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Zhou S, Zhai W, Zhang Q, Li H, Fan Y. Impact of prophylactic cranial irradiation on survival in extensive-stage small cell lung cancer receiving first-line chemoimmunotherapy: a propensity score-matched study. Ther Adv Med Oncol 2025; 17:17588359251341158. [PMID: 40415872 PMCID: PMC12102569 DOI: 10.1177/17588359251341158] [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: 02/05/2025] [Accepted: 04/23/2025] [Indexed: 05/27/2025] Open
Abstract
Background Chemoimmunotherapy has emerged as the standard first-line treatment for extensive-stage small cell lung cancer (ES-SCLC), improving survival outcomes. However, the role of prophylactic cranial irradiation (PCI) in the context of chemoimmunotherapy remains undefined. Objectives This study aimed to evaluate the impact of PCI on overall survival (OS) in patients with ES-SCLC after chemoimmunotherapy administration. Design Retrospective study. Methods This retrospective analysis included 261 patients with ES-SCLC treated with first-line chemoimmunotherapy between January 2019 and December 2023. All patients underwent MRI scans to confirm the absence of brain metastases. After 1:2 propensity score matching (PSM), 46 and 81 patients were assigned to the PCI and observation groups, respectively. The primary endpoint was OS, with additional exploration of progression-free survival (PFS), the cumulative incidence of intracranial metastases, and intracranial progression-free survival (iPFS). Results After PSM, the two groups were well-balanced in baseline characteristics. Survival analysis showed a median OS of 19.9 months (95% confidence interval (CI): 11.8-28.0) in the PCI group and 15.6 months (12.3-18.9) in the observation group, without a significant difference (hazard ratio (HR) = 0.763 (95% CI: 0.484-1.206), log-rank p = 0.265). PCI significantly reduced the risk of brain metastasis (Fine-Gray p = 0.002), with 1-year cumulative incidence rates of 13.8% (3.4%-24.2%) in the PCI group and 53.4% (41.3%-65.6%) in the observation group. Subgroup analysis showed that for ES-SCLC patients achieving a partial response to initial chemoimmunotherapy, the PCI group had longer median OS (25.7 months (95% CI: 15.4-36.1) vs 19.4 months (15.4-23.4); HR = 0.502 (0.284-0.886); log-rank p = 0.021). Conclusion PCI did not improve OS in ES-SCLC patients receiving first-line chemoimmunotherapy, while it may confer a survival benefit for patients who achieve remission following chemoimmunotherapy. In addition, PCI significantly reduced the incidence of brain metastases. These findings warrant further randomized studies for verification.
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Affiliation(s)
- Shichao Zhou
- Department of Thoracic Medical Oncology, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine, Chinese Academy of Sciences, Hangzhou, Zhejiang, China
| | - Wanchen Zhai
- Department of Thoracic Medical Oncology, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine, Chinese Academy of Sciences, Hangzhou, Zhejiang, China
- Department of Oncology, The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Qian Zhang
- Department of Thoracic Medical Oncology, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine, Chinese Academy of Sciences, Hangzhou, Zhejiang, China
- Department of Oncology, The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Hui Li
- Department of Thoracic Medical Oncology, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine, Chinese Academy of Sciences, No. 1 East Banshan Road, Gongshu District, Hangzhou, Zhejiang 310022, China
| | - Yun Fan
- Department of Thoracic Medical Oncology, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine, Chinese Academy of Sciences, No. 1 East Banshan Road, Gongshu District, Hangzhou, Zhejiang 310022, China
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Ma Y, Ma X, Li C, Jiang Y, Zhang Z, Xiao J, Tian Y, Deng L, Zhang T, Wang J, Zhou Z, Li Y, Yi J, Chen X, Bi N. Personalized auto-segmentation for magnetic resonance imaging-guided adaptive radiotherapy of large brain metastases. Radiother Oncol 2025; 205:110773. [PMID: 39914742 DOI: 10.1016/j.radonc.2025.110773] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2024] [Revised: 01/26/2025] [Accepted: 01/29/2025] [Indexed: 02/12/2025]
Abstract
BACKGROUND AND PURPOSE Magnetic resonance-guided adaptive radiotherapy (MRgART) may improve the efficacy of large brain metastases (BMs)(≥2 cm), whereas the workflow requires optimized. This study develops a two-stage, personalized deep learning auto-segmentation (DLAS) model to assist online delineation of large BMs. MATERIALS AND METHODS Multi-sequences images from 177 BMs were trained to develop the basic DLAS model. Then, 741 daily online MR images of 20 large BMs from a prospective trial were collected for developing a personalized model. The dice similarity coefficient (DSC) was evaluated across three methods: basic model, rigid registration and personalized model, at intervals of every five fractions. The accuracy and efficiency were compared between manual delineation (MD) and DLAS assistant delineation (DLAS-AD) in 8 patients who underwent contrast T1 re-scan during MRgART. RESULTS The personalized DLAS model demonstrated significantly better performance compared to the basic model and rigid registration during the last fraction of MRgART (when the tumor volume achieved a significant reduction). The mean DSC for basic model vs. rigid registration vs. personalized model were 0.86 (p = 0.01) vs. 0.88 (p = 0.05) vs. 0.90, respectively. The DLAS-AD significantly improved contouring accuracy compared to MD, with a mean DSC of 0.89 vs. 0.85 (p = 0.001), and reduced contouring time by an average of 53.5 % (193 s vs. 424 s, p < 0.001). CONCLUSION Personalized DLAS model may increase the accuracy and efficiency of MD to optimize the workflow of MRgART for large BMs.
