|
1
|
Vischioni B, Barcellini A, Magro G, Rotondi M, Durante M, Facoetti A, Thariat J, Orlandi E. Radioresistant, Rare, Recurrent, and Radioinduced: 4 Rs of Hadrontherapy for Patients Selections. Int J Part Ther 2025; 15:100737. [PMID: 39927286 PMCID: PMC11804719 DOI: 10.1016/j.ijpt.2024.100737] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2024] [Revised: 12/22/2024] [Accepted: 12/23/2024] [Indexed: 02/11/2025] Open
Abstract
Purpose To describe the role of hadrontherapy (HT) in treating radioresistant, rare, recurrent, and radio-induced tumors, which can be defined, in assonance with the 4Rs of radiobiology, the "4Rs" of HT indications. Materials and Methods This is a narrative review written by a multidisciplinary team consisting of radiation oncologists, radiobiologists, and physicists on the current literature on HT, particularly carbon ion radiation therapy. To refine HT indications within the context of the "4Rs" framework, we evaluated tumor histologies across different clinical indication settings and emphasized the radiobiological mechanisms contributing to the effectiveness of HT. Results For rare, radioresistant, recurrent, and radio-induced tumors, HT has proven to be effective and safe, achieving high rates of local response with mild toxicity. The current review shows that the biological parameters can assist clinicians in identifying appropriate cases for HT treatment. Conclusion Biological characteristics of the tumor support the administration of HT in radioresistant, rare, recurrent, and radio-induced tumors and should be considered during multidisciplinary discussions.
Collapse
Affiliation(s)
- Barbara Vischioni
- Radiation Oncology Unit, Clinical Department, CNAO National Center for Oncological Hadrontherapy, Pavia, Italy
| | - Amelia Barcellini
- Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy
- Radiation Oncology Unit, Clinical Department, CNAO National Center for Oncological Hadrontherapy, Pavia, Italy
| | - Giuseppe Magro
- Medical Physics Unit, Clinical Department, CNAO National Center for Oncological Hadrontherapy, Pavia, Italy
| | - Marco Rotondi
- Radiation Oncology Unit, Clinical Department, CNAO National Center for Oncological Hadrontherapy, Pavia, Italy
| | - Marco Durante
- GSI Helmholtzzentrum für Schwerionenforschung, Biophysics Department, Darmstadt, Germany
- Department of Physics, Institute of Condensed Matter Physics, Technische Universität Darmstadt, Darmstadt, Germany
- Department of Physics "Ettore Pancini," University Federico II, Naples
| | - Angelica Facoetti
- Radiobiology Unit, Research and Development Department, CNAO National Center for Oncological Hadrontherapy, Pavia, Italy
| | - Juliette Thariat
- Département de Radiothérapie, Centre François Baclesse, Caen, France
| | - Ester Orlandi
- Department of Clinical, Surgical, Diagnostic, and Pediatric Sciences, University of Pavia, Pavia, Italy
- Radiation Oncology Unit, Clinical Department, CNAO National Center for Oncological Hadrontherapy, Pavia, Italy
| |
Collapse
|
|
2
|
Malouff TD, Newpower M, Bush A, Seneviratne D, Ebner DK. A Practical Primer on Particle Therapy. Pract Radiat Oncol 2024; 14:590-602. [PMID: 38844118 DOI: 10.1016/j.prro.2024.05.005] [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: 02/16/2024] [Revised: 05/15/2024] [Accepted: 05/21/2024] [Indexed: 06/22/2024]
Abstract
PURPOSE Particle therapy is a promising treatment technique that is becoming more commonly used. Although proton beam therapy remains the most commonly used particle therapy, multiple other heavier ions have been used in the preclinical and clinical settings, each with its own unique properties. This practical review aims to summarize the differences between the studied particles, discussing their radiobiological and physical properties with additional review of the available clinical data. METHODS AND MATERIALS A search was carried out on the PubMed databases with search terms related to each particle. Relevant radiobiology, physics, and clinical studies were included. The articles were summarized to provide a practical resource for practicing clinicians. RESULTS A total of 113 articles and texts were included in our narrative review. Currently, proton beam therapy has the most data and is the most widely used, followed by carbon, helium, and neutrons. Although oxygen, neon, silicon, and argon have been used clinically, their future use will likely remain limited as monotherapy. CONCLUSIONS This review summarizes the properties of each of the clinically relevant particles. Protons, helium, and carbon will likely remain the most commonly used, although multi-ion therapy is an emerging technique.
Collapse
Affiliation(s)
- Timothy D Malouff
- Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota.
| | - Mark Newpower
- Department of Radiation Oncology, University of Oklahoma, OU Health Stephenson Cancer Center, Oklahoma City, Oklahoma
| | - Aaron Bush
- Department of Radiation Oncology, Mayo Clinic, Jacksonville, Florida
| | - Danushka Seneviratne
- Department of Radiation Oncology, University of Oklahoma, OU Health Stephenson Cancer Center, Oklahoma City, Oklahoma
| | - Daniel K Ebner
- Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota
| |
Collapse
|
|
3
|
Zhang H, Zhu W, Pan W, Wan X, Li N, Tang B. Recent advances in spatio-temporally controllable systems for management of glioma. Asian J Pharm Sci 2024; 19:100954. [PMID: 39483717 PMCID: PMC11525460 DOI: 10.1016/j.ajps.2024.100954] [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: 02/07/2024] [Revised: 05/29/2024] [Accepted: 06/17/2024] [Indexed: 11/03/2024] Open
Abstract
Malignant glioma remains one of the most aggressive intracranial tumors with devastating clinical outcomes despite the great advances in conventional treatment approaches, including surgery and chemotherapy. Spatio-temporally controllable approaches to glioma are now being actively investigated due to the preponderance, including spatio-temporal adjustability, minimally invasive, repetitive properties, etc. External stimuli can be readily controlled by adjusting the site and density of stimuli to exert the cytotoxic on glioma tissue and avoid undesired injury to normal tissues. It is worth noting that the removability of external stimuli allows for on-demand treatment, which effectively reduces the occurrence of side effects. In this review, we highlight recent advancements in drug delivery systems for spatio-temporally controllable treatments of glioma, focusing on the mechanisms and design principles of sensitizers utilized in these controllable therapies. Moreover, the potential challenges regarding spatio-temporally controllable therapy for glioma are also described, aiming to provide insights into future advancements in this field and their potential clinical applications.
Collapse
Affiliation(s)
- Huiwen Zhang
- College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Institute of Molecular and Nano Science, Shandong Normal University, Jinan 250014, China
| | - Wanqi Zhu
- College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Institute of Molecular and Nano Science, Shandong Normal University, Jinan 250014, China
| | - Wei Pan
- College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Institute of Molecular and Nano Science, Shandong Normal University, Jinan 250014, China
| | - Xiuyan Wan
- College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Institute of Molecular and Nano Science, Shandong Normal University, Jinan 250014, China
| | - Na Li
- College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Institute of Molecular and Nano Science, Shandong Normal University, Jinan 250014, China
| | - Bo Tang
- College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Institute of Molecular and Nano Science, Shandong Normal University, Jinan 250014, China
- Laoshan Laboratory, Qingdao 266237, China
| |
Collapse
|
|
4
|
Valerius AR, Webb LM, Thomsen A, Lehrer EJ, Breen WG, Campian JL, Riviere-Cazaux C, Burns TC, Sener U. Review of Novel Surgical, Radiation, and Systemic Therapies and Clinical Trials in Glioblastoma. Int J Mol Sci 2024; 25:10570. [PMID: 39408897 PMCID: PMC11477105 DOI: 10.3390/ijms251910570] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2024] [Revised: 09/25/2024] [Accepted: 09/26/2024] [Indexed: 10/20/2024] Open
Abstract
Glioblastoma (GBM) is the most common malignant primary brain tumor in adults. Despite an established standard of care including surgical resection, radiation therapy, and chemotherapy, GBM unfortunately is associated with a dismal prognosis. Therefore, researchers are extensively evaluating avenues to expand GBM therapy and improve outcomes in patients with GBM. In this review, we provide a broad overview of novel GBM therapies that have recently completed or are actively undergoing study in clinical trials. These therapies expand across medical, surgical, and radiation clinical trials. We additionally review methods for improving clinical trial design in GBM.
Collapse
Affiliation(s)
| | - Lauren M. Webb
- Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA (U.S.)
| | - Anna Thomsen
- Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA (U.S.)
| | - Eric J. Lehrer
- Department of Radiation Oncology, Mayo Clinic, Rochester, MN 55905, USA
| | - William G. Breen
- Department of Radiation Oncology, Mayo Clinic, Rochester, MN 55905, USA
| | - Jian L. Campian
- Department of Medical Oncology, Mayo Clinic, Rochester, MN 55905, USA
| | | | - Terry C. Burns
- Department of Neurosurgery, Mayo Clinic, Rochester, MN 55905, USA
| | - Ugur Sener
- Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA (U.S.)
- Department of Medical Oncology, Mayo Clinic, Rochester, MN 55905, USA
| |
Collapse
|
|
5
|
Lv Y, Wang C, Liu R, Wu S, Chen J, Zheng X, Jiang T, Chen L. NUP37 promotes the proliferation and invasion of glioma cells through DNMT1-mediated methylation. Cell Death Discov 2024; 10:373. [PMID: 39174498 PMCID: PMC11341718 DOI: 10.1038/s41420-024-02138-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2024] [Revised: 07/30/2024] [Accepted: 08/07/2024] [Indexed: 08/24/2024] Open
Abstract
Nuclear regulation has potential in cancer therapy, with the nuclear pore complex (NPC) serving as a critical channel between the nucleus and cytoplasm, playing a role in regulating various biological processes and cancer. DNA methylation, an epigenetic modification mediated by DNA methyltransferases (DNMTs), influences gene expression and cell differentiation, and is crucial for the development and progression of tumor cells. Gliomas are the most common primary brain tumors, with glioblastoma being particularly aggressive, characterized by invasiveness, migration capability, and resistance to conventional treatments, resulting in poor prognosis. Our study revealed that the expression level of NUP37 affects the proliferation and invasion of glioma cells, and that the overexpression of DNMT1 can alleviate the adverse effects caused by NUP37 depletion. These findings suggest that NUP37 promotes the proliferation and invasion of glioma cells through its interaction with DNMT1.
Collapse
Affiliation(s)
- Yongqiang Lv
- Department of Neurosurgery, The Third Affiliated Hospital of Suzhou University, Changzhou, Jiangsu, China
- Department of Tumor Biological Treatment, The Third Affiliated Hospital of Suzhou University, Changzhou, Jiangsu, China
| | - Chaolian Wang
- Department of Neurosurgery, The Third Affiliated Hospital of Suzhou University, Changzhou, Jiangsu, China
- Department of Tumor Biological Treatment, The Third Affiliated Hospital of Suzhou University, Changzhou, Jiangsu, China
| | - Ruoyu Liu
- Department of Neurosurgery, The Third Affiliated Hospital of Suzhou University, Changzhou, Jiangsu, China
- Department of Tumor Biological Treatment, The Third Affiliated Hospital of Suzhou University, Changzhou, Jiangsu, China
| | - Shaoxian Wu
- Department of Tumor Biological Treatment, The Third Affiliated Hospital of Suzhou University, Changzhou, Jiangsu, China
- Jiangsu Engineering Research Center for Tumor Immunotherapy, The Third Affiliated Hospital of Suzhou University, Changzhou, Jiangsu, China
- Institute of Cell Therapy, The Third Affiliated Hospital of Suzhou University, Changzhou, Jiangsu, China
| | - Junjun Chen
- Department of Tumor Biological Treatment, The Third Affiliated Hospital of Suzhou University, Changzhou, Jiangsu, China
- Jiangsu Engineering Research Center for Tumor Immunotherapy, The Third Affiliated Hospital of Suzhou University, Changzhou, Jiangsu, China
- Institute of Cell Therapy, The Third Affiliated Hospital of Suzhou University, Changzhou, Jiangsu, China
| | - Xiao Zheng
- Department of Tumor Biological Treatment, The Third Affiliated Hospital of Suzhou University, Changzhou, Jiangsu, China
- Jiangsu Engineering Research Center for Tumor Immunotherapy, The Third Affiliated Hospital of Suzhou University, Changzhou, Jiangsu, China
- Institute of Cell Therapy, The Third Affiliated Hospital of Suzhou University, Changzhou, Jiangsu, China
| | - Tianwei Jiang
- Department of Neurosurgery, The Third Affiliated Hospital of Suzhou University, Changzhou, Jiangsu, China.
