria and avoiding a disabling surgery such as cystectomy.
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Affiliation(s)
- Luciano Abbruzzese
- Service of Immunohaematology and Transfusion Centre, Hospital Cardinal G. Panico, Tricase, Italy.
| | - Elisa Nescis
- Service of Immunohaematology and Transfusion Centre, Hospital Cardinal G. Panico, Tricase, Italy
| | - Elisabetta Turco
- Service of Immunohaematology and Transfusion Centre, Hospital Cardinal G. Panico, Tricase, Italy
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13
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Brooks KA, Gross JH. Radiotherapy-induced Pathology of the Ear. Otolaryngol Clin North Am 2023; 56:977-985. [PMID: 37414656 DOI: 10.1016/j.otc.2023.05.013] [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] [Indexed: 07/08/2023]
Abstract
Acute radiotherapy (RT)-induced external ear soft tissue changes start with erythema and dry desquamation and may progress to moist desquamation and epidermal ulceration. Chronic RT-induced changes include epithelial atrophy and subcutaneous fibrosis. Although RT-induced radiation dermatitis has been well studied, interventions for soft tissue disease involving the external auditory canal (EAC) warrant investigation. Medical management includes topical steroid treatment for EAC radiation dermatitis and topical antibiotic therapy for suppurative otitis externa. Hyperbaric oxygen and pentoxifylline-vitamin E therapy have shown promise for other applications, but their clinical effect on soft tissue EAC disease is currently undefined.
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Affiliation(s)
- Kaitlyn A Brooks
- Department of Otolaryngology-Head and Neck Surgery, Emory University, Atlanta, GA 30308, USA
| | - Jennifer H Gross
- Department of Otolaryngology-Head and Neck Surgery, Emory University, Atlanta, GA 30308, USA.
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14
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Momeni N, Ali Boroomand M, Roozmand Z, Namiranian N, Hamzian N. Normal tissue complication probability of acute eyelids erythema following radiotherapy of head and neck cancers and skull-base tumors. Phys Med 2023; 112:102621. [PMID: 37329741 DOI: 10.1016/j.ejmp.2023.102621] [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: 01/03/2023] [Revised: 06/04/2023] [Accepted: 06/06/2023] [Indexed: 06/19/2023] Open
Abstract
PURPOSE Radiation therapy is broadly used as one of the main treatment methods for patients with head and neck cancers and skull base tumors. However, it can lead to normal tissue complications. Therefore, this study aimed to model normal tissue complication probability (NTCP) of eyelid skin erythema after radiation therapy. METHODS The dataset of 45 patients with head and neck and skull base tumors was prospectively collected from their dose-volume histograms (DVHs). Grade 1 + eyelid skin erythema based on the Common Terminology Criteria for Adverse Events (CTCAE 4.0) was evaluated as the endpoint after a three-month follow-up. The Lyman-Kutcher-Burman (LKB) radiobiological model was developed based on generalized equivalent uniform dose (gEUD). Model parameters were calculated by maximum likelihood estimation. Model performance was evaluated by ROC-AUC, Brier score and Hosmer-Lemeshow test. RESULTS After three months of follow-up, 13.33% of patients experienced eyelids skin erythema grade 1 or more. The parameters of the LKB model were: TD50 = 30 Gy, m = 0.14, and n = 0.10. The model showed good predictive performance with ROC-AUC = 0.80 (CI:0.66-0.94) and a Brier score of 0.20. CONCLUSIONS In this study, NTCP of eyelid skin erythema was modeled based on the LKB radiobiological model with good predictive performance.
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Affiliation(s)
- Nastaran Momeni
- Department of Medical Physics, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Mohammad Ali Boroomand
- Clinical oncology department, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Zahra Roozmand
- Department of Medical Physics, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Nasim Namiranian
- Diabetes research center of Alikhani, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Nima Hamzian
- Department of Medical Physics, School of Medicine, Shahid Sadoughi Universi of Medical Sciences, Yazd, Iran.
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15
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Lee JW, Chung MJ. Prostate only radiotherapy using external beam radiotherapy: A clinician's perspective. World J Clin Cases 2022; 10:10428-10434. [PMID: 36312490 PMCID: PMC9602254 DOI: 10.12998/wjcc.v10.i29.10428] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2022] [Revised: 08/12/2022] [Accepted: 08/30/2022] [Indexed: 02/05/2023] Open
Abstract
Prostate-only radiotherapy (PORT) is widely used as the definitive treatment for localized prostate cancer. Prostate cancer has an α/β ratio; therefore, radiotherapy (RT) with a large fraction size is biologically effective for tumor control. The current external beam RT technique for PORT has been improved from three-dimensional conformal RT to intensity-modulated, stereotactic body, and image-guided RTs. These methods are associated with reduced radiation exposure to normal tissues, decreasing urinary and bowel toxicity. Several trials have shown improved local control with dose escalation through the aforementioned methods, and the efficacy and safety of intensity-modulated and stereotactic body RTs have been proven. However, the management of RT in patients with prostate cancer has not been fully elucidated. As a clinician, there are several concerns regarding the RT volume and dose considering the patient's age and comorbidities. Therefore, this review aimed to discuss the radiobiological basis and external beam technical advancements in PORT for localized prostate cancer from a clinician's perspective.
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Affiliation(s)
- Jeong Won Lee
- Department of Radiation Oncology, Daegu Catholic University School of Medicine, Daegu 42472, South Korea
| | - Mi Joo Chung
- Department of Radiation Oncology, Hanyang University Hanmaeum Changwon Hospital, Changwon 51139, South Korea
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16
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Beijer JGM, Teepen JC, Streefkerk N, Heijnen RM, Janssens GO, Kremer LCM, van Dalen EC, Ronckers CM. Late Toxicity After 3-Dimensional External Beam Radiotherapy Among Children With Cancer: A Systematic Review. J Pediatr Hematol Oncol 2022; 44:117-134. [PMID: 35398857 DOI: 10.1097/mph.0000000000002445] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Accepted: 02/03/2022] [Indexed: 11/26/2022]
Abstract
Radiotherapy has evolved from 2-dimensional conventional radiotherapy (2D-RT) to 3-dimensional planned radiotherapy (3D-RT). Because 3D-RT improves conformity, an altered late health outcomes risk profile is anticipated. Here, we systematically reviewed the current literature on late toxicity after 3D-RT in children treated for cancer. PubMed was searched for studies describing late toxicity after 3D-RT for childhood cancer (below 21 y). Late toxicity was defined as somatic health outcomes occurring ≥90 days after treatment. We identified 13 eligible studies, describing most frequently head/neck area tumors. Included studies reported on crude frequencies of late toxicities including subsequent tumors and conditions of organ systems. Three studies offered a global assessment of the full spectrum of late toxicity; one study compared toxicities after 2D-RT and 3D-RT. Incidence rates were typically not provided. Heterogeneity in study characteristics, small study sizes and short follow-up times precluded multivariable modeling and pooling of data. In conclusion, among the first pediatric cohorts treated with 3D-RT, a broad variety of late toxicity is reported; precise estimates of incidence, and contributions of risk factors are unclear. Continued systematic evaluation of well-defined health outcomes in survivors treated with 3D-RT, including proton therapy, is needed to optimize evidence-based care for children with cancer and survivors.
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Affiliation(s)
| | | | | | | | - Geert O Janssens
- Princess Máxima Center for Pediatric Oncology
- Department of Radiation Oncology, University Medical Center Utrecht, Utrecht
| | - Leontien C M Kremer
- Princess Máxima Center for Pediatric Oncology
- Department of Pediatrics, Emma Children's Hospital, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands
| | | | - Cécile M Ronckers
- Princess Máxima Center for Pediatric Oncology
- Brandenburg Medical School, Institute of Biostatistics and Registry Research, Neuruppin, Germany
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17
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Liu Z, Jiang S, Tian Y, Shang H, Chen K, Tan H, Zhang L, Jing H, Cheng W. Targeted Phototherapy by Niobium Carbide for Mammalian Tumor Models Similar to Humans. Front Oncol 2022; 12:827171. [PMID: 35223508 PMCID: PMC8866440 DOI: 10.3389/fonc.2022.827171] [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: 12/01/2021] [Accepted: 01/17/2022] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND In the past few decades, nanomaterial-mediated phototherapy has gained significant attention as an alternative antitumor strategy. However, its antitumor success is majorly limited to the treatment of subcutaneous tumors in nude mice. In fact, no studies have been previously conducted in this area/field on clinically-relevant big animal models. Therefore, there is an urgent need to conduct further investigation in a typical big animal model, which is more closely related to the human body. RESULTS In this study, niobium carbide (NbC) was selected as a photoactive substance owing to the presence of outstanding near-infrared (NIR) absorption properties, which are responsible for the generation of NIR-triggered hyperthermia and reactive oxygen species that contribute towards synergetic photothermal and photodynamic effect. Moreover, the present study utilized macrophages as bio-carrier for the targeted delivery of NbC, wherein phagocytosis by macrophages retained the photothermal/photodynamic effect of NbC. Consequently, macrophage-loaded NbC ensured/allowed complete removal of solid tumors both in nude mice and big animal models involving rabbits. Meanwhile, two-dimensional ultrasound, shave wave elastography (SWE), and contrast-enhanced ultrasound (CEUS) were used to monitor physiological evolution in tumor in vivo post-treatment, which clearly revealed the occurrence of the photoablation process in tumor and provided a new strategy for the surveillance of tumor in big animal models. CONCLUSION Altogether, the use of a large animal model in this study presented higher clinical significance as compared to previous studies.