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Affiliation(s)
- Yuchao Ma
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China
| | - Xiangyu Ma
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China
| | - Canjun Li
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China
| | - Ying Jiang
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China
| | - Zhihui Zhang
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China
| | - Jianping Xiao
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China
| | - Yuan Tian
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China
| | - Lei Deng
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China
| | - Tao Zhang
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China
| | - Jianyang Wang
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China
| | - Zongmei Zhou
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China
| | - Yitong Li
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China
| | - Junlin Yi
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China.
| | - Xinyuan Chen
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China.
| | - Nan Bi
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China.
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Li Y, Liu F, Cai Q, Deng L, Ouyang Q, Zhang XHF, Zheng J. Invasion and metastasis in cancer: molecular insights and therapeutic targets. Signal Transduct Target Ther 2025; 10:57. [PMID: 39979279 PMCID: PMC11842613 DOI: 10.1038/s41392-025-02148-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2024] [Revised: 12/24/2024] [Accepted: 01/16/2025] [Indexed: 02/22/2025] Open
Abstract
The progression of malignant tumors leads to the development of secondary tumors in various organs, including bones, the brain, liver, and lungs. This metastatic process severely impacts the prognosis of patients, significantly affecting their quality of life and survival rates. Research efforts have consistently focused on the intricate mechanisms underlying this process and the corresponding clinical management strategies. Consequently, a comprehensive understanding of the biological foundations of tumor metastasis, identification of pivotal signaling pathways, and systematic evaluation of existing and emerging therapeutic strategies are paramount to enhancing the overall diagnostic and treatment capabilities for metastatic tumors. However, current research is primarily focused on metastasis within specific cancer types, leaving significant gaps in our understanding of the complex metastatic cascade, organ-specific tropism mechanisms, and the development of targeted treatments. In this study, we examine the sequential processes of tumor metastasis, elucidate the underlying mechanisms driving organ-tropic metastasis, and systematically analyze therapeutic strategies for metastatic tumors, including those tailored to specific organ involvement. Subsequently, we synthesize the most recent advances in emerging therapeutic technologies for tumor metastasis and analyze the challenges and opportunities encountered in clinical research pertaining to bone metastasis. Our objective is to offer insights that can inform future research and clinical practice in this crucial field.
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Affiliation(s)
- Yongxing Li
- Department of Urology, Urologic Surgery Center, Xinqiao Hospital, Third Military Medical University (Army Medical University), Chongqing, China
- State Key Laboratory of Trauma and Chemical Poisoning, Third Military Medical University (Army Medical University), Chongqing, China
| | - Fengshuo Liu
- Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, USA
- Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX, USA
- Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA
- McNair Medical Institute, Baylor College of Medicine, Houston, TX, USA
- Graduate School of Biomedical Science, Cancer and Cell Biology Program, Baylor College of Medicine, Houston, TX, USA
| | - Qingjin Cai
- Department of Urology, Urologic Surgery Center, Xinqiao Hospital, Third Military Medical University (Army Medical University), Chongqing, China
- State Key Laboratory of Trauma and Chemical Poisoning, Third Military Medical University (Army Medical University), Chongqing, China
| | - Lijun Deng
- Department of Medicinal Chemistry, Third Military Medical University (Army Medical University), Chongqing, China
| | - Qin Ouyang
- Department of Medicinal Chemistry, Third Military Medical University (Army Medical University), Chongqing, China.
| | - Xiang H-F Zhang
- Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, USA.
- Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX, USA.
- Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA.
- McNair Medical Institute, Baylor College of Medicine, Houston, TX, USA.
| | - Ji Zheng
- Department of Urology, Urologic Surgery Center, Xinqiao Hospital, Third Military Medical University (Army Medical University), Chongqing, China.
- State Key Laboratory of Trauma and Chemical Poisoning, Third Military Medical University (Army Medical University), Chongqing, China.