- Department of Tumor Biological Treatment, The Third Affiliated Hospital of Suzhou University, Changzhou, Jiangsu, China.
| | - Lujun Chen
- Department of Tumor Biological Treatment, The Third Affiliated Hospital of Suzhou University, Changzhou, Jiangsu, China.
- Jiangsu Engineering Research Center for Tumor Immunotherapy, The Third Affiliated Hospital of Suzhou University, Changzhou, Jiangsu, China.
- Institute of Cell Therapy, The Third Affiliated Hospital of Suzhou University, Changzhou, Jiangsu, China.
| |
Collapse
|
|
6
|
Li X, Zhang Y, Ye Y, Tian S, Hu T, Chai H, Zhang T, Wen F. Carbon-ion radiotherapy alone vs. standard dose photon radiation with carbon-ion radiotherapy boost for high-grade gliomas: a retrospective study. BMC Cancer 2024; 24:837. [PMID: 39003464 PMCID: PMC11245814 DOI: 10.1186/s12885-024-12606-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2024] [Accepted: 07/05/2024] [Indexed: 07/15/2024] Open
Abstract
BACKGROUND This study aimed to compare the survival outcome and side effects in patients with primary high-grade glioma (HGG) who received carbon ion radiotherapy (CIRT) alone or as a boost strategy after photon radiation (photon + CIRTboost). PATIENTS AND METHODS Thirty-four (34) patients with histologically confirmed HGG and received CIRT alone or Photon + CIRTboost, with concurrent temozolomide between 2020.03-2023.08 in Wuwei Cancer Hospital & Institute, China were retrospectively reviewed. Overall survival (OS), progression-free survival (PFS), and acute and late toxicities were analyzed and compared. RESULTS Eight WHO grade 3 and 26 grade 4 patients were included in the analysis. The median PFS in the CIRT alone and Photon + CIRTboost groups were 15 and 19 months respectively for all HGG cases, and 15 and 17.5 months respectively for grade 4 cases. The median OS in the CIRT alone and Photon + CIRTboost groups were 28 and 31 months respectively for all HGG cases, and 21 and 19 months respectively for grade 4 cases. No significant difference in these survival outcomes was observed between the CIRT alone and Photon + CIRTboost groups. Only grade 1 acute toxicities were observed in CIRT alone and Photon + CIRTboost groups. CIRT alone group had a significantly lower ratio of acute toxicities compared to Photon + CIRTboost (3/18 vs. 9/16, p = 0.03). No significant difference in late toxicities was observed. CONCLUSION Both CIRT alone and Photon + CIRTboost with concurrent temozolomide are safe, without significant differences in PFS and OS in HGG patients. It is meaningful to explore whether dose escalation of CIRTboost might improve survival outcomes of HGG patients in future randomized trials.
Collapse
Affiliation(s)
- XiaoJun Li
- Heavy Ion Radiotherapy Department, Wuwei Cancer Hospital & Institute, Wuwei Academy of Medical Sciences, No. 31 Sanitary Lane, Haizang Road, Wuwei, 733000, Gansu Province, China
| | - YanShan Zhang
- Heavy Ion Radiotherapy Department, Wuwei Cancer Hospital & Institute, Wuwei Academy of Medical Sciences, No. 31 Sanitary Lane, Haizang Road, Wuwei, 733000, Gansu Province, China
| | - YanCheng Ye
- Heavy Ion Radiotherapy Department, Wuwei Cancer Hospital & Institute, Wuwei Academy of Medical Sciences, No. 31 Sanitary Lane, Haizang Road, Wuwei, 733000, Gansu Province, China.
| | - SuQing Tian
- Department of Radiation Oncology, Peking University Third Hospital, Beijing, 100191, China
| | - TingChao Hu
- Heavy Ion Radiotherapy Department, Wuwei Cancer Hospital & Institute, Wuwei Academy of Medical Sciences, No. 31 Sanitary Lane, Haizang Road, Wuwei, 733000, Gansu Province, China
| | - HongYu Chai
- Heavy Ion Radiotherapy Department, Wuwei Cancer Hospital & Institute, Wuwei Academy of Medical Sciences, No. 31 Sanitary Lane, Haizang Road, Wuwei, 733000, Gansu Province, China
| | - TianE Zhang
- Heavy Ion Radiotherapy Department, Wuwei Cancer Hospital & Institute, Wuwei Academy of Medical Sciences, No. 31 Sanitary Lane, Haizang Road, Wuwei, 733000, Gansu Province, China
| | - Faxin Wen
- Heavy Ion Radiotherapy Department, Wuwei Cancer Hospital & Institute, Wuwei Academy of Medical Sciences, No. 31 Sanitary Lane, Haizang Road, Wuwei, 733000, Gansu Province, China
| |
Collapse
|
|
7
|
Valerius AR, Webb LM, Sener U. Novel Clinical Trials and Approaches in the Management of Glioblastoma. Curr Oncol Rep 2024; 26:439-465. [PMID: 38546941 DOI: 10.1007/s11912-024-01519-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/14/2024] [Indexed: 05/02/2024]
Abstract
PURPOSE OF REVIEW The purpose of this review is to discuss a wide variety of novel therapies recently studied or actively undergoing study in patients with glioblastoma. This review also discusses current and future strategies for improving clinical trial design in patients with glioblastoma to maximize efficacy in discovering effective treatments. RECENT FINDINGS Over the years, there has been significant expansion in therapy modalities studied in patients with glioblastoma. These therapies include, but are not limited to, targeted molecular therapies, DNA repair pathway targeted therapies, immunotherapies, vaccine therapies, and surgically targeted radiotherapies. Glioblastoma is the most common malignant primary brain tumor in adults and unfortunately remains with poor overall survival following the current standard of care. Given the dismal prognosis, significant clinical and research efforts are ongoing with the goal of improving patient outcomes and enhancing quality and quantity of life utilizing a wide variety of novel therapies.
Collapse
Affiliation(s)
| | - Lauren M Webb
- Department of Neurology, Mayo Clinic, Rochester, MN, USA
| | - Ugur Sener
- Department of Neurology, Mayo Clinic, Rochester, MN, USA
- Department of Oncology, Mayo Clinic, Rochester, MN, USA
| |
Collapse
|
|
8
|
Mohamed AA, Alshaibi R, Faragalla S, Mohamed Y, Lucke-Wold B. Updates on management of gliomas in the molecular age. World J Clin Oncol 2024; 15:178-194. [PMID: 38455131 PMCID: PMC10915945 DOI: 10.5306/wjco.v15.i2.178] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2023] [Revised: 01/06/2024] [Accepted: 01/25/2024] [Indexed: 02/20/2024] Open
Abstract
Gliomas are primary brain tumors derived from glial cells of the central nervous system, afflicting both adults and children with distinct characteristics and therapeutic challenges. Recent developments have ushered in novel clinical and molecular prognostic factors, reshaping treatment paradigms based on classification and grading, determined by histological attributes and cellular lineage. This review article delves into the diverse treatment modalities tailored to the specific grades and molecular classifications of gliomas that are currently being discussed and used clinically in the year 2023. For adults, the therapeutic triad typically consists of surgical resection, chemotherapy, and radiotherapy. In contrast, pediatric gliomas, due to their diversity, require a more tailored approach. Although complete tumor excision can be curative based on the location and grade of the glioma, certain non-resectable cases demand a chemotherapy approach usually involving, vincristine and carboplatin. Additionally, if surgery or chemotherapy strategies are unsuccessful, Vinblastine can be used. Despite recent advancements in treatment methodologies, there remains a need of exploration in the literature, particularly concerning the efficacy of treatment regimens for isocitrate dehydrogenase type mutant astrocytomas and fine-tuned therapeutic approaches tailored for pediatric cohorts. This review article explores into the therapeutic modalities employed for both adult and pediatric gliomas in the context of their molecular classification.
Collapse
Affiliation(s)
- Ali Ahmed Mohamed
- Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, FL 33431, United States
| | - Rakan Alshaibi
- Herbert Wertheim College of Medicine, Florida International University, Miami, FL 33199, United States
| | - Steven Faragalla
- Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, FL 33431, United States
| | - Youssef Mohamed
- College of Osteopathic Medicine, Kansas City University, Joplin, MO 64804, United States
| | - Brandon Lucke-Wold
- Department of Neurosurgery, University of Florida, Gainesville, FL 32611, United States
| |
Collapse
|
|
9
|
Sokol O, Durante M. Carbon Ions for Hypoxic Tumors: Are We Making the Most of Them? Cancers (Basel) 2023; 15:4494. [PMID: 37760464 PMCID: PMC10526811 DOI: 10.3390/cancers15184494] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2023] [Revised: 09/07/2023] [Accepted: 09/07/2023] [Indexed: 09/29/2023] Open
Abstract
Hypoxia, which is associated with abnormal vessel growth, is a characteristic feature of many solid tumors that increases their metastatic potential and resistance to radiotherapy. Carbon-ion radiation therapy, either alone or in combination with other treatments, is one of the most promising treatments for hypoxic tumors because the oxygen enhancement ratio decreases with increasing particle LET. Nevertheless, current clinical practice does not yet fully benefit from the use of carbon ions to tackle hypoxia. Here, we provide an overview of the existing experimental and clinical evidence supporting the efficacy of C-ion radiotherapy in overcoming hypoxia-induced radioresistance, followed by a discussion of the strategies proposed to enhance it, including different approaches to maximize LET in the tumors.
Collapse
Affiliation(s)
- Olga Sokol
- Biophysics Department, GSI Helmholtzzentrum für Schwerionenforchung, Planckstraße 1, 64291 Darmstadt, Germany;
| | - Marco Durante
- Biophysics Department, GSI Helmholtzzentrum für Schwerionenforchung, Planckstraße 1, 64291 Darmstadt, Germany;
- Institute for Condensed Matter Physics, Technische Universität Darmstadt, Hochschulstraße 8, 64289 Darmstadt, Germany
| |
Collapse
|
|
10
|
Ebner D, Koto M, Furuichi W, Mori S. Simulation study of comparative dosimetric analysis of coplanar horizontal-port scanned carbon-ion beam therapy in the head and neck. Br J Radiol 2023; 96:20221138. [PMID: 37427708 PMCID: PMC10461273 DOI: 10.1259/bjr.20221138] [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: 12/02/2022] [Revised: 06/01/2023] [Accepted: 06/01/2023] [Indexed: 07/11/2023] Open
Abstract
OBJECTIVE Carbon-ion radiotherapy (CIRT) has demonstrated success in treating radioresistant disease within the head and neck, owing to its unique physical and radiobiological properties. Construction cost remains prohibitive; a center offering only a horizontal port may bridge this difficulty, but removal of the vertical port may prohibit treatment of disease near critical organs-at-risk. Building a center only containing a horizontal treatment port has been proposed as one method for cost savings. METHODS 20 complex cases of head and neck cancer previously treated with conventional CIRT were retrospectively planned using horizontal-port-only treatment incorporating non-coplanar treatment angles to achieve greater degrees of freedom. These were dosimetrically compared with the previous plans. RESULTS Comparable D95 coverage of both planning target volume and gross tumor volume with ability to meet organ-at-risk constraints were feasible with horizontal-port-only treatment. Collectively differences were noted in PTV D95, brain stem Dmax, contralateral eye Dmax and V10 Gy (RBE); further qualitative differences were noted on a plan-by-plan basis dependent on disease location. CONCLUSION Horizontal-port-only treatment employing non-coplanar angles was feasible for complicated head and neck disease typically treated with CIRT, though careful consideration is necessary on a plan-by-plan basis. ADVANCES IN KNOWLEDGE It is worth noting that non-coplanar approaches are not typically used with the current treatment gantry and may extend further the difference between horizontal port planning and a gantry-based gold-standard.