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Affiliation(s)
- Zhao Liu
- Department of Ultrasound, Harbin Medical University Cancer Hospital, Harbin, China
| | - Shan Jiang
- Department of Ultrasound, Harbin Medical University Cancer Hospital, Harbin, China
| | - Yuhang Tian
- Department of Ultrasound, Harbin Medical University Cancer Hospital, Harbin, China
| | - Haitao Shang
- Department of Ultrasound, Harbin Medical University Cancer Hospital, Harbin, China
| | - Kexin Chen
- Department of Pathology, Harbin Medical University Cancer Hospital, Harbin, China
| | - Haoyan Tan
- Department of Ultrasound, Harbin Medical University Cancer Hospital, Harbin, China
| | - Lei Zhang
- Department of Ultrasound, Harbin Medical University Cancer Hospital, Harbin, China
| | - Hui Jing
- Department of Ultrasound, Harbin Medical University Cancer Hospital, Harbin, China
| | - Wen Cheng
- Department of Ultrasound, Harbin Medical University Cancer Hospital, Harbin, China
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18
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Takenaka M, Hosono M, Rehani MM, Chiba Y, Ishikawa R, Okamoto A, Yamazaki T, Nakai A, Omoto S, Minaga K, Kamata K, Yamao K, Hayashi S, Nishida T, Kudo M. Comparison of radiation exposure between endoscopic ultrasound-guided drainage and transpapillary drainage by endoscopic retrograde cholangiopancreatography for pancreatobiliary diseases. Dig Endosc 2022; 34:579-586. [PMID: 34107099 PMCID: PMC9292288 DOI: 10.1111/den.14060] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2021] [Revised: 05/24/2021] [Accepted: 06/08/2021] [Indexed: 02/08/2023]
Abstract
OBJECTIVES The transpapillary drainage by endoscopic retrograde cholangiopancreatography (ERCP-D) cannot be performed without fluoroscopy, and there are many situations in which fluoroscopy is required even in endoscopic ultrasound-guided drainage (EUS-D). Previous studies have compared the efficacy, but not the radiation exposure of EUS-D and ERCP-D. While radiation exposure in ERCP-D has been previously evaluated, there is a paucity of information regarding radiation doses in EUS-D. This study aimed to assess radiation exposure in EUS-D compared with that in ERCP-D. METHODS This retrospective single-center cohort study included consecutive patients who underwent EUS-D and ERCP-D between October 2017 and March 2019. The air kerma (AK, mGy), kerma-area product (KAP, Gycm2 ), fluoroscopy time (FT, min), and procedure time (PT, min) were assessed. The invasive probability weighting method was used to qualify the comparisons. RESULTS We enrolled 372 and 105 patients who underwent ERCP-D and EUS-D, respectively. The mean AK, KAP, and FT in the EUS-D group were higher by 53%, 28%, and 27%, respectively, than those in the ERCP-D group, whereas PT was shorter by approximately 11% (AK, 135.0 vs. 88.4; KAP, 28.1 vs. 21.9; FT, 20.4 vs. 16.0; PT, 38.7 vs. 43.5). The sub-analysis limited to biliary drainage cases showed the same trend (AK, 128.3 vs. 90.9; KAP, 27.0 vs. 22.2; FT, 16.4 vs. 16.1; PT, 32.5 vs. 44.4). CONCLUSIONS This is the first study to assess radiation exposure in EUS-D compared with that in ERCP-D. Radiation exposure was significantly higher in EUS-D than in ERCP-D, despite the shorter procedure time.
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Affiliation(s)
- Mamoru Takenaka
- Departments ofGastroenterology and HepatologyKindai University Faculty of MedicineOsakaJapan
| | - Makoto Hosono
- Department ofRadiologyKindai University Faculty of MedicineOsakaJapan
| | - Madan M. Rehani
- Global Outreach for Radiation Protection ProgramRadiation Safety CommitteeMassachusetts General HospitalBostonUSA
| | - Yasutaka Chiba
- Clinical Research CenterKindai University HospitalOsakaJapan
| | - Rei Ishikawa
- Departments ofGastroenterology and HepatologyKindai University Faculty of MedicineOsakaJapan
| | - Ayana Okamoto
- Departments ofGastroenterology and HepatologyKindai University Faculty of MedicineOsakaJapan
| | - Tomohiro Yamazaki
- Departments ofGastroenterology and HepatologyKindai University Faculty of MedicineOsakaJapan
| | - Atsushi Nakai
- Departments ofGastroenterology and HepatologyKindai University Faculty of MedicineOsakaJapan
| | - Shunsuke Omoto
- Departments ofGastroenterology and HepatologyKindai University Faculty of MedicineOsakaJapan
| | - Kosuke Minaga
- Departments ofGastroenterology and HepatologyKindai University Faculty of MedicineOsakaJapan
| | - Ken Kamata
- Departments ofGastroenterology and HepatologyKindai University Faculty of MedicineOsakaJapan
| | - Kentaro Yamao
- Departments ofGastroenterology and HepatologyKindai University Faculty of MedicineOsakaJapan
| | - Shiro Hayashi
- Department of GastroenterologyToyonaka Municipal HospitalOsakaJapan,Department of Gastroenterology and Internal MedicineHayashi ClinicOsakaJapan
| | - Tsutomu Nishida
- Department of GastroenterologyToyonaka Municipal HospitalOsakaJapan
| | - Masatoshi Kudo
- Departments ofGastroenterology and HepatologyKindai University Faculty of MedicineOsakaJapan
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Hall WA, Paulson E, Li XA, Erickson B, Schultz C, Tree A, Awan M, Low DA, McDonald BA, Salzillo T, Glide-Hurst CK, Kishan AU, Fuller CD. Magnetic resonance linear accelerator technology and adaptive radiation therapy: An overview for clinicians. CA Cancer J Clin 2022; 72:34-56. [PMID: 34792808 PMCID: PMC8985054 DOI: 10.3322/caac.21707] [Citation(s) in RCA: 51] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2021] [Revised: 09/01/2021] [Accepted: 09/22/2021] [Indexed: 12/25/2022] Open
Abstract
Radiation therapy (RT) continues to play an important role in the treatment of cancer. Adaptive RT (ART) is a novel method through which RT treatments are evolving. With the ART approach, computed tomography or magnetic resonance (MR) images are obtained as part of the treatment delivery process. This enables the adaptation of the irradiated volume to account for changes in organ and/or tumor position, movement, size, or shape that may occur over the course of treatment. The advantages and challenges of ART maybe somewhat abstract to oncologists and clinicians outside of the specialty of radiation oncology. ART is positioned to affect many different types of cancer. There is a wide spectrum of hypothesized benefits, from small toxicity improvements to meaningful gains in overall survival. The use and application of this novel technology should be understood by the oncologic community at large, such that it can be appropriately contextualized within the landscape of cancer therapies. Likewise, the need to test these advances is pressing. MR-guided ART (MRgART) is an emerging, extended modality of ART that expands upon and further advances the capabilities of ART. MRgART presents unique opportunities to iteratively improve adaptive image guidance. However, although the MRgART adaptive process advances ART to previously unattained levels, it can be more expensive, time-consuming, and complex. In this review, the authors present an overview for clinicians describing the process of ART and specifically MRgART.
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MESH Headings
- History, 20th Century
- History, 21st Century
- Humans
- Magnetic Resonance Imaging, Interventional/history
- Magnetic Resonance Imaging, Interventional/instrumentation
- Magnetic Resonance Imaging, Interventional/methods
- Magnetic Resonance Imaging, Interventional/trends
- Neoplasms/diagnostic imaging
- Neoplasms/radiotherapy
- Particle Accelerators
- Radiation Oncology/history
- Radiation Oncology/instrumentation
- Radiation Oncology/methods
- Radiation Oncology/trends
- Radiotherapy Planning, Computer-Assisted/history
- Radiotherapy Planning, Computer-Assisted/instrumentation
- Radiotherapy Planning, Computer-Assisted/methods
- Radiotherapy Planning, Computer-Assisted/trends
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Affiliation(s)
- William A. Hall
- Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Eric Paulson
- Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - X. Allen Li
- Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Beth Erickson
- Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Christopher Schultz
- Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Alison Tree
- The Royal Marsden National Health Service Foundation Trust and the Institute of Cancer Research, London, United Kingdom
| | - Musaddiq Awan
- Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Daniel A. Low
- Department of Radiation Oncology, University of California-Los Angeles, Los Angeles, California
| | - Brigid A. McDonald
- Department of Radiation Oncology, The University of Texas, MD Anderson Cancer Center, Houston, Texas
| | - Travis Salzillo
- Department of Radiation Oncology, The University of Texas, MD Anderson Cancer Center, Houston, Texas
| | - Carri K. Glide-Hurst
- Department of Radiation Oncology, University of Wisconsin-Madison, Madison, Wisconsin
| | - Amar U. Kishan
- Department of Radiation Oncology, University of California-Los Angeles, Los Angeles, California
| | - Clifton D. Fuller
- Department of Radiation Oncology, The University of Texas, MD Anderson Cancer Center, Houston, Texas
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Radiation Proctitis: The Potential Role of Hyaluronic Acid in the Prevention and Restoration of Any Damage to the Rectal Mucosa among Prostate Cancer Patients Submitted to Curative External Beam Radiotherapy. GASTROENTEROLOGY INSIGHTS 2021. [DOI: 10.3390/gastroent12040043] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Aim: To evaluate if hyaluronic acid reduces proctitis episodes with respect to corticosteroids in prostate cancer patients submitted to radical or adjuvant radiotherapy. Methods: A consecutive series of eligible patients received hyaluronic acid enemas as supportive care (experimental group, from January 2013 to June 2015). A historical group (control group), treated from October 2011 to December 2012, received beclomethasone dipropionate suppositories. We registered each patient’s data regarding acute and chronic proctitis. All patients were treated with static-intensity-modulated radiotherapy coupled to a daily set-up verification with orthogonal anterior–posterior/lateral X-ray pairs. Results: A total of 269 patients, 175 in the experimental group and 94 in the control group, was evaluated; 2 Gy/day (up to a total median dose of 80 Gy) and 2.7 Gy/day (up to a total median dose of 67.5 Gy) fractionation schemes were used for 216 and 53 patients, respectively. All patients had a good tolerance to radiotherapy, reporting no G3 or greater proctitis. No significant difference was reported concerning the total rate of proctitis between the two groups but only with respect to its grade: a higher G2 rate within the control group. There was no correlation between daily dose fractionation and toxicity grade. Conclusions: Hyaluronic acid enemas might be effective in reducing the severity of radiation proctitis.
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21
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Viani GA, Gouveia AG, Jacinto AA, Moraes FY. Stereotactic Body Radiotherapy for Prostate Cancer: Where, When, and Who? A Bibliometric Analysis. Am J Clin Oncol 2021; 44:553-558. [PMID: 34618725 DOI: 10.1097/coc.0000000000000869] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
OBJECTIVES To provide an overview of the achievements and future research with stereotactic body radiotherapy (SBRT) in prostate cancer. METHODS SBRT publications for prostate cancer were retrieved from the Web of Science and Dimension database. Bibliometric analyses were performed using VOSviewer and Prism graph. Analysis of variance test was used to compare the publication, citation, and the mean citation between specialty journals. Network maps were produced to identify authors' and countries' collaboration clusters. RESULTS Between 2006 and 2020, 574 publications fulfilling the inclusion criteria were identified, and a significant growth trend in publication (P<0.0001) and citation (P=0.001) number was recognized over the period. The United States was the most productive country with 253 (44.2%) articles. The RED Journal had the highest number of publications (14%) and citations (19%). Urology journals published (P=0.01) and cited significantly less than radiation oncology journals (P=0.01). All open access and non-open access number of publications increased over time, with a significant difference between non-open access and open access journals (P<0.0001). Two author clusters were identified, in the United States with the collaboration of Canadian and British authors, and in Italy with the participation of European authors. CONCLUSION The number of publications and citations on SBRT for prostate cancer has grown linearly in the last decades. The United States is the leading country in this research field, and the use of SBRT in oligometastatic disease, reirradiation, and salvage seems to be hot topics in this research field.