Collapse
Affiliation(s)
| | - Masashi Koto
- QST Hospital, National Institutes for Quantum Science and Technology, Chiba, Japan
| | - Wataru Furuichi
- Accelerator Engineering Corporation, Konakadai, Inage-Ku, Chiba, Japan
| | - Shinichiro Mori
- Institute for Quantum Medical Science, Quantum Life and Medical Science Directorate, National Institutes for Quantum Science and Technology, Chiba, Japan
| |
Collapse
|
|
11
|
Huang F, Li S, Wang X, Wang C, Pan X, Chen X, Zhang W, Hong J. Serum lipids concentration on prognosis of high-grade glioma. Cancer Causes Control 2023:10.1007/s10552-023-01710-1. [PMID: 37258987 DOI: 10.1007/s10552-023-01710-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2022] [Accepted: 05/03/2023] [Indexed: 06/02/2023]
Abstract
OBJECTIVE To investigate the effect of serum lipids concentration on the prognosis of high-grade glioma patients undergoing postoperative radiotherapy. METHODS Retrospective analysis of the patients with high-grade glioma who received postoperative Intensity Modulated Radiotherapy between 13 May 2013 and 12 September 2018 was performed. The patients were grouped according to the average values of serum total cholesterol, LDL, and HDL concentration in peripheral blood (before surgery, 6 months after therapy). Cox proportional hazards model was performed to determine whether the total cholesterol concentration, LDL concentration, and HDL concentration in peripheral blood before therapy and their changes after therapy were factors influencing the prognosis. RESULTS The results of COX regression analysis showed that the independent prognostic factors of high-grade glioma patients were pathological grade, the extent of resection, serum cholesterol concentration pre-surgery, and the change of LDL concentration from pre-surgery to post-therapy. The prognosis of patients with high serum total cholesterol concentration before therapy was worse than those of patients with low total cholesterol concentration. The 5-year survival rate and the median survival time of patients with high serum total cholesterol concentration before therapy were 4.9% and 23.6 months, but the low cholesterol concentration group were 19.6% and 24.5 months, respectively. Besides, the average serum LDL concentration in high-grade glioma patients gradually increased after therapy. The 5-year survival rate of patients and the median survival time with elevated LDL concentration after therapy is 11.8% and 20.4 months, but the reduced LDL concentration group was 16.7% and 28.4 months, respectively. The total cholesterol and LDL concentration increased significantly after therapy in Grade IV patients while Grade III patients did not. CONCLUSIONS The cholesterol concentration before therapy and LDL concentration change from pre-surgery to post-therapy are the factors that affect the prognosis of high-grade glioma patients who have undergone postoperative radiotherapy. In the final analysis, the high serum cholesterol pre-surgery and the increased in serum LDL concentration from pre-surgery to post-therapy were associated with worse survival of patients.
Collapse
Affiliation(s)
- Fei Huang
- Central Lab, First Affiliated Hospital, Fujian Medical University, No. 20 Chazhong Road, Taijiang District, Fuzhou, 350005, Fujian, China
- Central Laboratory, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350212, Fujian, China
- Key Laboratory of Radiation Biology of Fujian Higher Education Institutions, The First Affliated Hospital, Fujian Medical University, No.20 Chazhong Road, Taijiang District, Fuzhou, 350005, Fujian, China
- Fujian Provincial Key Laboratory of Precision Medicine for Cancer (Fujian Medical University), No. 20 Chazhong Road, Taijiang District, Fuzhou, 350005, Fujian, China
| | - Shan Li
- Department of Radiotherapy, Cancer Center, The First Affiliated Hospital of Fujian Medical University, No. 20 Chazhong Road, Taijiang District, Fuzhou, 350005, Fujian, China
- Key Laboratory of Radiation Biology of Fujian Higher Education Institutions, The First Affliated Hospital, Fujian Medical University, No.20 Chazhong Road, Taijiang District, Fuzhou, 350005, Fujian, China
- Fujian Provincial Key Laboratory of Precision Medicine for Cancer (Fujian Medical University), No. 20 Chazhong Road, Taijiang District, Fuzhou, 350005, Fujian, China
| | - Xuezhen Wang
- Department of Radiotherapy, Cancer Center, The First Affiliated Hospital of Fujian Medical University, No. 20 Chazhong Road, Taijiang District, Fuzhou, 350005, Fujian, China
| | - Caihong Wang
- Department of Radiotherapy, Cancer Center, The First Affiliated Hospital of Fujian Medical University, No. 20 Chazhong Road, Taijiang District, Fuzhou, 350005, Fujian, China
| | - Xiaoxian Pan
- Department of Radiotherapy, Cancer Center, The First Affiliated Hospital of Fujian Medical University, No. 20 Chazhong Road, Taijiang District, Fuzhou, 350005, Fujian, China
| | - Xiuying Chen
- Department of Radiotherapy, Cancer Center, The First Affiliated Hospital of Fujian Medical University, No. 20 Chazhong Road, Taijiang District, Fuzhou, 350005, Fujian, China
- Key Laboratory of Radiation Biology of Fujian Higher Education Institutions, The First Affliated Hospital, Fujian Medical University, No.20 Chazhong Road, Taijiang District, Fuzhou, 350005, Fujian, China
- Fujian Provincial Key Laboratory of Precision Medicine for Cancer (Fujian Medical University), No. 20 Chazhong Road, Taijiang District, Fuzhou, 350005, Fujian, China
| | - Weijian Zhang
- Department of Radiotherapy, Cancer Center, The First Affiliated Hospital of Fujian Medical University, No. 20 Chazhong Road, Taijiang District, Fuzhou, 350005, Fujian, China
- Key Laboratory of Radiation Biology of Fujian Higher Education Institutions, The First Affliated Hospital, Fujian Medical University, No.20 Chazhong Road, Taijiang District, Fuzhou, 350005, Fujian, China
- Fujian Provincial Key Laboratory of Precision Medicine for Cancer (Fujian Medical University), No. 20 Chazhong Road, Taijiang District, Fuzhou, 350005, Fujian, China
| | - Jinsheng Hong
- Department of Radiotherapy, Cancer Center, The First Affiliated Hospital of Fujian Medical University, No. 20 Chazhong Road, Taijiang District, Fuzhou, 350005, Fujian, China.
- Key Laboratory of Radiation Biology of Fujian Higher Education Institutions, The First Affliated Hospital, Fujian Medical University, No.20 Chazhong Road, Taijiang District, Fuzhou, 350005, Fujian, China.
- Fujian Provincial Key Laboratory of Precision Medicine for Cancer (Fujian Medical University), No. 20 Chazhong Road, Taijiang District, Fuzhou, 350005, Fujian, China.
| |
Collapse
|
|
12
|
Tejada Solís S, González Sánchez J, Iglesias Lozano I, Plans Ahicart G, Pérez Núñez A, Meana Carballo L, Gil Salú JL, Fernández Coello A, García Romero JC, Rodríguez de Lope Llorca A, García Duque S, Díez Valle R, Narros Giménez JL, Prat Acín R. Low grade gliomas guide-lines elaborated by the tumor section of Spanish Society of Neurosurgery. NEUROCIRUGIA (ENGLISH EDITION) 2023; 34:139-152. [PMID: 36446721 DOI: 10.1016/j.neucie.2022.11.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/09/2022] [Revised: 05/20/2022] [Accepted: 08/01/2022] [Indexed: 05/06/2023]
Abstract
Adult low-grade gliomas (Low Grade Gliomas, LGG) are tumors that originate from the glial cells of the brain and whose management involves great controversy, starting from the diagnosis, to the treatment and subsequent follow-up. For this reason, the Tumor Group of the Spanish Society of Neurosurgery (GT-SENEC) has held a consensus meeting, in which the most relevant neurosurgical issues have been discussed, reaching recommendations based on the best scientific evidence. In order to obtain the maximum benefit from these treatments, an individualised assessment of each patient should be made by a multidisciplinary team. Experts in each LGG treatment field have briefly described it based in their experience and the reviewed of the literature. Each area has been summarized and focused on the best published evidence. LGG have been surrounded by treatment controversy, although during the last years more accurate data has been published in order to reach treatment consensus. Neurosurgeons must know treatment options, indications and risks to participate actively in the decision making and to offer the best surgical treatment in every case.
Collapse
Affiliation(s)
- Sonia Tejada Solís
- Departamento de Neurocirugía, Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain; Departamento de Neurocirugía, Hospital Universitario HM Montepríncipe, Madrid, Spain.