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Affiliation(s)
- Gustavo A Viani
- Department of Medical Imagings, Hematology and Oncology of University of São Paulo (FMRP-USP), Ribeirão Preto Medical School, Ribeirão Preto
| | - Andre G Gouveia
- Radiation Oncology Department, Américas Centro de Oncologia Integrado, Rio de Janeiro, RJ, Brazil
| | | | - Fabio Y Moraes
- Division of Radiation Oncology, Department of Oncology, Kingston General Hospital, Queen's University, Kingston, ON, Canada
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22
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Kim D, Han W, Chang JH, Lee HJ. PMP(Porphyrin-Micelle-PSMA) Nanoparticles for Photoacoustic and Ultrasound Signal Amplification in Mouse Prostate Cancer Xenografts. Pharmaceutics 2021; 13:1636. [PMID: 34683929 PMCID: PMC8537944 DOI: 10.3390/pharmaceutics13101636] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2021] [Revised: 09/19/2021] [Accepted: 09/29/2021] [Indexed: 11/16/2022] Open
Abstract
Photoacoustic (PA) imaging is used widely in cancer diagnosis. However, the availability of PA agents has not made great progress due to the limitations of the one currently in use, porphyrin. Porphyrin-Micelle (PM), developed by synthesizing porphyrin and PEG-3.5k, confirmed the amplification of the PA agent signal, and added binding affinity in an LNCaP model by attaching prostate-specific membrane antigen PSMA. Compared to the previously used porphyrin, a superior signal was confirmed, and the potential of PMP was confirmed when it showed a signal superior to that of hemoglobin at the same concentration. In addition, in the in vivo mouse experiment, it was confirmed that the signal in the LNCaP xenograft model was stronger than that in the PC-3 xenograft model, and the PMP signal was about three times higher than that of PM and porphyrin.
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Affiliation(s)
- Daehyun Kim
- Department of Nano Science and Technology, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 08826, Korea;
- Department of Radiology, Seoul National University Bundang Hospital, 82 Gumi-ro 173, Bundang-gu, Seongnam 13620, Korea
- IMGT Co., Ltd., Seongnam 13605, Korea
| | - Wonkook Han
- Department of Information and Communication Engineering, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu 42988, Korea;
| | - Jin Ho Chang
- Department of Information and Communication Engineering, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu 42988, Korea;
| | - Hak Jong Lee
- Department of Nano Science and Technology, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 08826, Korea;
- Department of Radiology, Seoul National University Bundang Hospital, 82 Gumi-ro 173, Bundang-gu, Seongnam 13620, Korea
- IMGT Co., Ltd., Seongnam 13605, Korea
- Bio-MAX Institute, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Korea
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23
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Takenaka M, Hosono M, Hayashi S, Nishida T, Kudo M. The radiation doses and radiation protection on the endoscopic retrograde cholangiopancreatography procedures. Br J Radiol 2021; 94:20210399. [PMID: 34379457 DOI: 10.1259/bjr.20210399] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Although many interventions involving radiation exposure have been replaced to endoscopic procedure in the gastrointestinal and hepatobiliary fields, there remains no alternative for enteroscopy and endoscopic retrograde cholangiopancreatography (ERCP), which requires the use of radiation. In this review, we discuss the radiation doses and protective measures of endoscopic procedures, especially for ERCP. For the patient radiation dose, the average dose area product for diagnostic ERCP was 14-26 Gy.cm², while it increased to as high as 67-89 Gy.cm² for therapeutic ERCP. The corresponding entrance skin doses for diagnostic and therapeutic ERCP were 90 and 250 mGy, respectively. The mean effective doses were 3- 6 mSv for diagnostic ERCP and 12-20 mSv for therapeutic ERCP. For the occupational radiation dose, the typical doses were 94 μGy and 75 μGy for the eye and neck, respectively. However, with an over-couch-type X-ray unit, the eye and neck doses reached as high as 550 and 450 μGy, with maximal doses of up to 2.8 and 2.4 mGy/procedure, respectively.A protective lead shield was effective for an over couch X-ray tube unit. It lowered scattered radiation by up to 89.1% in a phantom study. In actual measurements, the radiation exposure of the endoscopist closest to the unit was reduced to approximately 12%. In conclusion, there is a clear need for raising awareness among medical personnel involved endoscopic procedures to minimise radiation risks to both the patients and staff.
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Affiliation(s)
- Mamoru Takenaka
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka-sayama, Japan
| | - Makoto Hosono
- Department of Radiation Oncology, Kindai University Faculty of Medicine, Osaka-sayama, Japan
| | - Shiro Hayashi
- Department of Gastroenterology, Toyonaka Municipal Hospital, Toyonaka, Japan.,Department of Gastroenterology and Internal Medicine, Hayashi Clinic, Suita, Japan
| | - Tsutomu Nishida
- Department of Gastroenterology, Toyonaka Municipal Hospital, Toyonaka, Japan
| | - Masatoshi Kudo
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka-sayama, Japan
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A new method for risk factor assessment of organs at risk including conformity index in radiotherapy treatment plan. JOURNAL OF RADIOTHERAPY IN PRACTICE 2021. [DOI: 10.1017/s1460396920000205] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
AbstractIntroduction:A comprehensive analysing method has been required since long in the field of radiotherapy. The basic purpose of all techniques has been to deliver the prescribed dose safely to the target volume containing tumour and as well as to reduce dose to organs at risk (OARs). The detailed comparison between different treatment techniques is very difficult and inexplicit as well. The gradual improvement in imaging software has made easy to users to assess spatial arrangement of tumour, critical organs and isodose lines in the form of a single 3D representation that can be observed from all angles. The conformity index (CI) alone cannot provide practical information about treatment plans as it is a single isodose line quantity.Aim:The aim of this study was to develop a new method to assess the degree of damage numerically for OARs along with CI assessment for the target.Materials and Methods:The radiotherapy plans of 30 patients of different sites, diagnosed as cancer, were selected for this study irrespective of gender. Out of 30 cases, 8 plans were of head and neck, 2 were of glyoblastoma (GBM), 10 were of pelvis, 5 were of left breast and other 5 were of oesophagus cancer. The mean age was 42 years ranging from 31 to 72 years. Patient’s consents were taken before starting the treatment and carried out this research. Risk factor (RF) for OARs depends on volume of irradiation (VVOI), total volume of the organ (VTVO) and tolerance dose (DTDO). All radiotherapy plans (Intensity Modulated Radiotherapy (IMRT) and Volumetric Modulated Arc Therapy (VMAT)) were generated using eclipse planning system, version 11.0 (Varian Medical System, Palo Alto, California, USA).Result:The formula developed to assess degree of damage of OARs including CI of the target is risk factor conformity index (RFC) = CI + RF. In head and neck cases, for right parotid, the maximum value of RF is 1·50 and minimum value is observed as 0·97. Optic nerve, brainstem and spinal cord are completely safe as their RF values are found to be 0 on RF scale.Conclusion:RFC is a comprehensive evaluation tool encompassing a wider range of clinically relevant parameters, isodose volumes and tolerance dose of OARs. It is an advance analysing method to check both the qualitative and quantitative nature of a conformal plan, and at the same time, it assesses the degree of damage of OARs.If RF ≥ 1, then OAR will be completely damaged as a result of irradiation.If RF = 0, then OAR will remain safe totally during the course of irradiation.
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25
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Furtado FS, Furtado GB, Oliveira AT, Oliveira FAA, Pinho CS, Sampaio JPA, Feitosa AML, de Lima Herculano Junir JR. Endorectal formalin instillation or argon plasma coagulation for hemorrhagic radiation proctopathy therapy: a prospective and randomized clinical trial. Gastrointest Endosc 2021; 93:1393-1400. [PMID: 33220297 DOI: 10.1016/j.gie.2020.11.007] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2020] [Accepted: 11/09/2020] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS Radiotherapy may cause hemorrhagic radiation proctopathy (HRP). For conservative treatment of refractory HRP, argon plasma coagulation (APC) is the first-choice therapy. Endorectal formalin instillation (EFI), in turn, is an attractive treatment option because of its satisfactory results, great availability, and low cost. Nevertheless, comparative studies between these procedures are rather scarce. This study aims to make a prospective and randomized comparison of the outcomes in 2 HRP patient groups treated with either APC or EFI. METHODS Twenty-seven patients (11 women), with a mean age of 67 years (range, 36-83), were randomized to receive either APC (n = 14) or EFI (n = 13). On completion of the treatment, comparisons were made in relation to the baseline for each patient and between groups for endoscopic findings according to the Vienna score and the telangiectasia distribution pattern score (TDP); the impact of radiation proctitis on patients' lives was made according to the modified radiation toxicity score (MRTS) and hemoglobin levels. Number of sessions, duration of therapy, and adverse events were also compared between groups. The endoscopic therapeutic success (ETS) was defined by the absence or only few residual telangiectasias (TDP ≤1) on conclusion. RESULTS An ETS of 92.8% was achieved in patients treated with APC and 92.3% for those treated with EFI (P > .05); there was an MRTS improvement of 85.7% in APC patients and 69.2% in EFI patients (P > .05). Mild adverse events occurred, respectively, in 23% and 28.5% in the EFI and APC groups (P > .05). CONCLUSIONS The study showed that APC and EFI have similar efficacy and a high safety profile for HRP treatment. (Clinical trial registration number: 3.120.353.).