| | - Josep González Sánchez
- Departamento de Neurocirugía, Hospital Clínic i Provincial de Barcelona, Barcelona, Spain; Departamento de Neurocirugía, Hospital Universitario HM Montepríncipe, Madrid, Spain
| | - Irene Iglesias Lozano
- Departamento de Neurocirugía, Hospital Universitario Puerta del Mar, Cádiz, Spain; Departamento de Neurocirugía, Hospital Universitario HM Montepríncipe, Madrid, Spain
| | - Gerard Plans Ahicart
- Departamento de Neurocirugía, Hospital Universitari Bellvitge, Barcelona, Spain; Departamento de Neurocirugía, Hospital Universitario HM Montepríncipe, Madrid, Spain
| | - Angel Pérez Núñez
- Departamento de Neurocirugía, Hospital Universitario 12 de Octubre, Madrid, Spain; Departamento de Neurocirugía, Hospital Universitario HM Montepríncipe, Madrid, Spain
| | - Leonor Meana Carballo
- Departamento de Neurocirugía, Centro Médico de Asturias, Oviedo, Spain; Departamento de Neurocirugía, Hospital Universitario HM Montepríncipe, Madrid, Spain
| | - Jose Luis Gil Salú
- Departamento de Neurocirugía, Hospital Universitario Puerta del Mar, Cádiz, Spain; Departamento de Neurocirugía, Hospital Universitario HM Montepríncipe, Madrid, Spain
| | - Alejandro Fernández Coello
- Departamento de Neurocirugía, Hospital Universitari Bellvitge, Barcelona, Spain; Departamento de Neurocirugía, Hospital Universitario HM Montepríncipe, Madrid, Spain
| | - Juan Carlos García Romero
- Departamento de Neurocirugía, Hospital Virgen del Rocío, Sevilla, Spain; Departamento de Neurocirugía, Hospital Universitario HM Montepríncipe, Madrid, Spain
| | - Angel Rodríguez de Lope Llorca
- Departamento de Neurocirugía, Hospital Virgen de la Salud, Toledo, Spain; Departamento de Neurocirugía, Hospital Universitario HM Montepríncipe, Madrid, Spain
| | - Sara García Duque
- Departamento de Neurocirugía, Hospital Universitario La Fe, Valencia, Spain; Departamento de Neurocirugía, Hospital Universitario HM Montepríncipe, Madrid, Spain
| | - Ricardo Díez Valle
- Departamento de Neurocirugía, Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain; Departamento de Neurocirugía, Hospital Universitario HM Montepríncipe, Madrid, Spain
| | - Jose Luis Narros Giménez
- Departamento de Neurocirugía, Hospital Virgen del Rocío, Sevilla, Spain; Departamento de Neurocirugía, Hospital Universitario HM Montepríncipe, Madrid, Spain
| | - Ricardo Prat Acín
- Departamento de Neurocirugía, Hospital Universitario La Fe, Valencia, Spain; Departamento de Neurocirugía, Hospital Universitario HM Montepríncipe, Madrid, Spain
| |
Collapse
|
|
13
|
Guo Y, Shen R, Wang F, Wang Y, Xia P, Wu R, Liu X, Ye W, Tian Y, Wang D. Carbon ion irradiation induces DNA damage in melanoma and optimizes the tumor microenvironment based on the cGAS-STING pathway. J Cancer Res Clin Oncol 2023:10.1007/s00432-023-04577-6. [PMID: 36745223 DOI: 10.1007/s00432-023-04577-6] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2022] [Accepted: 01/05/2023] [Indexed: 02/07/2023]
Abstract
PURPOSES Increased number of studies reveal the crucial role of the Cyclic GMP-AMP synthase/stimulator of interferon genes (cGAS/STING) pathway in anti-tumor immunity. In this study, we aim to explore the effect of cGAS/STING on tumor immune microenvironment of melanoma after carbon ion radiotherapy (CIRT) and the underlying mechanism. METHODS C57BL/6 mouse tumor models were used to evaluate the efficacy of different treatments (X-ray, carbon ion, PD-L1 inhibitor and combination therapies) on tumor growth and process. Mass cytometry was performed to assess tumor-infiltrating lymphocytes (TILs). DNA damage response (DDR) and cGAS/STING pathway were investigated by immunofluorescence-co-localization assays, γ-H2AX, P53-binding protein 1 (53BP1), Breast Cancer 1 (BRCA1), and cGAS measurements. RESULTS Carbon ion irradiation caused more DNA damages and cGAS-STING pathway activation compared with X-ray irradiation, and the former slowed the melanoma growth in syngeneic model. Although X-ray irradiation is not sensitive for melanoma treatment, carbon ion irradiation showed a significant anti-tumor effect for melanoma treatment. TILs analysis revealed that CIRT boosted the infiltration of natural killer (NK), CD4+, and CD8+ T cells, meanwhile increased the number of immune checkpoint (programmed death-1, PD-1, lymphocyte activation gene 3, LAG-3 and T-cell immunoglobulin and mucin domain-containing protein 3, TIM-3). Moreover, CIRT increased PD-L1 exposure on cell surface compared with X-ray group. Furthermore, CIRT combined with PD-L1 inhibitor therapy increased the number of T cells and NK cells in melanoma, and slowed the growth of melanoma compared with other therapies. CONCLUSIONS Our findings showed that CIRT displayed biological effects by increasing DNA damages of tumor cells and improving immunity in melanoma, which indicated that CIRT might be a potential synergetic treatment for radiotherapy and radioimmunotherapy in melanoma patients. Our works put forward a new insight to provide an effective strategy for melanoma therapy. These findings may help in the design of strategies on melanoma in clinical studies.
Collapse
Affiliation(s)
- Yanan Guo
- School of Basic Medical Sciences, Lanzhou University, Lanzhou, 73000, Gansu, China
| | - Rong Shen
- School of Basic Medical Sciences, Lanzhou University, Lanzhou, 73000, Gansu, China
| | - Fang Wang
- School of Basic Medical Sciences, Lanzhou University, Lanzhou, 73000, Gansu, China.,Medical Experimental Centre, Lanzhou University, Lanzhou, 73000, Gansu, China
| | - Yutong Wang
- School of Basic Medical Sciences, Lanzhou University, Lanzhou, 73000, Gansu, China
| | - Peng Xia
- School of Basic Medical Sciences, Lanzhou University, Lanzhou, 73000, Gansu, China
| | - Rile Wu
- School of Basic Medical Sciences, Lanzhou University, Lanzhou, 73000, Gansu, China
| | - Xiangwen Liu
- School of Basic Medical Sciences, Lanzhou University, Lanzhou, 73000, Gansu, China.,State Key Laboratory of Applied Organic Chemistry and Department of Chemistry, Lanzhou University, Lanzhou, 730000, China.,Department of Internal Medicine, Gansu Provincial Academic Institute for Medical Research, Lanzhou, 730050, China.,Medical Experimental Centre, Lanzhou University, Lanzhou, 73000, Gansu, China
| | - Weichun Ye
- State Key Laboratory of Applied Organic Chemistry and Department of Chemistry, Lanzhou University, Lanzhou, 730000, China.
| | - Yingxia Tian
- Department of Internal Medicine, Gansu Provincial Academic Institute for Medical Research, Lanzhou, 730050, China.
| | - Degui Wang
- School of Basic Medical Sciences, Lanzhou University, Lanzhou, 73000, Gansu, China. .,Medical Experimental Centre, Lanzhou University, Lanzhou, 73000, Gansu, China.
| |
Collapse
|
|
14
|
Lee JH, Wee CW. Treatment of Adult Gliomas: A Current Update. BRAIN & NEUROREHABILITATION 2022; 15:e24. [PMID: 36742086 PMCID: PMC9833488 DOI: 10.12786/bn.2022.15.e24] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2022] [Revised: 11/21/2022] [Accepted: 11/22/2022] [Indexed: 12/02/2022] Open
Abstract
Gliomas are the most common type of primary brain tumor in adults. Glioma treatment requires a multidisciplinary approach involving surgery, radiotherapy, and chemotherapy. Multiple trials have been conducted to establish the appropriate choice of treatment to achieve long-term survival and better quality of life. This review provides up-to-date evidence regarding treatment strategies for gliomas.
Collapse
Affiliation(s)
- Joo Ho Lee
- Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, Korea.,Department of Radiation Oncology, Seoul National University Hospital, Seoul, Korea
| | - Chan Woo Wee
- Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, Korea.,Department of Radiation Oncology, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul, Korea
| |
Collapse
|
|
15
|
Waltenberger M, Furkel J, Röhrich M, Salome P, Debus C, Tawk B, Gahlawat AW, Kudak A, Dostal M, Wirkner U, Schwager C, Herold-Mende C, Combs SE, König L, Debus J, Haberkorn U, Abdollahi A, Knoll M. The impact of tumor metabolic activity assessed by 18F-FET amino acid PET imaging in particle radiotherapy of high-grade glioma patients. Front Oncol 2022; 12:901390. [PMID: 36203443 PMCID: PMC9531169 DOI: 10.3389/fonc.2022.901390] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2022] [Accepted: 08/17/2022] [Indexed: 11/17/2022] Open
Abstract
Background Selective uptake of (18)F-fluoro-ethyl-tyrosine (18F-FET) is used in high-grade glioma (HGG) to assess tumor metabolic activity via positron emission tomography (PET). We aim to investigate its value for target volume definition, as a prognosticator, and associations with whole-blood transcriptome liquid biopsy (WBT lbx) for which we recently reported feasibility to mirror tumor characteristics and response to particle irradiation in recurrent HGG (rHGG). Methods 18F-FET-PET data from n = 43 patients with primary glioblastoma (pGBM) and n = 33 patients with rHGG were assessed. pGBM patients were irradiated with photons and sequential proton/carbon boost, and rHGG patients were treated with carbon re-irradiation (CIR). WBT (Illumina HumanHT-12 Expression BeadChips) lbx was available for n = 9 patients from the rHGG cohort. PET isocontours (40%–70% SUVmax, 10% steps) and MRI-based treatment volumes (MRIvol) were compared using the conformity index (CI) (pGBM, n = 16; rHGG, n = 27). Associations with WBT lbx data were tested on gene expression level and inferred pathways activity scores (PROGENy) and from transcriptome estimated cell fractions (CIBERSORT, xCell). Results In pGBM, median SUVmax was higher in PET acquired pre-radiotherapy (4.1, range (R) 1.5–7.8; n = 20) vs. during radiotherapy (3.3, R 1.5–5.7, n = 23; p = 0.03) and in non-resected (4.7, R 2.9–7.9; n = 11) vs. resected tumors (3.3, R 1.5–7.8, n = 32; p = 0.01). In rHGG, a trend toward higher SUVmax values in grade IV tumors was observed (p = 0.13). Median MRIvol was 32.34 (R 8.75–108.77) cm3 in pGBM (n = 16) and 20.77 (R 0.63–128.44) cm3 in rHGG patients (n = 27). The highest median CI was observed for 40% (pGBM, 0.31) and 50% (rHGG, 0.43, all tumors) isodose, with 70% (40%) isodose in grade III (IV) rHGG tumors (median CI, 0.38 and 0.49). High SUVmax was linked to shorter survival in pGBM (>3.3, p = 0.001, OR 6.0 [2.1–17.4]) and rHGG (>2.8, p = 0.02, OR 4.1 [1.2–13.9]). SUVmax showed associations with inferred monocyte fractions, hypoxia, and TGFbeta pathway activity and links to immune checkpoint gene expression from WBT lbx. Conclusion The benefits of 18F-FET-PET imaging on gross tumor volume (GTV) definition for particle radiotherapy warrant further evaluation. SUVmax might assist in prognostic stratification of HGG patients for particle radiotherapy, highlights heterogeneity in rHGG, and is positively associated with unfavorable signatures in peripheral whole-blood transcriptomes.