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Affiliation(s)
- Flávia S Furtado
- Service of Digestive Endoscopy, General Hospital of Fortaleza (affiliated with the Unified Brazilian National Health System), Fortaleza, Brazil
| | - Gildo B Furtado
- Service of Digestive Endoscopy, General Hospital of Fortaleza (affiliated with the Unified Brazilian National Health System), Fortaleza, Brazil
| | - Alessandrino T Oliveira
- Service of Digestive Endoscopy, General Hospital of Fortaleza (affiliated with the Unified Brazilian National Health System), Fortaleza, Brazil
| | - Francisco A A Oliveira
- Service of Digestive Endoscopy, General Hospital of Fortaleza (affiliated with the Unified Brazilian National Health System), Fortaleza, Brazil
| | - Cibele S Pinho
- Service of Digestive Endoscopy, General Hospital of Fortaleza (affiliated with the Unified Brazilian National Health System), Fortaleza, Brazil
| | - João P A Sampaio
- Service of Digestive Endoscopy, General Hospital of Fortaleza (affiliated with the Unified Brazilian National Health System), Fortaleza, Brazil
| | - Ana M L Feitosa
- Service of Digestive Endoscopy, General Hospital of Fortaleza (affiliated with the Unified Brazilian National Health System), Fortaleza, Brazil
| | - José Ruver de Lima Herculano Junir
- Service of Digestive Endoscopy, General Hospital of Fortaleza (affiliated with the Unified Brazilian National Health System), Fortaleza, Brazil
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He M, Yang T, Wang Y, Wang M, Chen X, Ding D, Zheng Y, Chen H. Immune Checkpoint Inhibitor-Based Strategies for Synergistic Cancer Therapy. Adv Healthc Mater 2021; 10:e2002104. [PMID: 33709564 DOI: 10.1002/adhm.202002104] [Citation(s) in RCA: 51] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2020] [Revised: 01/26/2021] [Indexed: 12/16/2022]
Abstract
Immune checkpoint blockade therapy (ICBT) targeting checkpoints, such as, cytotoxic T-lymphocyte associated protein-4 (CTLA-4), programmed death-1 (PD-1), or programmed death-ligand 1 (PD-L1), can yield durable immune response in various types of cancers and has gained constantly increasing research interests in recent years. However, the efficacy of ICBT alone is limited by low response rate and immune-related side effects. Emerging preclinical and clinical studies reveal that chemotherapy, radiotherapy, phototherapy, or other immunotherapies can reprogramm immunologically "cold" tumor microenvironment into a "hot" one, thus synergizing with ICBT. In this review, the working principle and current development of various immune checkpoint inhibitors are summarized, while the interactive mechanism and recent progress of ICBT-based synergistic therapies with other immunotherapy, chemotherapy, phototherapy, and radiotherapy in fundamental and clinical studies in the past 5 years are depicted and highlighted. Moreover, the potential issues in current studies of ICBT-based synergistic therapies and future perspectives are also discussed.
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Affiliation(s)
- Mengying He
- Jiangsu Key Laboratory of Neuropsychiatric Diseases College of Pharmaceutical Sciences Soochow University Suzhou 215123 China
| | - Tao Yang
- Jiangsu Key Laboratory of Neuropsychiatric Diseases College of Pharmaceutical Sciences Soochow University Suzhou 215123 China
| | - Yuhan Wang
- Jiangsu Key Laboratory of Neuropsychiatric Diseases College of Pharmaceutical Sciences Soochow University Suzhou 215123 China
| | - Mengyuan Wang
- Jiangsu Key Laboratory of Neuropsychiatric Diseases College of Pharmaceutical Sciences Soochow University Suzhou 215123 China
| | - Xingye Chen
- Jiangsu Key Laboratory of Neuropsychiatric Diseases College of Pharmaceutical Sciences Soochow University Suzhou 215123 China
| | - Dawei Ding
- Jiangsu Key Laboratory of Neuropsychiatric Diseases College of Pharmaceutical Sciences Soochow University Suzhou 215123 China
| | - Yiran Zheng
- Jiangsu Key Laboratory of Neuropsychiatric Diseases College of Pharmaceutical Sciences Soochow University Suzhou 215123 China
| | - Huabing Chen
- Jiangsu Key Laboratory of Neuropsychiatric Diseases College of Pharmaceutical Sciences Soochow University Suzhou 215123 China
- State Key Laboratory of Radiation Medicine and Protection Soochow University Suzhou 215123 China
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27
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Shi H, Suo Y, Zhang Z, Liu R, Liu H, Cheng Z. Copper(II)-disulfiram loaded melanin-dots for cancer theranostics. NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE 2020; 32:102340. [PMID: 33227540 DOI: 10.1016/j.nano.2020.102340] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/23/2020] [Revised: 11/02/2020] [Accepted: 11/11/2020] [Indexed: 12/24/2022]
Abstract
Copper(II) diethyldithiocarbamate complex (CuET), the metabolite of disulfiram complexed with copper, is the component responsible for cancer treatment efficacy of disulfiram. But the hydrophobic property of CuET limits its use in vivo, and an appropriate drug delivery system needs to be developed. Ultrasmall melanin nanoparticle (M-Dot) with excellent biosafety and biocompatibility properties has been synthesized in our previous studies. Herein we prepared CuET loaded with M-Dots through hydrophobic interaction, which could enhance the water solubility significantly. After the administration of M-Dots-CuET in mice tumor models, the nanoparticles showed good tumor accumulation as evidenced by the enhanced photoacoustic signal in tumor regions. M-Dots-CuET also displayed excellent tumor inhibition capability, and the tumor growth inhibition value (TGI) was 45.1%. When combined with photothermal therapy, the TGI reached up to 78.6%. In summary, M-Dots-CuET provide a new potential strategy for cancer theranostics.
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Affiliation(s)
- Hui Shi
- Institute of Molecular Medicine, College of Life and Health Sciences, Northeastern University, Shenyang, China
| | - Yongkuan Suo
- Institute of Molecular Medicine, College of Life and Health Sciences, Northeastern University, Shenyang, China
| | - Zhiling Zhang
- Institute of Molecular Medicine, College of Life and Health Sciences, Northeastern University, Shenyang, China
| | - Ruiqi Liu
- Institute of Molecular Medicine, College of Life and Health Sciences, Northeastern University, Shenyang, China
| | - Hongguang Liu
- Institute of Molecular Medicine, College of Life and Health Sciences, Northeastern University, Shenyang, China.
| | - Zhen Cheng
- Molecular Imaging Program at Stanford, Stanford University, Palo Alto, CA, USA.
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Andren J, Bennett MH. An observational trial to establish the effect of hyperbaric oxygen treatment on pelvic late radiation tissue injury due to radiotherapy. Diving Hyperb Med 2020; 50:250-255. [PMID: 32957127 DOI: 10.28920/dhm50.3.250-255] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2020] [Accepted: 06/09/2020] [Indexed: 12/25/2022]
Abstract
INTRODUCTION Rates of pelvic cancer are growing globally with around half of these patients receiving radiotherapy. In a small proportion, radiotherapy results in significant late radiation tissue injury (LRTI) to surrounding tissue, most commonly affecting the bladder and bowel mucosa. We conducted a combined prospective and retrospective observational trial to establish the effectiveness of hyperbaric oxygen treatment (HBOT) in improving the symptoms and signs of LRTI in these patients. METHODS Fifty-two patients were included after receiving radiotherapy for cancers of the bowel, bladder, cervix, prostate or vulva. They received HBOT at 203-243 kPa (2.0-2.4 atmospheres absolute (atm abs)) for 90 minutes with the median number of treatments being 30 (IQR 1). Late effects normal tissues - subjective, objective, management, analytic (LENT-SOMA) scores were recorded before and after treatment. RESULTS The mean LENT-SOMA scores before and after HBOT were 11.7 (SD 5.3) and 8.1 (5.1) respectively. This reduction in score of 3.7 (95% CI 2.6 to 4.8) was statistically significant (P < 0.001). For radiation cystitis the mean reduction was 3.7 (95% CI 2.4 to 5.0, P < 0.001) and for radiation proctitis was 3.8 (95% CI 1.4 to 6.1, P = 0.004). There were no significant adverse effects recorded. CONCLUSIONS Hyperbaric oxygen treatment may be an effective and safe treatment for pelvic late tissue radiation injury.
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Affiliation(s)
- James Andren
- Department of Diving and Hyperbaric Medicine, Prince of Wales Hospital, Sydney, Australia.,Corresponding author: Dr James Andren, 4 Adelaide Place, Canterbury CT1 2QA, England,
| | - Michael H Bennett
- Department of Diving and Hyperbaric Medicine, Prince of Wales Hospital, Sydney, Australia.,Prince of Wales Clinical School, University of New South Wales, Sydney, Australia
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29
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Mohler JL, Antonarakis ES, Armstrong AJ, D'Amico AV, Davis BJ, Dorff T, Eastham JA, Enke CA, Farrington TA, Higano CS, Horwitz EM, Hurwitz M, Ippolito JE, Kane CJ, Kuettel MR, Lang JM, McKenney J, Netto G, Penson DF, Plimack ER, Pow-Sang JM, Pugh TJ, Richey S, Roach M, Rosenfeld S, Schaeffer E, Shabsigh A, Small EJ, Spratt DE, Srinivas S, Tward J, Shead DA, Freedman-Cass DA. Prostate Cancer, Version 2.2019, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 2020; 17:479-505. [PMID: 31085757 DOI: 10.6004/jnccn.2019.0023] [Citation(s) in RCA: 884] [Impact Index Per Article: 176.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
The NCCN Guidelines for Prostate Cancer include recommendations regarding diagnosis, risk stratification and workup, treatment options for localized disease, and management of recurrent and advanced disease for clinicians who treat patients with prostate cancer. The portions of the guidelines included herein focus on the roles of germline and somatic genetic testing, risk stratification with nomograms and tumor multigene molecular testing, androgen deprivation therapy, secondary hormonal therapy, chemotherapy, and immunotherapy in patients with prostate cancer.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | | | | | - Joseph E Ippolito
- Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine
| | | | | | | | - Jesse McKenney
- Case Comprehensive Cancer Center/University Hospitals Seidman Cancer Center and Cleveland Clinic Taussig Cancer Institute
| | - George Netto
- University of Alabama at Birmingham Comprehensive Cancer Center
| | | | | | | | | | - Sylvia Richey
- St. Jude Children's Research Hospital/The University of Tennessee Health Science Center
| | - Mack Roach
- UCSF Helen Diller Family Comprehensive Cancer Center
| | | | - Edward Schaeffer
- Robert H. Lurie Comprehensive Cancer Center of Northwestern University
| | - Ahmad Shabsigh
- The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute
| | - Eric J Small
- UCSF Helen Diller Family Comprehensive Cancer Center
| | | | | | - Jonathan Tward
- Huntsman Cancer Institute at the University of Utah; and
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30
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Das SS, Alkahtani S, Bharadwaj P, Ansari MT, ALKahtani MDF, Pang Z, Hasnain MS, Nayak AK, Aminabhavi TM. Molecular insights and novel approaches for targeting tumor metastasis. Int J Pharm 2020; 585:119556. [PMID: 32574684 DOI: 10.1016/j.ijpharm.2020.119556] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2020] [Revised: 06/01/2020] [Accepted: 06/14/2020] [Indexed: 12/18/2022]
Abstract
In recent years, due to the effective drug delivery and preciseness of tumor sites or microenvironment, the targeted drug delivery approaches have gained ample attention for tumor metastasis therapy. The conventional treatment approaches for metastasis therapy have reported with immense adverse effects because they exhibited maximum probability of killing the carcinogenic cells along with healthy cells. The tumor vasculature, comprising of vasculogenic impressions and angiogenesis, greatly depends upon the growth and metastasis in the tumors. Therefore, various nanocarriers-based delivery approaches for targeting to tumor vasculature have been attempted as efficient and potential approaches for the treatment of tumor metastasis and the associated lesions. Furthermore, the targeted drug delivery approaches have found to be most apt way to overcome from all the limitations and adverse effects associated with the conventional therapies. In this review, various approaches for efficient targeting of pharmacologically active chemotherapeutics against tumor metastasis with the cohesive objectives of prognosis, tracking and therapy are summarized.
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Affiliation(s)
- Sabya Sachi Das
- Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi 835 215, Jharkhand, India
| | - Saad Alkahtani
- Department of Zoology, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia
| | - Priyanshu Bharadwaj
- UFR des Sciences de Santé, Université de Bourgogne Franche-Comté, Dijon 21000, France
| | - Mohammed Tahir Ansari
- School of Pharmacy, University of Nottingham Malaysia, Jalan Broga, Semenyih, Kajang, Selangor 43500, Malaysia
| | - Muneera D F ALKahtani
- Biology Department, College of Science, Princess Nourah bint Abdulrahman University, P.O. Box 102275, Riyadh 11675, Saudi Arabia
| | - Zhiqing Pang
- School of Pharmacy, Fudan University, Key Laboratory of Smart Drug Delivery, Ministry of Education, 826 Zhangheng Road, Shanghai 201203, China
| | - Md Saquib Hasnain
- Department of Pharmacy, Shri Venkateshwara University, NH-24, Rajabpur, Gajraula, Amroha 244236, U.P., India.
| | - Amit Kumar Nayak
- Department of Pharmaceutics, Seemanta Institute of Pharmaceutical Sciences, Mayurbhanj 757086, Odisha, India.
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Zheng K, Chen R, Sun Y, Tan Z, Liu Y, Cheng X, Leng J, Guo Z, Xu P. Cantharidin-loaded functional mesoporous titanium peroxide nanoparticles for non-small cell lung cancer targeted chemotherapy combined with high effective photodynamic therapy. Thorac Cancer 2020; 11:1476-1486. [PMID: 32246815 PMCID: PMC7262929 DOI: 10.1111/1759-7714.13414] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2020] [Revised: 03/14/2020] [Accepted: 03/15/2020] [Indexed: 02/01/2023] Open
Abstract
BACKGROUND Although photodynamic therapy (PDT) has emerged as a potential alternative to conventional chemotherapy, the low reactive oxygen species (ROS) yield of the photosensitizer such as TiO2 nanoparticles has limited its application. In addition, it is difficult to achieve effective tumor treatment with a single tumor therapy. METHODS We used TiOx nanocomposite (YSA-PEG-TiOX ) instead of TiO2 as a photosensitizer to solve the problem of insufficient ROS generation in PDT. Benefiting from the desired mesoporous structure of TiOx, Cantharidin (CTD), one of the active components of mylabris, is loaded into TiOx for targeted combination of chemotherapy and PDT. The cellular uptake in human non-small cell lung carcinoma cell line (A549) and human normal breast cell line (MCF 10A) was evaluated by confocal microscopy. in vitro cytotoxicity was evaluated using Cell Counting Kit-8 assay. The ROS was detected via a chemical probe DCFH-DA and the photodynamic treatment effect of YSA-PEG-TiOx was further evaluated by a living-dead staining. The cell apoptosis was detected by the flow cytometry. RESULTS Our findings showed that the modification of YSA peptide improved the cytotoxicity of YSA-PEG-TiOX /CTD to EphA2 overexpressing A549 non-small cell lung cancer (NSCLC) than non-YSA modified counterparts. In addition, TiOx generated adequate ROS under X-ray irradiation to further kill cancer cells. Flow analysis results also proved the superiority of this combined treatment. CONCLUSIONS YSA-PEG-TiOX nanoparticles could significantly increase ROS production under X-ray exposure and provide a new drug delivery nanocarrier for CTD in combination with PDT to achieve effective NSCLC treatment.
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Affiliation(s)
- Kun Zheng
- School of Life Science and MedicineDalian University of TechnologyPanjinChina
| | - Runze Chen
- School of Life Science and MedicineDalian University of TechnologyPanjinChina
| | - Yanxue Sun
- Department of Pharmaceutical Engineering, College of PharmacyInner Mongolia Medical UniversityHohhotChina
| | - Zhenquan Tan
- School of Petroleum and Chemical EngineeringDalian University of TechnologyPanjinChina
| | - Ye Liu
- School of Life Science and MedicineDalian University of TechnologyPanjinChina
| | - Xiao Cheng
- School of Life Science and MedicineDalian University of TechnologyPanjinChina
| | - Junke Leng
- School of Life Science and MedicineDalian University of TechnologyPanjinChina
| | - Zhaoming Guo
- School of Life Science and MedicineDalian University of TechnologyPanjinChina
| | - Pengcheng Xu
- Department of Pharmaceutical Engineering, College of PharmacyInner Mongolia Medical UniversityHohhotChina
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Lemelin V, Bass AD, Sanche L. Low energy (6-18 eV) electron scattering from condensed thymidine (dT) III: absolute electronic excitation cross sections. Phys Chem Chem Phys 2020; 22:8364-8372. [PMID: 32266899 DOI: 10.1039/d0cp00198h] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Absolute cross sections (CSs) for electronic excitation by low-energy electron (LEE) scattering, from condensed thymidine (dT) in the 6-18 eV incident energy range, were measured by high-resolution electron energy loss spectroscopy (HREELS). Various electron energy loss (EEL) spectra were acquired using 1 ML of dT condensed on a multilayer film of Ar held at about 20 K under ultra-high vacuum (∼1 × 10-11 Torr). dT is one of the most complex DNA constituents to be studied by HREELS and these spectra provide the first LEE energy-loss data for electronic excitation of a nucleoside. CSs for transitions to the states 13A', 13A'', 23A', 21A', 33A', 23A'', 43A', 33A'', 53A' and 51A' of dT were extracted from the EEL spectra. These states correlate to those previously measured for the thymine moiety. Two broad resonances are observed in the energy dependence of the CSs at around 8 and 10 eV; these energies are close to those found in earlier gas- and solid-phase studies on the interaction of LEEs with dT, thymine and related molecules. A quantitative comparison between the electronic CSs of dT and those of thymine and tetrahydrofuran indicates that no variation is induced in the electronic CSs of thymine upon chemically binding to a deoxyribose group.
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Affiliation(s)
- V Lemelin
- Groupe en Sciences des Radiations, Département de Médecine Nucléaire et Radiobiologie, Faculté de Médecine et Sciences des radiations, Université de Sherbrooke, Québec J1H 5N4, Canada.
| | - A D Bass
- Groupe en Sciences des Radiations, Département de Médecine Nucléaire et Radiobiologie, Faculté de Médecine et Sciences des radiations, Université de Sherbrooke, Québec J1H 5N4, Canada.
| | - L Sanche
- Groupe en Sciences des Radiations, Département de Médecine Nucléaire et Radiobiologie, Faculté de Médecine et Sciences des radiations, Université de Sherbrooke, Québec J1H 5N4, Canada.
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Mahase SS, D'Angelo D, Kang J, Hu JC, Barbieri CE, Nagar H. Trends in the Use of Stereotactic Body Radiotherapy for Treatment of Prostate Cancer in the United States. JAMA Netw Open 2020; 3:e1920471. [PMID: 32022878 DOI: 10.1001/jamanetworkopen.2019.20471] [Citation(s) in RCA: 59] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
IMPORTANCE Stereotactic body radiotherapy is a hypofractionated, cost-effective treatment option for localized prostate cancer. OBJECTIVE To characterize US national trends and the clinical and socioeconomic factors associated with the use of stereotactic body radiotherapy in prostate cancer. DESIGN, SETTING, AND PARTICIPANTS This retrospective cohort study used data collected by the National Cancer Database to assess the clinical and socioeconomic factors among 106 926 men diagnosed as having prostate cancer from 2010 to 2015 who underwent definitive radiotherapy and the trends in the use of this therapy. The initial analysis was performed between January and February 2018, with final updates performed August 2019. EXPOSURE Stereotactic body radiotherapy, defined as 5 fractions of radiotherapy. MAIN OUTCOMES AND MEASURES Temporal trends and clinical and sociodemographic factors associated with stereotactic body radiotherapy use. RESULTS In total, 106 926 patients diagnosed as having localized prostate cancer between 2010 and 2015 and receiving definitive radiotherapy were identified. White patients composed 77.3% of this cohort, whereas black patients composed 18.7%. Government-issued insurance was used by 61.2% of patients. More than 80% of patients had a Charlson-Deyo Comorbidity Index score of 0 (range, 0 to ≥3, with lower numbers indicating fewer comorbidities). In the study population, 25.7% had low-risk disease; 26.3%, favorable intermediate-risk disease; 23.3%, unfavorable intermediate-risk disease; and 24.7%, high-risk disease. The proportion of patients who underwent radiotherapy and received stereotactic body radiotherapy (a total of 5395 patients) increased from 3.1% in 2010 to 7.2% in 2015 (odds ratio, 0.36; 95% CI, 0.33-0.40; P < .001). Among the entire cohort, patients received a median dose of 36.25 Gy (range, 30.00-50.00 Gy). Androgen deprivation therapy use increased significantly as disease risk level increased among all patients receiving radiotherapy (9.5% with low risk to 76.6% with high risk; P = .02) and among those receiving stereotactic body radiotherapy (4.1% with low risk to 33.2% with high risk; P = .04) or not receiving stereotactic body radiotherapy (9.9% with low risk to 77.6% with high risk; P = .04). Patients treated at an academic center, living in an urban area, or possessing higher incomes and those who were healthier, white individuals, or were diagnosed as having lower-risk prostate cancer had higher odds of receiving stereotactic body radiotherapy. CONCLUSIONS AND RELEVANCE This study found that stereotactic body radiotherapy use in prostate cancer more than doubled from 2010 to 2015 but accounted for less than 10% of all patients undergoing radiotherapy. Androgen deprivation therapy use increased with disease risk among patients overall, regardless of receiving stereotactic body radiotherapy. Socioeconomic and clinical determinants of stereotactic body radiotherapy included risk category, Charlson-Deyo Comorbidity Index score, facility type and location, income, race/ethnicity, and year of diagnosis. These results are hypothesis generating; further studies evaluating potential disparities in stereotactic body radiotherapy use in localized prostate cancer are warranted.