Collapse
Affiliation(s)
- Maria Waltenberger
- Department of Radiation Oncology, University Hospital of Heidelberg, Heidelberg, Germany
- Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany
- Heidelberg Institute for Radiation Oncology (HIRO), University Hospital of Heidelberg, Heidelberg, Germany
- Translational Radiation Oncology, German Cancer Consortium (DKTK), National Center for Tumor Diseases (NCT), German Cancer Research Center (DKFZ), Heidelberg, Germany
- Department of Radiation Oncology, Klinikum rechts der Isar, Technical University of Munich (TUM), Munich, Germany
| | - Jennifer Furkel
- Department of Radiation Oncology, University Hospital of Heidelberg, Heidelberg, Germany
- Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany
- Heidelberg Institute for Radiation Oncology (HIRO), University Hospital of Heidelberg, Heidelberg, Germany
- Translational Radiation Oncology, German Cancer Consortium (DKTK), National Center for Tumor Diseases (NCT), German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Manuel Röhrich
- Department of Nuclear Medicine, University Hospital Heidelberg, Heidelberg, Germany
| | - Patrick Salome
- Department of Radiation Oncology, University Hospital of Heidelberg, Heidelberg, Germany
- Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany
- Heidelberg Institute for Radiation Oncology (HIRO), University Hospital of Heidelberg, Heidelberg, Germany
- Translational Radiation Oncology, German Cancer Consortium (DKTK), National Center for Tumor Diseases (NCT), German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Charlotte Debus
- Department of Radiation Oncology, University Hospital of Heidelberg, Heidelberg, Germany
- Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany
- Heidelberg Institute for Radiation Oncology (HIRO), University Hospital of Heidelberg, Heidelberg, Germany
- Translational Radiation Oncology, German Cancer Consortium (DKTK), National Center for Tumor Diseases (NCT), German Cancer Research Center (DKFZ), Heidelberg, Germany
- Steinbuch Centre for Computing (SCC), Karlsruhe Institute of Technology (KIT), Eggenstein-Leopoldshafen, Germany
| | - Bouchra Tawk
- Department of Radiation Oncology, University Hospital of Heidelberg, Heidelberg, Germany
- Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany
- Heidelberg Institute for Radiation Oncology (HIRO), University Hospital of Heidelberg, Heidelberg, Germany
- Translational Radiation Oncology, German Cancer Consortium (DKTK), National Center for Tumor Diseases (NCT), German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Aoife Ward Gahlawat
- Department of Radiation Oncology, University Hospital of Heidelberg, Heidelberg, Germany
- Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany
- Heidelberg Institute for Radiation Oncology (HIRO), University Hospital of Heidelberg, Heidelberg, Germany
- Translational Radiation Oncology, German Cancer Consortium (DKTK), National Center for Tumor Diseases (NCT), German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Andreas Kudak
- Department of Radiation Oncology, University Hospital of Heidelberg, Heidelberg, Germany
- Heidelberg Institute for Radiation Oncology (HIRO), University Hospital of Heidelberg, Heidelberg, Germany
| | - Matthias Dostal
- Department of Radiation Oncology, University Hospital of Heidelberg, Heidelberg, Germany
- Heidelberg Institute for Radiation Oncology (HIRO), University Hospital of Heidelberg, Heidelberg, Germany
| | - Ute Wirkner
- Department of Radiation Oncology, University Hospital of Heidelberg, Heidelberg, Germany
- Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany
- Heidelberg Institute for Radiation Oncology (HIRO), University Hospital of Heidelberg, Heidelberg, Germany
- Translational Radiation Oncology, German Cancer Consortium (DKTK), National Center for Tumor Diseases (NCT), German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Christian Schwager
- Department of Radiation Oncology, University Hospital of Heidelberg, Heidelberg, Germany
- Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany
- Heidelberg Institute for Radiation Oncology (HIRO), University Hospital of Heidelberg, Heidelberg, Germany
- Translational Radiation Oncology, German Cancer Consortium (DKTK), National Center for Tumor Diseases (NCT), German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Christel Herold-Mende
- Department of Experimental Neurosurgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Stephanie E. Combs
- Department of Radiation Oncology, Klinikum rechts der Isar, Technical University of Munich (TUM), Munich, Germany
- German Cancer Consortium (DKTK), Partner Site Munich, Munich, Germany
- Institute of Radiation Medicine (IRM), Helmholtz Zentrum Munich, Munich, Germany
| | - Laila König
- Heidelberg Institute for Radiation Oncology (HIRO), University Hospital of Heidelberg, Heidelberg, Germany
- Translational Radiation Oncology, German Cancer Consortium (DKTK), National Center for Tumor Diseases (NCT), German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Jürgen Debus
- Department of Radiation Oncology, University Hospital of Heidelberg, Heidelberg, Germany
- Heidelberg Institute for Radiation Oncology (HIRO), University Hospital of Heidelberg, Heidelberg, Germany
- Translational Radiation Oncology, German Cancer Consortium (DKTK), National Center for Tumor Diseases (NCT), German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Uwe Haberkorn
- Department of Nuclear Medicine, University Hospital Heidelberg, Heidelberg, Germany
| | - Amir Abdollahi
- Department of Radiation Oncology, University Hospital of Heidelberg, Heidelberg, Germany
- Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany
- Heidelberg Institute for Radiation Oncology (HIRO), University Hospital of Heidelberg, Heidelberg, Germany
- Translational Radiation Oncology, German Cancer Consortium (DKTK), National Center for Tumor Diseases (NCT), German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Maximilian Knoll
- Department of Radiation Oncology, University Hospital of Heidelberg, Heidelberg, Germany
- Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany
- Heidelberg Institute for Radiation Oncology (HIRO), University Hospital of Heidelberg, Heidelberg, Germany
- Translational Radiation Oncology, German Cancer Consortium (DKTK), National Center for Tumor Diseases (NCT), German Cancer Research Center (DKFZ), Heidelberg, Germany
- *Correspondence: Maximilian Knoll,
| |
Collapse
|
|
16
|
Leone A, Colamaria A, Fochi NP, Sacco M, Landriscina M, Parbonetti G, de Notaris M, Coppola G, De Santis E, Giordano G, Carbone F. Recurrent Glioblastoma Treatment: State of the Art and Future Perspectives in the Precision Medicine Era. Biomedicines 2022; 10:1927. [PMID: 36009473 PMCID: PMC9405902 DOI: 10.3390/biomedicines10081927] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2022] [Revised: 08/04/2022] [Accepted: 08/05/2022] [Indexed: 12/20/2022] Open
Abstract
Current treatment guidelines for the management of recurrent glioblastoma (rGBM) are far from definitive, and the prognosis remains dismal. Despite recent advancements in the pharmacological and surgical fields, numerous doubts persist concerning the optimal strategy that clinicians should adopt for patients who fail the first lines of treatment and present signs of progressive disease. With most recurrences being located within the margins of the previously resected lesion, a comprehensive molecular and genetic profiling of rGBM revealed substantial differences compared with newly diagnosed disease. In the present comprehensive review, we sought to examine the current treatment guidelines and the new perspectives that polarize the field of neuro-oncology, strictly focusing on progressive disease. For this purpose, updated PRISMA guidelines were followed to search for pivotal studies and clinical trials published in the last five years. A total of 125 articles discussing locoregional management, radiotherapy, chemotherapy, and immunotherapy strategies were included in our analysis, and salient findings were critically summarized. In addition, an in-depth description of the molecular profile of rGBM and its distinctive characteristics is provided. Finally, we integrate the above-mentioned evidence with the current guidelines published by international societies, including AANS/CNS, EANO, AIOM, and NCCN.
Collapse
Affiliation(s)
- Augusto Leone
- Department of Neurosurgery, Städtisches Klinikum Karlsruhe, 76133 Karlsruhe, Germany
- Department of Neurosurgery, Charité Universitätsmedizin Berlin, 10117 Berlin, Germany
| | | | - Nicola Pio Fochi
- Department of Neurosurgery, University of Foggia, 71122 Foggia, Italy
| | - Matteo Sacco
- Department of Neurosurgery, Riuniti Hospital, 71122 Foggia, Italy
| | - Matteo Landriscina
- Unit of Medical
Oncology and Biomolecular Therapy, Department of Medical and Surgical
Sciences, University of Foggia, 71122 Foggia, Italy
| | | | - Matteo de Notaris
- Department of Neurosurgery, “Rummo” Hospital, 82100 Benevento, Italy
| | - Giulia Coppola
- Department of Radiological, Oncological and Pathological Sciences, Sapienza University of Rome, 00185 Roma, Italy
| | - Elena De Santis
- Department of Anatomical Histological Forensic Medicine and Orthopedic Sciences, Sapienza University of Rome, 00185 Roma, Italy
| | - Guido Giordano
- Unit of Medical
Oncology and Biomolecular Therapy, Department of Medical and Surgical
Sciences, University of Foggia, 71122 Foggia, Italy
| | - Francesco Carbone
- Department of Neurosurgery, Städtisches Klinikum Karlsruhe, 76133 Karlsruhe, Germany
- Department of Neurosurgery, University of Foggia, 71122 Foggia, Italy
| |
Collapse
|
|
17
|
Frosina G. Improving control of high‐grade glioma by ultra‐hyper‐fractionated radiotherapy. J Neurosci Res 2022; 100:933-946. [DOI: 10.1002/jnr.25030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2021] [Revised: 10/05/2021] [Accepted: 12/13/2021] [Indexed: 11/11/2022]
Affiliation(s)
- Guido Frosina
- Mutagenesis & Cancer Prevention Unit IRCCS Ospedale Policlinico San Martino Genova Italy
| |
Collapse
|
|
18
|
Ma Q, Yang T. E2F transcription factor 1/small nucleolar RNA host gene 18/microRNA-338-5p/forkhead box D1: an important regulatory axis in glioma progression. Bioengineered 2021; 13:418-430. [PMID: 34937497 PMCID: PMC8805867 DOI: 10.1080/21655979.2021.2005990] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
Abstract
This study aims to probe the biological functions of long non-coding RNA small nucleolar RNA host gene 18 (SNHG18) on glioma cells and its underlying mechanism. In this study, SNHG18 expression in glioma tissues was quantified employing GEPIA database; quantitative real-time PCR was adopted to examine the expressions of SNHG18, microRNA-338-5p (miR-338-5p) and forkhead box D1 (FOXD1) mRNA in glioma tissues and cell lines; cell proliferation, migration and invasion were detected utilizing cell counting kit-8, EdU and Transwell assays; Western blot was utilized to quantify the protein expressions of E-cadherin, N-cadherin, Vimentin and FOXD1; dual-luciferase reporter gene and RNA immunoprecipitation experiments were utilized to validate the targeting relationships between SNHG18 and miR-338-5p, as well as miR-338-5p and FOXD1 mRNA 3ʹUTR; dual-luciferase reporter gene and chromatin immunoprecipitation assays were utilized to verify the binding of E2F transcription factor 1 (E2F1) to the SNHG18 promoter region. It was revealed that, SNHG18 expression in glioma was up-regulated and associated with unfavorable prognosis of the patients; knockdown of SNHG18 repressed the malignant biological behaviors of glioma cells, enhanced E-cadherin expression and repressed N-cadherin and Vimentin expressions. MiR-338-5p was a target of SNHG18, and SNHG18 promoted the expression of FOXD1 by decoying miR-338-5p. Additionally, E2F1 could bind to the promoter of SNHG18 to elevate its expression. In conclusion, SNHG18 accelerates glioma progression via regulating the miR-338-5p/FOXD1 axis.
Collapse
Affiliation(s)
- Quanfeng Ma
- Department of Neurosurg, Tianjin Huanhu Hospital, Tianjin Key Laboratory of Cerebral Vascular and Neurodegenerative Diseases, Tianjin Neurosurg Institution, Tianjin China
| | - Tianhao Yang
- Department of Radiology, Tianjin Huanhu Hospital, Tianjin Key Laboratory of Cerebral Vascular and Neurodegenerative Diseases, Tianjin China
| |
Collapse
|
|
19
|
Galanis E, Wen PY, de Groot JF, Weller M. Isocitrate Dehydrogenase Wild-type Glial Tumors, Including Glioblastoma. Hematol Oncol Clin North Am 2021; 36:113-132. [PMID: 34756799 DOI: 10.1016/j.hoc.2021.08.007] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
Isocitrate dehydrogenase (IDH) 1 and 2 mutations represent essential components for the diagnosis of diffuse astrocytic tumors and oligodendroglioma. IDH wild-type glial tumors include a wide spectrum of tumors with differences in prognosis and recommended therapeutic approaches. Tumors characterized as molecular glioblastoma in the World Health Organization 2021 classification should be treated according to the glioblastoma therapeutic principles and included in glioblastoma trials. Improving on existing treatments options including targeted and immunotherapy approaches is imperative for most patients with IDH wild-type glial tumors, and enrollment in clinical trials is encouraged.