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Affiliation(s)
- Sean S Mahase
- Department of Radiation Oncology, Weill Cornell Medicine, New York, New York
| | - Debra D'Angelo
- Division of Biostatistics and Epidemiology, Department of Healthcare Policy and Research, Weill Cornell Medicine, New York, New York
| | - Josephine Kang
- Department of Radiation Oncology, Weill Cornell Medicine, New York, New York
| | - Jim C Hu
- Department of Urology, Weill Cornell Medicine, New York, New York
| | | | - Himanshu Nagar
- Department of Radiation Oncology, Weill Cornell Medicine, New York, New York
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Radiotherapy of prostate cancer: impact of treatment characteristics on the incidence of second tumors. BMC Cancer 2020; 20:90. [PMID: 32013912 PMCID: PMC6998272 DOI: 10.1186/s12885-020-6581-5] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2019] [Accepted: 01/27/2020] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND It has been hypothesized that radiotherapy (RT) techniques delivering radiations to larger volumes (IMRT, VMAT) are potentially associated with a higher risk of second primary tumors. The aim of this study was to analyse the impact of RT technique (3D-CRT vs IMRT/VMAT) on the incidence of second tumors in prostate cancer (PCa) patients. METHODS A retrospective study on 2526 previously irradiated PCa patients was performed. Patients were treated with 3D-CRT (21.3%), IMRT (68.1%), or VMAT (10.6%). Second tumors incidence was analysed in 3 categories: pelvic, pelvic and abdominal, and "any site". The correlation with RT technique was analysed using log-rank test and Cox's proportional hazard method. RESULTS With a median follow-up of 72 months (range: 9-185), 92 (3.6%) cases of second tumors were recorded with 48 months (range: 9-152) median interval from RT. Actuarial 10-year second tumor free survival (STFS) was 87.3%. Ten-year STFS in patients treated with 3D-CRT and IMRT/VMAT was 85.8 and 84.5%, respectively (p: .627). A significantly higher 10-year cumulative incidence of second tumors in the pelvis was registered in patients treated with IMRT/VMAT compared to 3D-CRT (10.7% vs 6.0%; p: .033). The lower incidence of second pelvic cancers in patients treated with 3D-CRT was confirmed at multivariable analysis (HR: 2.42, 95%CI: 1.07-5.47, p: .034). CONCLUSIONS The incidence of second pelvic tumors after RT of PCa showed a significant correlation with treatment technique. Further analyses in larger series with prolonged follow-up are needed to confirm these results.
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Glyco-nanoparticles: New drug delivery systems in cancer therapy. Semin Cancer Biol 2019; 69:24-42. [PMID: 31870939 DOI: 10.1016/j.semcancer.2019.12.004] [Citation(s) in RCA: 41] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2019] [Revised: 11/28/2019] [Accepted: 12/02/2019] [Indexed: 12/24/2022]
Abstract
Cancer is known as one of the most common diseases that are associated with high mobility and mortality in the world. Despite several efforts, current cancer treatment modalities often are highly toxic and lack efficacy and specificity. However, the application of nanotechnology has led to the development of effective nanosized drug delivery systems which are highly selective for tumors and allow a slow release of active anticancer agents. Different Nanoparticles (NPs) such as the silicon-based nano-materials, polymers, liposomes and metal NPs have been designed to deliver anti-cancer drugs to tumor sites. Among different drug delivery systems, carbohydrate-functionalized nanomaterials, specially based on their multi-valent binding capacities and desirable bio-compatibility, have attracted considerable attention as an excellent candidate for controlled release of therapeutic agents. In addition, these carbohydrate functionalized nano-carriers are more compatible with construction of the intracellular delivery platforms like the carbohydrate-modified metal NPs, quantum dots, and magnetic nano-materials. In this review, we discuss recent research in the field of multifunctional glycol-nanoparticles (GNPs) intended for cancer drug delivery applications.
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Forslund M, Ottenblad A, Ginman C, Johansson S, Nygren P, Johansson B. Effects of a nutrition intervention on acute and late bowel symptoms and health-related quality of life up to 24 months post radiotherapy in patients with prostate cancer: a multicentre randomised controlled trial. Support Care Cancer 2019; 28:3331-3342. [PMID: 31758324 PMCID: PMC7256032 DOI: 10.1007/s00520-019-05182-5] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2019] [Accepted: 11/07/2019] [Indexed: 02/06/2023]
Abstract
Purpose Radiotherapy to the prostate gland and pelvic lymph nodes may cause acute and late bowel symptoms and diminish quality of life. The aim was to study the effects of a nutrition intervention on bowel symptoms and health-related quality of life, compared with standard care. Methods Patients were randomised to a nutrition intervention (n = 92) aiming to replace insoluble fibres with soluble and reduce intake of lactose, or a standard care group (n = 88) who were recommended to maintain their habitual diet. Bowel symptoms, health-related quality of life and intake of fibre and lactose-containing foods were assessed up to 24 months after radiotherapy completion. Multiple linear regression was used to analyse the effects of the nutrition intervention on bowel symptoms during the acute (up to 2 months post radiotherapy) and the late (7 to 24 months post radiotherapy) phase. Results Most symptoms and functioning worsened during the acute phase, and improved during the late phase in both the intervention and standard care groups. The nutrition intervention was associated with less blood in stools (p = 0.047), flatulence (p = 0.014) and increased loss of appetite (p = 0.018) during the acute phase, and more bloated abdomen in the late phase (p = 0.029). However, these associations were clinically trivial or small. Conclusions The effect of the nutrition intervention related to dietary fibre and lactose on bowel symptoms from pelvic RT was small and inconclusive, although some minor and transient improvements were observed. The results do not support routine nutrition intervention of this type to reduce adverse effects from pelvic radiotherapy. Electronic supplementary material The online version of this article (10.1007/s00520-019-05182-5) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Marina Forslund
- Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
| | - Anna Ottenblad
- Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden
- Department of Nutrition and Dietetics, Karolinska University Hospital, Stockholm, Sweden
| | - Claes Ginman
- Department of Clinical Oncology, Central Hospital, Karlstad, Sweden
| | - Silvia Johansson
- Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden
| | - Peter Nygren
- Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden
| | - Birgitta Johansson
- Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden
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Wang L, Zhang T, Huo M, Guo J, Chen Y, Xu H. Construction of Nucleus-Targeting Iridium Nanocrystals for Photonic Hyperthermia-Synergized Cancer Radiotherapy. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2019; 15:e1903254. [PMID: 31549785 DOI: 10.1002/smll.201903254] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/23/2019] [Revised: 08/18/2019] [Indexed: 06/10/2023]
Abstract
Prominent tumor-cell nucleus targeting of radiosensitizer substantially affects the therapeutic consequence of advanced tumor radiotherapy via lethal nucleus DNA damage. Herein, ultrasmall iridium nanocrystals (Ir NCs, <5 nm) are constructed for efficient tumor-specific photonic hyperthermia-synergized radiotherapy. To endow the NCs with qualified cell nucleus-targeting performance, polyethylene glycol (PEG)-modified Ir NCs are decorated with αv β3 integrin-targeting cyclic arginine-glycine-aspartic (c(RGDyC)), designated as RGD, peptides and human immunodeficiency virus-1 transactivator of transcription protein(TAT), respectively, facilitating the tumor-cell-membrane (with overexpressed αv β3 integrin) and cell-nucleus targeting. The formulated Ir-RGD-TAT (Ir-R/T) NCs are demonstrated to accumulate inside the nucleus of tumor cells and generate effective DNA lesions upon X-ray irradiation. Further in vivo evaluations verify the satisfactory carcinoma destruction performance against 4T1 tumor xenografts. Importantly, the intriguing photonic NIR adsorption of Ir-R/T NCs has enabled the hyperthermia therapeutics accompanied with photoacoustic imaging modalities, achieving clinically promising biocompatible multifunctional radiosensitized nanoplatforms for effective tumor therapeutics.
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Affiliation(s)
- Liying Wang
- Department of Medical Ultrasound, Shanghai Tenth People's Hospital, Ultrasound Research and Education Institute, Tongji University School of Medicine, Tongji University Cancer Center, 301 Middle Yanchang Rd, Shanghai, 200072, P. R. China
| | - Tingting Zhang
- Department of Ultrasound, Eastern Hepatobiliary Surgery Hospital (EHBH), Second Military Medical University, 225 Changhai Rd, Shanghai, 200438, P. R. China
- The 985 Hospital of PLA, 30 Qiaodong Rd, Taiyuan, 030001, P. R. China
| | - Minfeng Huo
- State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, 1295 Dingxi Rd, Shanghai, 200050, P. R. China
| | - Jia Guo
- Department of Ultrasound, Eastern Hepatobiliary Surgery Hospital (EHBH), Second Military Medical University, 225 Changhai Rd, Shanghai, 200438, P. R. China
| | - Yu Chen
- State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, 1295 Dingxi Rd, Shanghai, 200050, P. R. China
| | - Huixiong Xu
- Department of Medical Ultrasound, Shanghai Tenth People's Hospital, Ultrasound Research and Education Institute, Tongji University School of Medicine, Tongji University Cancer Center, 301 Middle Yanchang Rd, Shanghai, 200072, P. R. China
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Song Y, Wang H, Pan Y, Liu T. Investigating the Multi-Target Pharmacological Mechanism of Hedyotis diffusa Willd Acting on Prostate Cancer: A Network Pharmacology Approach. Biomolecules 2019; 9:E591. [PMID: 31600936 PMCID: PMC6843553 DOI: 10.3390/biom9100591] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2019] [Revised: 10/01/2019] [Accepted: 10/03/2019] [Indexed: 02/06/2023] Open
Abstract
Hedyotis diffusa Willd (HDW) is one of the most well-known herbs used in the treatment of prostate cancer. However, the potential mechanisms of its anti-tumor effects have not been fully explored. Here, we applied a network pharmacology approach to explore the potential mechanisms of HDW against prostate cancer (PCa). We obtained 14 active compounds from HDW and 295 potential PCa related targets in total to construct a network, which indicated that quercetin and ursolic acid served as the main ingredients in HDW. Mitogen-activated Protein Kinase 8 (MAPK8), Interleukin 6 (IL6), Vascular Endothelial Growth Factor A (VEGFA), Signal Transducer and Activator of Transcription 3 (STAT3), Jun Proto-Oncogene (JUN), C-X-C Motif Chemokine Ligand 8 (CXCL8), Interleukin-1 Beta (IL1B), Matrix Metalloproteinase-9 (MMP9), C-C Motif Chemokine Ligand 2 (CCL2), RELA Proto-Oncogene (RELA), and CAMP Responsive Element Binding Protein 1 (CREB1) were identified as key targets of HDW in the treatment of PCa. The protein-protein interaction (PPI) cluster demonstrated that CREB1 was the seed in this cluster, indicating that CREB1 plays an important role in connecting other nodes in the PPI network. This enrichment demonstrated that HDW was highly related to translesion synthesis, unfolded protein binding, regulation of mitotic recombination, phosphatidylinositol and its kinase-mediated signaling, nucleotide excision repair, regulation of DNA recombination, and DNA topological change. The enrichment results also showed that the underlying mechanism of HDW against PCa may be due to its coordinated regulation of several cancer-related pathways, such as angiogenesis, cell differentiation, migration, apoptosis, invasion, and proliferation.