Collapse
Affiliation(s)
- Evanthia Galanis
- Department of Oncology, Mayo Clinic, 200 First Street Southwest, Rochester, MN 55905, USA.
| | - Patrick Y Wen
- Neuro-oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Shields Warren 430 D, Boston, MA 02215, USA
| | - John F de Groot
- Department of Neurological Surgery, University of California San Francisco, 505 Parnassus Avenue, San Francisco, CA 94143, USA
| | - Michael Weller
- Department of Neurology, University Hospital and University of Zurich, Frauenklinikstrasse 26, Zurich 8091, Switzerland
| |
Collapse
|
|
20
|
Li M, Dou W, Lin Y, Li Q, Xu H, Zhang D. Evidence Mapping of Proton Therapy, Heavy Ion Therapy, and Helical Tomotherapy for Gastric Cancer. Oncol Res Treat 2021; 44:700-709. [PMID: 34695829 DOI: 10.1159/000518997] [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: 03/07/2021] [Accepted: 08/12/2021] [Indexed: 11/19/2022]
Abstract
PURPOSE This study aimed to systematically present application situation and therapeutic effect of proton therapy (PT), heavy ion therapy, and helical tomotherapy (TOMO) for gastric cancer (GC), and to find gaps of existing studies. METHODS PubMed, EMBASE, the Cochrane Library, Web of Science, and Chinese Biological Medical Database were searched. Tables, bubble plot, and heat map were conducted to display results. RESULTS Fourteen studies were included. About PT, 7 single-arm studies showed median overall survival (OS) within 2-66 months and 1 study reported 40% of patients happened moderate degree of radiation gastritis. About TOMO, 1 study reported longer median OS and progression-free survival, lower occurrence of Grade III toxicity, and late toxicity compared to 3D-CRT, while another study remained neutral. About heavy ion therapy, there was no clinical study was found. CONCLUSIONS Existing studies presented good clinic treatment effect about PT and TOMO for GC, and furthermore clinical studies are needed.
Collapse
Affiliation(s)
- Muyang Li
- The Second Clinical Medical College of Lanzhou University, Lanzhou, China
| | - Wenshan Dou
- The Second Clinical Medical College of Lanzhou University, Lanzhou, China
| | - Yimin Lin
- The Second Clinical Medical College of Lanzhou University, Lanzhou, China
| | - Qianqian Li
- The Second Clinical Medical College of Lanzhou University, Lanzhou, China
| | - Huimei Xu
- Department of Gastroenterology, Lanzhou University Second Hospital, Lanzhou, China
| | - Dekui Zhang
- Department of Gastroenterology, Lanzhou University Second Hospital, Lanzhou, China
| |
Collapse
|
|
21
|
Hutóczki G, Virga J, Birkó Z, Klekner A. Novel Concepts of Glioblastoma Therapy Concerning Its Heterogeneity. Int J Mol Sci 2021; 22:ijms221810005. [PMID: 34576168 PMCID: PMC8470251 DOI: 10.3390/ijms221810005] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2021] [Revised: 09/05/2021] [Accepted: 09/08/2021] [Indexed: 12/28/2022] Open
Abstract
Although treatment outcomes of glioblastoma, the most malignant central nervous system (CNS) tumor, has improved in the past decades, it is still incurable, and survival has only slightly improved. Advances in molecular biology and genetics have completely transformed our understanding of glioblastoma. Multiple classifications and different diagnostic methods were made according to novel molecular markers. Discovering tumor heterogeneity only partially explains the ineffectiveness of current anti-proliferative therapies. Dynamic heterogeneity secures resistance to combined oncotherapy. As tumor growth proceeds, new therapy-resistant sub clones emerge. Liquid biopsy is a new and promising diagnostic tool that can step up with the dynamic genetic change. Getting a 'real-time' picture of a specific tumor, anti-invasion and multi-target treatment can be designed. During invasion to the peri-tumoral brain tissue, glioma cells interact with the extracellular matrix components. The expressional levels of these matrix molecules give a characteristic pattern, the invasion spectrum, which possess vast diagnostical, predictive and prognostic information. It is a huge leap forward combating tumor heterogeneity and searching for novel therapies. Using the invasion spectrum of a tumor sample is a novel tool to distinguish between histological subtypes, specifying the tumor grades or different prognostic groups. Moreover, new therapeutic methods and their combinations are under trial. These are crucial steps towards personalized oncotherapy.
Collapse
Affiliation(s)
- Gábor Hutóczki
- Department of Neurosurgery, University of Debrecen, H-4032 Debrecen, Hungary;
- Correspondence:
| | - József Virga
- Department of Oncology, University of Debrecen, H-4032 Debrecen, Hungary;
| | - Zsuzsanna Birkó
- Department of Human Genetics, University of Debrecen, H-4032 Debrecen, Hungary;
| | - Almos Klekner
- Department of Neurosurgery, University of Debrecen, H-4032 Debrecen, Hungary;
| |
Collapse
|
|
22
|
Wang H, Chen W, Wu G, Kong J, Yuan S, Chen L. A Magnetic T7 Peptide&AS1411 Aptamer-Modified Microemulsion for Triple Glioma-Targeted Delivery of Shikonin and Docetaxel. J Pharm Sci 2021; 110:2946-2954. [PMID: 33785350 DOI: 10.1016/j.xphs.2021.03.018] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2021] [Revised: 03/24/2021] [Accepted: 03/24/2021] [Indexed: 01/17/2023]
Abstract
Glioma-targeted drug delivery is a hugely challenging task because of the multibarrier in the brain. In this study, we report a magnetic T7 peptide&AS1411 aptamer-modified microemulsion for triple glioma-targeted delivery of shikonin and docetaxel (Fe3O4@T7/AS1411/DTX&SKN-M). Such a system comprises two tumor-targeted ligands (T7 peptide and AS1411 aptamer), ultra-small superparamagnetic iron oxide nanoparticle (Fe3O4), and shikonin&docetaxel-coloaded microemulsion (SKN&DTX-M). Fe3O4@T7/AS1411/DTX&SKN-M is capable of stably circulating in the blood, accumulating around the brain under an external magnetic field, distributing inside the glioma via the affinity to nucleolin/transferrin receptor, and retarding the growth of orthotopic glioma. Fe3O4@T7/AS1411/DTX&SKN-M encapsulated Fe3O4 nanoparticles in the core to obtain the superparamagnetism, which did not influence the main surface properties. Introducing 6% (wt%) of DSPE-PEG2000-T7 and 180 nM of AS1411 collaboratively enhanced the murine glioma (G422) cellular uptake of Fe3O4@T7/AS1411/DTX&SKN-M and thereby achieved the strongest antiproliferation among all the groups. Notably, the drug distribution at the brain sites of orthotopic Luc-G422 glioma tumor-bearing nude mice treated with Fe3O4@T7/AS1411/DTX&SKN-M was overwhelming among all the treatments. Most importantly, Fe3O4@T7/AS1411/DTX&SKN-M not only significantly reduced the luminescence signal at the brain areas of orthotopic Luc-G422 glioma mice but also prolonged the overall survival period. The enhancement of anti-glioma efficacy was associated with down-regulating the population of CD133- and CD44-positive cells within the tumors. In summary, such a triple glioma-targeted delivery of shikonin and docetaxel using combinational magnetism and T7/AS1411 modification strategies provides a promising method for synergistic and precise glioma therapy.
Collapse
Affiliation(s)
- Hong Wang
- Department of Neurosurgery, School of Medicine, Zhongda Hospital, Southeast University, Nanjing 210009, People's Republic of China
| | - Wanghao Chen
- Department of Neurosurgery, School of Medicine, Zhongda Hospital, Southeast University, Nanjing 210009, People's Republic of China
| | - Guojian Wu
- Department of Neurosurgery, School of Medicine, Zhongda Hospital, Southeast University, Nanjing 210009, People's Republic of China
| | - Jun Kong
- Department of Neurosurgery, School of Medicine, Zhongda Hospital, Southeast University, Nanjing 210009, People's Republic of China
| | - Shaofei Yuan
- Department of Medical Oncology, The Third Affiliated Hospital of Wenzhou Medical University, Rui'an 325200, People's Republic of China.
| | - Lukui Chen
- Department of Neurosurgery, School of Medicine, Zhongda Hospital, Southeast University, Nanjing 210009, People's Republic of China; Department of Neurosurgery, Cancer Center, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510315, People's Republic of China.
| |
Collapse
|
|
23
|
Bennan ABA, Unkelbach J, Wahl N, Salome P, Bangert M. Joint Optimization of Photon-Carbon Ion Treatments for Glioblastoma. Int J Radiat Oncol Biol Phys 2021; 111:559-572. [PMID: 34058258 DOI: 10.1016/j.ijrobp.2021.05.126] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2020] [Revised: 04/09/2021] [Accepted: 05/21/2021] [Indexed: 12/14/2022]
Abstract
PURPOSE Carbon ions are radiobiologically more effective than photons and are beneficial for treating radioresistant gross tumor volumes (GTV). However, owing to a reduced fractionation effect, they may be disadvantageous for treating infiltrative tumors, in which healthy tissue inside the clinical target volume (CTV) must be protected through fractionation. This work addresses the question: What is the ideal combined photon-carbon ion fluence distribution for treating infiltrative tumors given a specific fraction allocation between photons and carbon ions? METHODS AND MATERIALS We present a method to simultaneously optimize sequentially delivered intensity modulated photon (IMRT) and carbon ion (CIRT) treatments based on cumulative biological effect, incorporating both the variable relative biological effect of carbon ions and the fractionation effect within the linear quadratic model. The method is demonstrated for 6 glioblastoma patients in comparison with the current clinical standard of independently optimized CIRT-IMRT plans. RESULTS Compared with the reference plan, joint optimization strategies yield inhomogeneous photon and carbon ion dose distributions that cumulatively deliver a homogeneous biological effect distribution. In the optimal distributions, the dose to CTV is mostly delivered by photons and carbon ions are restricted to the GTV with variations depending on tumor size and location. Improvements in conformity of high-dose regions are reflected by a mean EQD2 reduction of 3.29 ± 1.22 Gy in a dose fall-off margin around the CTV. Carbon ions may deliver higher doses to the center of the GTV, and photon contributions are increased at interfaces with CTV and critical structures. This results in a mean EQD2 reduction of 8.3 ± 2.28 Gy, in which the brain stem abuts the target volumes. CONCLUSIONS We have developed a biophysical model to optimize combined photon-carbon ion treatments. For 6 glioblastoma patient cases, we show that our approach results in a more targeted application of carbon ions that (1) reduces dose in normal tissues within the target volume, which can only be protected through fractionation; and (2) boosts central target volume regions to reduce integral dose. Joint optimization of IMRT-CIRT treatments enable the exploration of a new spectrum of plans that can better address physical and radiobiological treatment planning challenges.
Collapse
Affiliation(s)
- Amit Ben Antony Bennan
- Department of Medical Physics in Radiation Oncology, German Cancer Research Center, Heidelberg, Germany; Medical Faculty, Heidelberg University, Heidelberg, Germany; Heidelberg Institute for Radiation Oncology (HIRO), Heidelberg, Germany.
| | - Jan Unkelbach
- Department of Radiation Oncology, University Hospital Zurich, Switzerland
| | - Niklas Wahl
- Department of Medical Physics in Radiation Oncology, German Cancer Research Center, Heidelberg, Germany; Heidelberg Institute for Radiation Oncology (HIRO), Heidelberg, Germany
| | - Patrick Salome
- Medical Faculty, Heidelberg University, Heidelberg, Germany; Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center (DKFZ)
| | - Mark Bangert
- Department of Medical Physics in Radiation Oncology, German Cancer Research Center, Heidelberg, Germany
| |
Collapse
|
|
24
|
Xie Y, Han Y, Zhang X, Ma H, Li L, Yu R, Liu H. Application of New Radiosensitizer Based on Nano-Biotechnology in the Treatment of Glioma. Front Oncol 2021; 11:633827. [PMID: 33869019 PMCID: PMC8044949 DOI: 10.3389/fonc.2021.633827] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2020] [Accepted: 03/03/2021] [Indexed: 12/26/2022] Open
Abstract
Glioma is the most common intracranial malignant tumor, and its specific pathogenesis has been unclear, which has always been an unresolved clinical problem due to the limited therapeutic window of glioma. As we all know, surgical resection, chemotherapy, and radiotherapy are the main treatment methods for glioma. With the development of clinical trials and traditional treatment techniques, radiotherapy for glioma has increasingly exposed defects in the treatment effect. In order to improve the bottleneck of radiotherapy for glioma, people have done a lot of work; among this, nano-radiosensitizers have offered a novel and potential treatment method. Compared with conventional radiotherapy, nanotechnology can overcome the blood–brain barrier and improve the sensitivity of glioma to radiotherapy. This paper focuses on the research progress of nano-radiosensitizers in radiotherapy for glioma.