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Affiliation(s)
- Yanan Song
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China.
- Newborn Medicine, Boston Children's Hospital, Boston, MA 02115, USA.
| | - Haiyan Wang
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China.
| | - Yajing Pan
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China.
| | - Tonghua Liu
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China.
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Sánchez-Nieto B, Romero-Expósito M, Terrón J, Irazola L, García Hernández M, Mateos J, Roselló J, Planes D, Paiusco M, Sánchez-Doblado F. External photon radiation treatment for prostate cancer: Uncomplicated and cancer-free control probability assessment of 36 plans. Phys Med 2019; 66:88-96. [DOI: 10.1016/j.ejmp.2019.09.076] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2019] [Revised: 08/18/2019] [Accepted: 09/11/2019] [Indexed: 10/25/2022] Open
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Lee WR. Proton‐beam therapy after radical prostatectomy: Continued DVH idolatry? Cancer 2019; 125:4136-4138. [DOI: 10.1002/cncr.32456] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2019] [Revised: 07/11/2019] [Accepted: 07/16/2019] [Indexed: 01/22/2023]
Affiliation(s)
- W. Robert Lee
- Department of Radiation Oncology Duke University Durham North Carolina
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Forward- and Inverse-Planned Intensity-Modulated Radiotherapy in the CHHiP Trial: A Comparison of Dosimetry and Normal Tissue Toxicity. Clin Oncol (R Coll Radiol) 2019; 31:600-610. [PMID: 31178346 PMCID: PMC6688097 DOI: 10.1016/j.clon.2019.05.002] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2019] [Revised: 03/21/2019] [Accepted: 03/27/2019] [Indexed: 02/07/2023]
Abstract
AIMS The CHHiP (Conventional or Hypofractionated High-dose Intensity Modulated Radiotherapy In Prostate Cancer; CRUK/06/016) trial investigated hypofractionated radiotherapy for localised prostate cancer. Forward- (FP) or inverse-planned (IP) intensity-modulated techniques were permitted. Dose-volume histogram and toxicity data were compared to explore the effects of planning method. MATERIALS AND METHODS In total, 337 participants with intermediate-risk disease and prospectively collected toxicity data were included. Patients were matched on prostate and rectum/bladder volumes and on radiotherapy dose for toxicity comparisons. The primary outcome was grade 2 or higher Radiation Therapy Oncology Group (RTOG) bowel or bladder toxicity at 2 years. RESULTS IP patients had smaller volumes of rectum irradiated to 50-70 Gy (P < 0.001); FP patients had smaller volumes of bladder irradiated to 74 Gy (P = 0.001). Acute grade 2 + bowel toxicity was worse with FP (27/53 [52%]; 11/53 [21%] IP; P = 0.0002); with no significant differences in acute urinary toxicity. At 2 years, RTOG grade 2 + bowel toxicity rates were FP 0/53 and IP 2/53 and RTOG grade 2 + bladder rates were FP 0/54 and IP 1/57. CONCLUSIONS Significant differences were found between dose-volume histograms from FP and IP methods. IP may result in small reductions in acute bowel toxicity but both techniques were associated with low rates of late radiotherapy side-effects.
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Catton C, Lukka H. The evolution of fractionated prostate cancer radiotherapy. Lancet 2019; 394:361-362. [PMID: 31227371 DOI: 10.1016/s0140-6736(19)31338-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2019] [Accepted: 05/30/2019] [Indexed: 10/26/2022]
Affiliation(s)
- Charles Catton
- University of Toronto Department of Radiation Oncology, Princess Margaret Cancer Centre, Toronto, ON M5G 2M9, Canada.
| | - Himu Lukka
- McMaster University and Juravinski Cancer Centre, Hamilton, ON, Canada
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Lee SU, Cho KH, Park W, Cho WK, Kim JS, Wee CW, Kim YS, Kim JH, Nam TK, Cho J, Jeong SM, Kim Y, Shim SJ, Choi Y, Kim JS. Clinical Outcomes of Postoperative Radiotherapy Following Radical Prostatectomy in Patients with Localized Prostate Cancer: A Multicenter Retrospective Study (KROG 18-01) of a Korean Population. Cancer Res Treat 2019; 52:167-180. [PMID: 31291715 PMCID: PMC6962467 DOI: 10.4143/crt.2019.126] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2019] [Accepted: 06/21/2019] [Indexed: 11/21/2022] Open
Abstract
PURPOSE The purpose of this study was to investigate the clinical outcomes of postoperative radiotherapy (PORT) patients who underwent radical prostatectomy for localized prostate cancer. Materials and Methods Localized prostate cancer patients who received PORT after radical prostatectomy between 2001 and 2012 were identified retrospectively in a multi-institutional database. In total, 1,117 patients in 19 institutions were included. Biochemical failure after PORT was defined as prostate-specific antigen (PSA) ≥ nadir+2 after PORT or initiation of androgen deprivation therapy (ADT) for increasing PSA regardless of its value. RESULTS Ten-year biochemical failure-free survival, clinical failure-free survival, distant metastasisfree survival, overall survival (OS), and cause-specific survival were 60.5%, 76.2%, 84.4%, 91.1%, and 96.6%, respectively, at a median of 84 months after PORT. Pre-PORT PSA ≤ 0.5 ng/ml and Gleason's score ≤ 7 predicted favorable clinical outcomes, with 10-year OS rates of 92.5% and 94.1%, respectively. The 10-year OS rate was 82.7% for patients with a PSA > 1.0 ng/mL and 86.0% for patients with a Gleason score of 8-10. The addition of longterm ADT (≥ 12 months) to PORT improved OS, particularly in those with a Gleason score of 8-10 or ≥ T3b. CONCLUSION Clinical outcomes of PORT in a Korean prostate cancer population were very similar to those in Western countries. Lower Gleason score and serum PSA level at the time of PORT were significantly associated with favorable outcomes. Addition of long-term ADT (≥ 12 months) to PORT should be considered, particularly in unfavorable risk patients with Gleason scores of 8-10 or ≥ T3b.
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Affiliation(s)
- Sung Uk Lee
- The Proton Therapy Center, Research Institute and Hospital, National Cancer Center, Goyang, Korea
| | - Kwan Ho Cho
- The Proton Therapy Center, Research Institute and Hospital, National Cancer Center, Goyang, Korea
| | - Won Park
- Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Won Kyung Cho
- Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jae-Sung Kim
- Department of Radiation Oncology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Chan Woo Wee
- Department of Radiation Oncology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Young Seok Kim
- Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jin Ho Kim
- Department of Radiation Oncology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Taek-Keun Nam
- Department of Radiation Oncology, Chonnam National University Hwasun Hospital, Chonnam National University College of Medicine, Hwasun, Korea
| | - Jaeho Cho
- Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea
| | - Song Mi Jeong
- Department of Radiation Oncology, Ewha Womans University Medical Center, Ewha Womans University College of Medicine, Seoul, Korea
| | - Youngkyong Kim
- Department of Radiation Oncology, Kyung Hee University Hospital, Kyung Hee University College of Medicine, Seoul, Korea
| | - Su Jung Shim
- Department of Radiation Oncology, Eulji Hospital, Eulji University School of Medicine, Seoul, Korea
| | - Youngmin Choi
- Department of Radiation Oncology, Dong-A University Hospital, Dong-A University School of Medicine, Busan, Korea
| | - Jun-Sang Kim
- Department of Radiation Oncology, Chungnam National University College of Medicine, Daejeon, Korea
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Chauhan DS, Reddy BPK, Mishra SK, Prasad R, Dhanka M, Vats M, Ravichandran G, Poojari D, Mhatre O, De A, Srivastava R. Comprehensive Evaluation of Degradable and Cost-Effective Plasmonic Nanoshells for Localized Photothermolysis of Cancer Cells. LANGMUIR : THE ACS JOURNAL OF SURFACES AND COLLOIDS 2019; 35:7805-7815. [PMID: 31090425 DOI: 10.1021/acs.langmuir.8b03460] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/09/2023]
Abstract
Integrating the concept of biodegradation and light-triggered localized therapy in a functional nanoformulation is the current approach in onco-nanomedicine. Morphology control with an enhanced photothermal response, minimal toxicity, and X-ray attenuation of polymer-based nanoparticles is a critical concern for image-guided photothermal therapy. Herein, we describe the simple design of cost-effective and degradable polycaprolactone-based plasmonic nanoshells for the integrated photothermolysis as well as localized imaging of cancer cells. The gold-deposited polycaprolactone-based plasmonic nanoshells (AuPCL NS) are synthesized in a scalable and facile way under ambient conditions. The synthesized nanoshells are monodisperse, fairly stable, and highly inert even at five times (250 μg/mL) the therapeutic concentration in a week-long test. AuPCL NS are capable of delivering standalone photothermal therapy for the complete ablation of cancer cells without using any anticancerous drugs and causing toxicity. It delivers the same therapeutic efficacy to different cancer cell lines, irrespective of their chemorefractory status and also works as a potential computed tomography contrast agent for the integrated imaging-directed photothermal cancer therapy. High biocompatibility, degradability, and promising photothermal efficacy of AuPCL NS are attractive aspects of this report that could open new horizons of localized plasmonic photothermal therapy for healthcare applications.