Collapse
Affiliation(s)
- Yandong Xie
- Institute of Nervous System Diseases, Xuzhou Medical University, Xuzhou, China.,Department of Neurosurgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.,Department of Neurosurgery, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, China
| | - Yuhan Han
- Institute of Nervous System Diseases, Xuzhou Medical University, Xuzhou, China.,Department of Neurosurgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.,Department of Neurosurgery, Suqian First People's Hospital, Suqian, China
| | - Xuefeng Zhang
- Institute of Nervous System Diseases, Xuzhou Medical University, Xuzhou, China
| | - Hongwei Ma
- Institute of Nervous System Diseases, Xuzhou Medical University, Xuzhou, China
| | - Linfeng Li
- Institute of Nervous System Diseases, Xuzhou Medical University, Xuzhou, China
| | - Rutong Yu
- Institute of Nervous System Diseases, Xuzhou Medical University, Xuzhou, China.,Department of Neurosurgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
| | - Hongmei Liu
- Institute of Nervous System Diseases, Xuzhou Medical University, Xuzhou, China.,Department of Neurosurgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
| |
Collapse
|
|
25
|
Magnetic Hyperthermia as an adjuvant cancer therapy in combination with radiotherapy versus radiotherapy alone for recurrent/progressive glioblastoma: a systematic review. J Neurooncol 2021; 152:419-428. [PMID: 33713248 DOI: 10.1007/s11060-021-03729-3] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2021] [Accepted: 02/27/2021] [Indexed: 02/07/2023]
Abstract
INTRODUCTION Hyperthermia therapy (HT) is a recognized treatment modality, that can sensitize tumors to the effects of radiotherapy (RT) and chemotherapy by heating up tumor cells to 40-45 °C. The advantages of noninvasive inductive magnetic hyperthermia (MH) over RT or chemotherapy in the treatment of recurrent/progressive glioma have been confirmed by several clinical trials. Thus, here we have conducted a systematic review to provide a concise, albeit brief, account of the currently available literature regarding this topic. METHODS Five databases, PubMed/Medline, Embace, Ovid, WOS, and Scopus, were investigated to identify clinical studies comparing overall survival (OS) following RT/chemotherapy versus RT/chemotherapy + MH. RESULTS Eleven articles were selected for this systematic review, including reports on 227 glioma patients who met the study inclusion criteria. The papers included in this review comprised nine pilot clinical trials, one non-randomized clinical trial, and one retrospective investigation. As the clinical trials suggested, MH improved OS in primary glioblastoma (GBM), however, in the case of recurrent glioblastoma, no significant change in OS was reported. All 11 studies ascertained that no major side effects were observed during MH therapy. CONCLUSION Our systematic review indicates that MH therapy as an adjuvant for RT could result in improved survival, compared to the therapeutic outcomes achieved with RT alone in GBM, especially by intratumoral injection of magnetic nanoparticles. However, heterogeneity in the methodology of the most well-known studies, and differences in the study design may significantly limit the extent to which conclusions can be drawn. Thus, further investigations are required to shed more light on the efficacy of MH therapy as an adjuvant treatment modality in GBM.
Collapse
|
|
26
|
Ebner DK, Frank SJ, Inaniwa T, Yamada S, Shirai T. The Emerging Potential of Multi-Ion Radiotherapy. Front Oncol 2021; 11:624786. [PMID: 33692957 PMCID: PMC7937868 DOI: 10.3389/fonc.2021.624786] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2020] [Accepted: 01/04/2021] [Indexed: 12/26/2022] Open
Abstract
Research into high linear energy transfer (LET) radiotherapy now spans over half a century, beginning with helium and deuteron treatment in 1952 and today ranging from fast neutrons to carbon-ions. Owing to pioneering work initially in the United States and thereafter in Germany and Japan, increasing focus is on the carbon-ion beam: 12 centers are in operation, with five under construction and three in planning. While the carbon-ion beam has demonstrated unique and promising suitability in laboratory and clinical trials toward the hypofractionated treatment of hypoxic and/or radioresistant cancer, substantial developmental potential remains. Perhaps most notable is the ability to paint LET in a tumor, theoretically better focusing damage delivery within the most resistant areas. However, the technique may be limited in practice by the physical properties of the beams themselves. A heavy-ion synchrotron may provide irradiation with multiple heavy-ions: carbon, helium, and oxygen are prime candidates. Each ion varies in LET distribution, and so a methodology combining the use of multiple ions into a uniform LET distribution within a tumor may allow for even greater treatment potential in radioresistant cancer.
Collapse
Affiliation(s)
- Daniel K Ebner
- National Institute of Radiological Science (NIRS), National Institutes of Quantum and Radiological Science and Technology (QST), Chiba, Japan
| | - Steven J Frank
- Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Taku Inaniwa
- National Institute of Radiological Science (NIRS), National Institutes of Quantum and Radiological Science and Technology (QST), Chiba, Japan
| | - Shigeru Yamada
- National Institute of Radiological Science (NIRS), National Institutes of Quantum and Radiological Science and Technology (QST), Chiba, Japan
| | - Toshiyuki Shirai
- National Institute of Radiological Science (NIRS), National Institutes of Quantum and Radiological Science and Technology (QST), Chiba, Japan
| |
Collapse
|
|
27
|
Nordmann NJ, Michael AP. 5-Aminolevulinic acid radiodynamic therapy for treatment of high-grade gliomas: A systematic review. Clin Neurol Neurosurg 2020; 201:106430. [PMID: 33360951 DOI: 10.1016/j.clineuro.2020.106430] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2020] [Revised: 12/09/2020] [Accepted: 12/10/2020] [Indexed: 01/22/2023]
Abstract
INTRODUCTION Radiodynamic therapy (RDT) involves administration of a radiosensitizing agent and its subsequent activation by ionizing radiation for destruction of neoplastic cells. MATERIALS AND METHODS A comprehensive evaluation of the literature was performed to review the history of RDT using porphyrins for solid tumors, the cellular mechanisms of action, immunomodulatory effects, and both preclinical and clinical studies for use in high-grade gliomas (HGGs). This manuscript was prepared in accordance with the PRISMA guidelines. RESULTS A total of 271 articles were considered for initial review. After removal of duplicates, articles not unrelated to specific topic, and exclusion of commentary articles, a total of 11 articles were subject to full analysis that included in vivo, in vitro, and human studies. Porphyrins such as 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX) selectively accumulate in neoplastic cells and are currently used for fluorescent-guided surgical resection and photodynamic therapy (PDT) of HGG and other brain tumors. 5-ALA is also shown to act as a radiosensitizer by increasing oxidative stress in neoplastic cell mitochondria and enhancing the host immune response. Postoperative radiation therapy is currently the standard of care for treatment of HGG. CONCLUSION RDT remains a promising adjuvant therapy for HGGs and requires further investigation. Clinical trials of 5-ALA RDT for HGG are needed to evaluate the optimum timing, dosing and effectiveness.
Collapse
Affiliation(s)
- Nathan J Nordmann
- Division of Neurosurgery, Neuroscience Institute, Southern Illinois University School of Medicine. P.O. Box 19638, Springfield, IL, 62794-9638, United States
| | - Alex P Michael
- Division of Neurosurgery, Neuroscience Institute, Southern Illinois University School of Medicine. P.O. Box 19638, Springfield, IL, 62794-9638, United States.
| |
Collapse
|
|
28
|
EANO guidelines on the diagnosis and treatment of diffuse gliomas of adulthood. Nat Rev Clin Oncol 2020; 18:170-186. [PMID: 33293629 PMCID: PMC7904519 DOI: 10.1038/s41571-020-00447-z] [Citation(s) in RCA: 1037] [Impact Index Per Article: 207.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/19/2020] [Indexed: 01/16/2023]
Abstract
In response to major changes in diagnostic algorithms and the publication of mature results from various large clinical trials, the European Association of Neuro-Oncology (EANO) recognized the need to provide updated guidelines for the diagnosis and management of adult patients with diffuse gliomas. Through these evidence-based guidelines, a task force of EANO provides recommendations for the diagnosis, treatment and follow-up of adult patients with diffuse gliomas. The diagnostic component is based on the 2016 update of the WHO Classification of Tumors of the Central Nervous System and the subsequent recommendations of the Consortium to Inform Molecular and Practical Approaches to CNS Tumour Taxonomy — Not Officially WHO (cIMPACT-NOW). With regard to therapy, we formulated recommendations based on the results from the latest practice-changing clinical trials and also provide guidance for neuropathological and neuroradiological assessment. In these guidelines, we define the role of the major treatment modalities of surgery, radiotherapy and systemic pharmacotherapy, covering current advances and cognizant that unnecessary interventions and expenses should be avoided. This document is intended to be a source of reference for professionals involved in the management of adult patients with diffuse gliomas, for patients and caregivers, and for health-care providers. Herein, the European Association of Neuro-Oncology (EANO) provides recommendations for the diagnosis, treatment and follow-up of adult patients with diffuse gliomas. These evidence-based guidelines incorporate major changes in diagnostic algorithms based on the 2016 update of the WHO Classification of Tumors of the Central Nervous System as well as on evidence from recent large clinical trials.
Collapse
|
|
29
|
Venkatesulu BP, Giridhar P, Malouf TD, Trifletti DM, Krishnan S. A systematic review of the role of carbon ion radiation therapy in recurrent rectal cancer. Acta Oncol 2020; 59:1218-1223. [PMID: 32476538 DOI: 10.1080/0284186x.2020.1769184] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
BACKGROUND Colorectal cancer is the fourth leading cause of cancer-associated death in the world. The 5-year local recurrence rates in patients undergoing multimodality therapy are approximately 5-10%. The standard approach to treat locally recurrent rectal is re-irradiation followed by surgical resection. Recent reports have suggested that the treatment outcomes with carbon ion radiation therapy (CIRT) in recurrent rectal cancer are promising and have superior results compared to photon therapy. Hence, we performed a systematic review to evaluate the patterns of care and treatment outcomes of recurrent rectal cancer patients treated with CIRT. METHODOLOGY We performed a systematic search to identify the articles that reported on CIRT use in recurrent rectal cancer. RESULTS Systematic search of PubMed and Cochrane Central resulted in 98 abstracts. Eight studies fulfilled the predefined inclusion criteria. Among eight studies, one study is a prospective phase I/II study done in Japan; three prospective studies are ongoing (PANDORA-01 trial, HIMAT1351trial, and a phase II study of reirradiation for prior CIRT), and five studies are institutional reports on role of CIRT. These studies were predominantly reported from Japan and Germany. All reports except one were performed in patients who have not received prior radiation. The most commonly utilized treatment prescription was 73.4 Gy (RBE) in 16 fractions over 4 weeks in patients without any prior history of radiation and 36 Gy in 12 fractions over 3 weeks at 3 Gy per fraction in patients with prior photon radiation to the pelvis. There is one ongoing trial assessing the role of carbon ion re-irradiation in patients who had prior CIRT for rectal cancer. CONCLUSION CIRT holds immense promise in improving outcomes in locally recurrent rectal cancer. There is a need for more multi-institutional prospective clinical trials to assess the role of CIRT.