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Affiliation(s)
- Deepak S Chauhan
- Department of Biosciences and Bioengineering (BSBE) , Indian Institute of Technology Bombay , Powai, Mumbai 400076 , India
| | - B Pradeep K Reddy
- Department of Biosciences and Bioengineering (BSBE) , Indian Institute of Technology Bombay , Powai, Mumbai 400076 , India
| | - Sumit K Mishra
- Molecular Functional Imaging Lab , Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre , Kharghar, Navi Mumbai 410210 , India
| | - Rajendra Prasad
- Department of Biosciences and Bioengineering (BSBE) , Indian Institute of Technology Bombay , Powai, Mumbai 400076 , India
| | - Mukesh Dhanka
- Department of Biosciences and Bioengineering (BSBE) , Indian Institute of Technology Bombay , Powai, Mumbai 400076 , India
| | - Mukti Vats
- Department of Biosciences and Bioengineering (BSBE) , Indian Institute of Technology Bombay , Powai, Mumbai 400076 , India
| | - Gayathri Ravichandran
- Molecular Functional Imaging Lab , Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre , Kharghar, Navi Mumbai 410210 , India
| | - Deeksha Poojari
- Department of Biosciences and Bioengineering (BSBE) , Indian Institute of Technology Bombay , Powai, Mumbai 400076 , India
| | - Omkar Mhatre
- Department of Biosciences and Bioengineering (BSBE) , Indian Institute of Technology Bombay , Powai, Mumbai 400076 , India
| | - Abhijit De
- Molecular Functional Imaging Lab , Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre , Kharghar, Navi Mumbai 410210 , India
| | - Rohit Srivastava
- Department of Biosciences and Bioengineering (BSBE) , Indian Institute of Technology Bombay , Powai, Mumbai 400076 , India
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Hatano K, Tohyama N, Kodama T, Okabe N, Sakai M, Konoeda K. Current status of intensity‐modulated radiation therapy for prostate cancer: History, clinical results and future directions. Int J Urol 2019; 26:775-784. [DOI: 10.1111/iju.14011] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2019] [Accepted: 04/07/2019] [Indexed: 01/05/2023]
Affiliation(s)
- Kazuo Hatano
- Division of Radiation Oncology Tokyo‐Bay Advanced Imaging & Radiation Oncology Clinic/Makuhari Chiba Japan
| | - Naoki Tohyama
- Division of Radiation Oncology Tokyo‐Bay Advanced Imaging & Radiation Oncology Clinic/Makuhari Chiba Japan
| | - Takashi Kodama
- Division of Radiation Oncology Tokyo‐Bay Advanced Imaging & Radiation Oncology Clinic/Makuhari Chiba Japan
| | - Naoyuki Okabe
- Division of Radiation Oncology Tokyo‐Bay Advanced Imaging & Radiation Oncology Clinic/Makuhari Chiba Japan
| | - Mitsuhiro Sakai
- Division of Radiation Oncology Tokyo‐Bay Advanced Imaging & Radiation Oncology Clinic/Makuhari Chiba Japan
| | - Koichi Konoeda
- Division of Radiation Oncology Tokyo‐Bay Advanced Imaging & Radiation Oncology Clinic/Makuhari Chiba Japan
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Proton versus photon-based radiation therapy for prostate cancer: emerging evidence and considerations in the era of value-based cancer care. Prostate Cancer Prostatic Dis 2019; 22:509-521. [PMID: 30967625 DOI: 10.1038/s41391-019-0140-7] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2018] [Revised: 01/30/2019] [Accepted: 02/25/2019] [Indexed: 12/30/2022]
Abstract
BACKGROUND Advances in radiation technology have transformed treatment options for patients with localized prostate cancer. The evolution of three-dimensional conformal radiation therapy and intensity-modulated radiation therapy (IMRT) have allowed physicians to spare surrounding normal organs and reduce adverse effects. The introduction of proton beam technology and its physical advantage of depositing its energy in tissue at the end-of-range maximum may potentially spare critical organs such as the bladder and rectum in prostate cancer patients. Data thus far are limited to large, observational studies that have not yet demonstrated a definite benefit of protons over conventional treatment with IMRT. The cost of proton beam treatment adds to the controversy within the field. METHODS We performed an extensive literature review for all proton treatment-related prostate cancer studies. We discuss the history of proton beam technology, as well as its role in the treatment of prostate cancer, associated controversies, novel technology trends, a discussion of cost-effectiveness, and an overview of the ongoing modern large prospective studies that aim to resolve the debate between protons and photons for prostate cancer. RESULTS Present data have demonstrated that proton beam therapy is safe and effective compared with the standard treatment options for prostate cancer. While dosimetric studies suggest lower whole-body radiation dose and a theoretically higher relative biological effectiveness in prostate cancer compared with photons, no studies have demonstrated a clear benefit with protons. CONCLUSIONS Evolving trends in proton treatment delivery and proton center business models are helping to reduce costs. Introduction of existing technology into proton delivery allows further control of organ motion and addressing organs-at-risk. Finally, the much-awaited contemporary studies comparing photon with proton-based treatments, with primary endpoints of patient-reported quality-of-life, will help us understand the differences between proton and photon-based treatments for prostate cancer in the modern era.
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Zhong QH, Liu ZZ, Yuan ZX, Ma TH, Huang XY, Wang HM, Chen DC, Wang JP, Wang L. Efficacy and complications of argon plasma coagulation for hemorrhagic chronic radiation proctitis. World J Gastroenterol 2019; 25:1618-1627. [PMID: 30983821 PMCID: PMC6452229 DOI: 10.3748/wjg.v25.i13.1618] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2019] [Revised: 02/20/2019] [Accepted: 02/23/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Chronic radiation proctitis (CRP) is a complication which occurs in 1%-5% of patients who undergo radiotherapy for pelvic malignancies. Although a wide range of therapeutic modalities are available, there is no literature to date showing any particularly appropriate therapeutic modality for each disease stage. Argon plasma coagulation (APC) is currently recommended as the first-choice treatment for hemorrhagic CRP, however, its indication based on long-term follow-up is still unclear. On the hypothesis that the long-term efficacy and safety of APC are not fully understood, we reviewed APC treatment for patients with hemorrhagic CRP from a single center.
AIM To assess the long-term efficacy and safety of APC for hemorrhagic CRP.
METHODS This is a retrospective study of consecutive patients treated with APC for hemorrhagic CRP from January 2013 to October 2017. Demographics, clinical variables, and typical endoscopic features were recorded independently. Success was defined as either cessation of bleeding or only occasional traces of bloody stools with no further treatments for at least 12 mo after the last APC treatment. We performed univariate and multivariate analyses to identify factors associated with success and risk factors for fistulas.
RESULTS Forty-five patients with a median follow-up period of 24 mo (range: 12-67 mo) were enrolled. Fifteen (33.3%) patients required blood transfusion before APC. Successful treatment with APC was achieved in 31 (68.9%) patients. The mean number of APC sessions was 1.3 (1-3). Multivariate analysis showed that APC failure was independently associated with telangiectasias present on more than 50% of the surface area [odds ratio (OR) = 6.53, 95% confidence interval (CI): 1.09-39.19, P = 0.04] and ulcerated area greater than 1 cm2 (OR = 8.15, 95%CI: 1.63-40.88, P = 0.01). Six (13.3%) patients had severe complications involving rectal fistulation. The only factor significantly associated with severe complications was ulcerated area greater than 1 cm2 (P = 0.035).
CONCLUSION The long-term efficacy of APC for hemorrhagic CRP is uncertain in patients with telangiectasias present on > 50% of the surface area and ulceration > 1 cm2.
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Affiliation(s)
- Qing-Hua Zhong
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Sun Yat-sen University, Guangzhou 510655, Guangdong Province, China
- Department of Colorectal Surgery, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, Guangdong Province, China
| | - Zhan-Zhen Liu
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Sun Yat-sen University, Guangzhou 510655, Guangdong Province, China
- Department of Colorectal Surgery, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, Guangdong Province, China
| | - Zi-Xu Yuan
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Sun Yat-sen University, Guangzhou 510655, Guangdong Province, China
- Department of Colorectal Surgery, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, Guangdong Province, China
| | - Teng-Hui Ma
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Sun Yat-sen University, Guangzhou 510655, Guangdong Province, China
- Department of Colorectal Surgery, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, Guangdong Province, China
| | - Xiao-Yan Huang
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Sun Yat-sen University, Guangzhou 510655, Guangdong Province, China
- Guangdong Institute of Gastroenterology, Guangzhou 510655, Guangdong Province, China
| | - Huai-Ming Wang
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Sun Yat-sen University, Guangzhou 510655, Guangdong Province, China
- Department of Colorectal Surgery, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, Guangdong Province, China
| | - Dai-Ci Chen
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Sun Yat-sen University, Guangzhou 510655, Guangdong Province, China
- Guangdong Institute of Gastroenterology, Guangzhou 510655, Guangdong Province, China
| | - Jian-Ping Wang
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Sun Yat-sen University, Guangzhou 510655, Guangdong Province, China
- Department of Colorectal Surgery, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, Guangdong Province, China
- Guangdong Institute of Gastroenterology, Guangzhou 510655, Guangdong Province, China
| | - Lei Wang
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Sun Yat-sen University, Guangzhou 510655, Guangdong Province, China
- Department of Colorectal Surgery, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, Guangdong Province, China
- Guangdong Institute of Gastroenterology, Guangzhou 510655, Guangdong Province, China
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Can proton therapy be considered a standard of care in oncology? Lessons from the United States. Br J Cancer 2019; 120:775-776. [PMID: 30911089 PMCID: PMC6474263 DOI: 10.1038/s41416-018-0324-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2018] [Revised: 10/03/2018] [Accepted: 10/04/2018] [Indexed: 11/10/2022] Open
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Evolution of definitive external beam radiation therapy in the treatment of prostate cancer. World J Urol 2019; 38:565-591. [PMID: 30850855 DOI: 10.1007/s00345-019-02661-6] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2018] [Accepted: 01/30/2019] [Indexed: 12/30/2022] Open
Abstract
PURPOSE Although the clinical significance of a diagnosis of prostate cancer for some men is debated, for many men it leads to significant morbidity and mortality. Radical treatment of clinically localized prostate cancer has been shown to improve survival in men with intermediate or high-risk disease. There is no high level evidence to support the superiority of radical prostatectomy, with or without adjuvant or salvage external beam radiotherapy in comparison to definitive radiotherapy with or without androgen deprivation, and the choice should be individualized. External beam radiation therapy practices are in constant evolution, and numerous strategies have been investigated to improve either efficacy or reduce toxicity, or both. METHODS Randomized controlled trials investigating strategies to improve efficacy, reduce toxicity, or both of external beam radiotherapy have been reviewed in men with prostate cancer without nodal or distant metastases. These strategies include the use of neo-adjuvant and adjuvant androgen deprivation, dose-escalation, hypofractionation, whole pelvic radiation therapy, incorporation of improved imaging, image- guided radiation therapy, and adjuvant systemic therapy. The evidence to date for these strategies is discussed, noting limitations in applying the results of reported trials to men treated in contemporary settings. RESULTS A number of strategies have shown improvements in biochemical control using external beam radiotherapy. To date, only with the use of androgen deprivation therapy has this translated into improvements in disease specific and overall survival. This may reflect the long natural history of prostate cancer and high incidence of competing risks. Technological advances have enabled dose escalation with reduced toxicity, of paramount importance given the long natural history. RESULTS The use of external beam radiation therapy in prostate cancer is evolving with numerous strategies incorporated to improve outcomes. The optimum dose and fractionation and use of androgen deprivation or systemic adjuvants for each man is unclear based on current evidence and prognostic and predictive parameters. Patient preferences play an important role in chosen therapy. It is hoped that future studies better capture all prostate cancer- and treatment- related morbidity to clarify the optimal therapy choices for each man with prostate cancer.
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50
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Morgan SC, Rumble RB, Sandler H. Hypofractionated Radiation Therapy for Localized Prostate Cancer: An ASTRO, ASCO, and AUA Evidence-Based Guideline Summary. J Oncol Pract 2019. [DOI: 10.1200/jop.18.00616] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Affiliation(s)
- Scott C. Morgan
- The Ottawa Hospital and University of Ottawa, Ottawa, Ontario, Canada
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