Collapse
Affiliation(s)
| | - Prashanth Giridhar
- Department of Radiation Oncology, All India Institute of medical sciences, New Delhi, India
| | - Timothy D. Malouf
- Department of Radiation Oncology, Mayo Clinic Florida, Jacksonville, FL, USA
| | - Daniel M. Trifletti
- Department of Radiation Oncology, Mayo Clinic Florida, Jacksonville, FL, USA
| | - Sunil Krishnan
- Department of Radiation Oncology, Mayo Clinic Florida, Jacksonville, FL, USA
| |
Collapse
|
|
30
|
Li Y, Deng G, Qi Y, Zhang H, Gao L, Jiang H, Ye Z, Liu B, Chen Q. Bioinformatic Profiling of Prognosis-Related Genes in Malignant Glioma Microenvironment. Med Sci Monit 2020; 26:e924054. [PMID: 32843610 PMCID: PMC7780890 DOI: 10.12659/msm.924054] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Gliomas are the most common primary tumors of the brain and spinal cord. The tumor microenvironment (TME) is the cellular environment in which tumors exist. This study aimed to identify the role of the TME and the effects of genes involved in the TME of malignant glioma. MATERIAL AND METHODS The ESTIMATE algorithms in the R package were used to calculate the immune and stromal scores of samples in the TCGA and GSE4290 datasets. The associations of stromal and immune scores with clinicopathological characteristics and overall survival of malignant glioma patients were assessed by analysis of variance and Kaplan-Meier analysis. Differentially expressed genes (DEGs) were obtained through the median immune and stromal score using the R package "limma". Functional enrichment analysis and the PPI network MCODE were used to analyze DEGs. RESULTS Increased immune and stromal scores were closely related with advanced glioma grade and poor prognosis (all P<0.01). In total, 558 DEGs were found and most were related to tumor prognosis. Functional enrichment analysis showed that DEGs were associated with cell-matrix regulation and immune response. Four hub modules related to tumor angiogenesis, collagen formation, and immune response were found and analyzed. Previously overlooked microenvironment-related genes such as LAMB1, FN1, ACTN1, TRIM, SERPINH1, CYBA, LAIR1, and LILRB2 showed prognostic values in malignant glioma patients. CONCLUSIONS The glioma stromal/immune scores are closely related to glioma grade, histology, and survival time. Some glioma microenvironment-related genes including LAMB1, FN1, ACTN1, TRIM6, SERPINH1, CYBA, LAIR1, and LILRB2 show prognostic values in malignant gliomas and serve as potential biomarkers.
Collapse
Affiliation(s)
- Yong Li
- Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, China (mainland)
| | - Gang Deng
- Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, China (mainland)
| | - Yangzhi Qi
- Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, China (mainland)
| | - Huikai Zhang
- Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, China (mainland)
| | - Lun Gao
- Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, China (mainland)
| | - Hongxiang Jiang
- Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, China (mainland)
| | - Zhang Ye
- Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, China (mainland)
| | - Baohui Liu
- Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, China (mainland)
| | - Qianxue Chen
- Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, China (mainland)
| |
Collapse
|
|
31
|
Palma A, Grande S, Ricci-Vitiani L, Luciani AM, Buccarelli M, Biffoni M, Dini V, Cirrone GAP, Ciocca M, Guidoni L, Pallini R, Viti V, Rosi A. Different Mechanisms Underlie the Metabolic Response of GBM Stem-Like Cells to Ionizing Radiation: Biological and MRS Studies on Effects of Photons and Carbon Ions. Int J Mol Sci 2020; 21:ijms21145167. [PMID: 32708312 PMCID: PMC7404344 DOI: 10.3390/ijms21145167] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2020] [Revised: 07/18/2020] [Accepted: 07/20/2020] [Indexed: 12/13/2022] Open
Abstract
Glioblastoma multiforme (GBM) is a malignant primary brain tumor with very poor prognosis, high recurrence rate, and failure of chemo-radiotherapy, mainly due to a small fraction of cells with stem-like properties (GSCs). To study the mechanisms of GSCs resistance to radiation, two GSC lines, named line #1 and line #83, with different metabolic patterns and clinical outcome, were irradiated with photon beams and carbon ions and assessed by 1H Magnetic Resonance Spectroscopy (MRS). Both irradiation modalities induced early cytotoxic effects in line #1 with small effects on cell cycle, whereas a proliferative G2/M cytostatic block was observed in line #83. MR spectroscopy signals from mobile lipids (ML) increased in spectra of line #1 after photon and C-ion irradiation with effects on lipid unsaturation level, whereas no effects were detected in line #83 spectra. Gamma-Aminobutyric Acid (GABA), glutamic acid (glu) and Phosphocreatine (pCr) signals showed a significant variation only for line #1 after carbon ion irradiation. Glucose (glc) level and lactate (Lac) extrusion behaved differently in the two lines. Our findings suggest that the differences in irradiation response of GSCs #1 and #83 lines are likely attributable to their different metabolic fingerprint rather than to the different radiation types.
Collapse
Affiliation(s)
- Alessandra Palma
- National Centre for Innovative Technologies in Public Health, Istituto Superiore di Sanità, 00161 Rome, Italy; (A.P.); (S.G.); (A.M.L.); (V.D.); (L.G.); (V.V.)
| | - Sveva Grande
- National Centre for Innovative Technologies in Public Health, Istituto Superiore di Sanità, 00161 Rome, Italy; (A.P.); (S.G.); (A.M.L.); (V.D.); (L.G.); (V.V.)
| | - Lucia Ricci-Vitiani
- Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, 00161 Rome, Italy; (L.R.-V.); (M.B.); (M.B.)
| | - Anna Maria Luciani
- National Centre for Innovative Technologies in Public Health, Istituto Superiore di Sanità, 00161 Rome, Italy; (A.P.); (S.G.); (A.M.L.); (V.D.); (L.G.); (V.V.)
| | - Mariachiara Buccarelli
- Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, 00161 Rome, Italy; (L.R.-V.); (M.B.); (M.B.)
| | - Mauro Biffoni
- Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, 00161 Rome, Italy; (L.R.-V.); (M.B.); (M.B.)
| | - Valentina Dini
- National Centre for Innovative Technologies in Public Health, Istituto Superiore di Sanità, 00161 Rome, Italy; (A.P.); (S.G.); (A.M.L.); (V.D.); (L.G.); (V.V.)
- Istituto Nazionale di Fisica Nucleare INFN Sez. di Roma, 00185 Rome, Italy
| | - Giuseppe A. P. Cirrone
- National Institute for Nuclear Physics, Laboratori Nazionali del Sud, INFN-LNS, 95123 Catania, Italy;
| | - Mario Ciocca
- Centro Nazionale di Adroterapia Oncologica (CNAO)-National Center for Oncological Hadrontherapy, 27100 Pavia, Italy;
| | - Laura Guidoni
- National Centre for Innovative Technologies in Public Health, Istituto Superiore di Sanità, 00161 Rome, Italy; (A.P.); (S.G.); (A.M.L.); (V.D.); (L.G.); (V.V.)
| | - Roberto Pallini
- Department of Neuroscience, Fondazione Policlinico Universitario A. Gemelli, Università Cattolica del Sacro Cuore, 00168 Rome, Italy;
| | - Vincenza Viti
- National Centre for Innovative Technologies in Public Health, Istituto Superiore di Sanità, 00161 Rome, Italy; (A.P.); (S.G.); (A.M.L.); (V.D.); (L.G.); (V.V.)
| | - Antonella Rosi
- National Centre for Innovative Technologies in Public Health, Istituto Superiore di Sanità, 00161 Rome, Italy; (A.P.); (S.G.); (A.M.L.); (V.D.); (L.G.); (V.V.)
- Correspondence: ; Tel.: +39-06-49903159
| |
Collapse
|
|
32
|
Abstract
PURPOSE OF REVIEW Glioblastoma (GBM) is the most common malignant primary brain tumor, and the available treatment options are limited. This article reviews the recent preclinical and clinical investigations that seek to expand the repertoire of effective medical and radiotherapy options for GBM. RECENT FINDINGS Recent phase III trials evaluating checkpoint inhibition did not result in significant survival benefit. Select vaccine strategies have yielded promising results in early phase clinical studies and warrant further validation. Various targeted therapies are being explored but have yet to see breakthrough results. In addition, novel radiotherapy approaches are in development to maximize safe dose delivery. A multitude of preclinical and clinical studies in GBM explore promising immunotherapies, targeted agents, and novel radiation modalities. Recent phase III trial failures have once more highlighted the profound tumor heterogeneity and diverse resistance mechanisms of glioblastoma. This calls for the development of biomarker-driven and personalized treatment approaches.
Collapse
Affiliation(s)
- Elisa K Liu
- New York University Grossman School of Medicine, New York, NY, USA
| | - Erik P Sulman
- Department of Radiation Oncology, New York University Grossman School of Medicine, New York, NY, USA.,Brain and Spine Tumor Center, Laura and Isaac Perlmutter Cancer Center at NYU Langone Health, 240 E. 38th Street, 19th floor, New York, NY, 10019, USA
| | - Patrick Y Wen
- Center for Neuro-Oncology, Dana-Farber Cancer Institute, Boston, MA, USA
| | - Sylvia C Kurz
- Brain and Spine Tumor Center, Laura and Isaac Perlmutter Cancer Center at NYU Langone Health, 240 E. 38th Street, 19th floor, New York, NY, 10019, USA. .,Department of Neurology, New York University Grossman School of Medicine, New York, NY, USA.
| |
Collapse
|
|
33
|
A New Treatment Opportunity for DIPG and Diffuse Midline Gliomas: 5-ALA Augmented Irradiation, the 5aai Regimen. Brain Sci 2020; 10:brainsci10010051. [PMID: 31963414 PMCID: PMC7016657 DOI: 10.3390/brainsci10010051] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2019] [Revised: 01/14/2020] [Accepted: 01/16/2020] [Indexed: 12/19/2022] Open
Abstract
Prognosis for diffuse intrinsic pontine glioma (DIPG) and generally for diffuse midline gliomas (DMG) has only marginally improved over the last ~40 years despite dozens of chemotherapy and other therapeutic trials. The prognosis remains invariably fatal. We present here the rationale for a planned study of adding 5-aminolevulinic acid (5-ALA) to the current irradiation of DIPG or DMG: the 5aai regimen. In a series of recent papers, oral 5-ALA was shown to enhance standard therapeutic ionizing irradiation. 5-ALA is currently used in glioblastoma surgery to enable demarcation of overt tumor margins by virtue of selective uptake of 5-ALA by neoplastic cells and selective conversion to protoporphyrin IX (PpIX), which fluoresces after excitation by 410 nm (blue) light. 5-ALA is also useful in treating glioblastomas by virtue of PpIX's transfer of energy to O2 molecules, producing a singlet oxygen that in turn oxidizes intracellular DNA, lipids, and proteins, resulting in selective malignant cell cytotoxicity. This is called photodynamic treatment (PDT). Shallow penetration of light required for PpIX excitation and resultant energy transfer to O2 and cytotoxicity results in the inaccessibility of central structures like the pons or thalamus to sufficient light. The recent demonstration that keV and MeV photons can also excite PpIX and generate singlet O2 allows for reconsideration of 5-ALA PDT for treating DMG and DIPG. 5-ALA has an eminently benign side effect profile in adults and children. A pilot study in DIPG/DMG of slow uptitration of 5-ALA prior to each standard irradiation session-the 5aai regimen-is warranted.
Collapse
|