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Wald T, Hamm B, Holzschuh JC, El Shafie R, Kudak A, Kovacs B, Pflüger I, von Nettelbladt B, Ulrich C, Baumgartner MA, Vollmuth P, Debus J, Maier-Hein KH, Welzel T. Enhancing deep learning methods for brain metastasis detection through cross-technique annotations on SPACE MRI. Eur Radiol Exp 2025; 9:15. [PMID: 39913077 PMCID: PMC11802942 DOI: 10.1186/s41747-025-00554-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2024] [Accepted: 01/15/2025] [Indexed: 02/07/2025] Open
Abstract
BACKGROUND Gadolinium-enhanced "sampling perfection with application-optimized contrasts using different flip angle evolution" (SPACE) sequence allows better visualization of brain metastases (BMs) compared to "magnetization-prepared rapid acquisition gradient echo" (MPRAGE). We hypothesize that this better conspicuity leads to high-quality annotation (HAQ), enhancing deep learning (DL) algorithm detection of BMs on MPRAGE images. METHODS Retrospective contrast-enhanced (gadobutrol 0.1 mmol/kg) SPACE and MPRAGE data of 157 patients with BM were used, either annotated on MPRAGE resulting in normal annotation quality (NAQ) or on coregistered SPACE resulting in HAQ. Multiple DL methods were developed with NAQ or HAQ using either SPACE or MRPAGE images and evaluated on their detection performance using positive predictive value (PPV), sensitivity, and F1 score and on their delineation performance using volumetric Dice similarity coefficient, PPV, and sensitivity on one internal and four additional test datasets (660 patients). RESULTS The SPACE-HAQ model reached 0.978 PPV, 0.882 sensitivity, and 0.916 F1-score. The MPRAGE-HAQ reached 0.867, 0.839, and 0.840, the MPRAGE NAQ 0.964, 0.667, and 0.798, respectively (p ≥ 0.157). Relative to MPRAGE-NAQ, the MPRAGE-HAQ F1-score detection increased on all additional test datasets by 2.5-9.6 points (p < 0.016) and sensitivity improved on three datasets by 4.6-8.5 points (p < 0.001). Moreover, volumetric instance sensitivity improved by 3.6-7.6 points (p < 0.001). CONCLUSION HAQ improves DL methods without specialized imaging during application time. HAQ alone achieves about 40% of the performance improvements seen with SPACE images as input, allowing for fast and accurate, fully automated detection of small (< 1 cm) BMs. RELEVANCE STATEMENT Training with higher-quality annotations, created using the SPACE sequence, improves the detection and delineation sensitivity of DL methods for the detection of brain metastases (BMs)on MPRAGE images. This MRI cross-technique transfer learning is a promising way to increase diagnostic performance. KEY POINTS Delineating small BMs on SPACE MRI sequence results in higher quality annotations than on MPRAGE sequence due to enhanced conspicuity. Leveraging cross-technique ground truth annotations during training improved the accuracy of DL models in detecting and segmenting BMs. Cross-technique annotation may enhance DL models by integrating benefits from specialized, time-intensive MRI sequences while not relying on them. Further validation in prospective studies is needed.
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Affiliation(s)
- Tassilo Wald
- German Cancer Research Center (DKFZ) Heidelberg, Division of Medical Image Computing, Heidelberg, Germany.
- Helmholtz Imaging, German Cancer Research Center (DKFZ), Heidelberg, Germany.
- Faculty of Mathematics and Computer Science, Heidelberg University, Heidelberg, Germany.
| | - Benjamin Hamm
- German Cancer Research Center (DKFZ) Heidelberg, Division of Medical Image Computing, Heidelberg, Germany
- Medical Faculty Heidelberg, University of Heidelberg, Heidelberg, Germany
| | - Julius C Holzschuh
- Division of Radiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Rami El Shafie
- Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany
- Department of Radiation Oncology, University Hospital Göttingen, Göttingen, Germany
| | - Andreas Kudak
- Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany
- Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg, Germany
- Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Balint Kovacs
- German Cancer Research Center (DKFZ) Heidelberg, Division of Medical Image Computing, Heidelberg, Germany
- Medical Faculty Heidelberg, University of Heidelberg, Heidelberg, Germany
| | - Irada Pflüger
- Department of Neuroradiology, Heidelberg University Hospital, Heidelberg, Germany
- Division for Computational Neuroimaging, Heidelberg University Hospital, Heidelberg, Germany
| | - Bastian von Nettelbladt
- Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany
- Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg, Germany
- National Center for Tumor Diseases (NCT), NCT Heidelberg, a partnership between DKFZ and Heidelberg University Medical Center, Heidelberg, Germany
- German Cancer Consortium (DKTK), partner site Heidelberg, Heidelberg, Germany
- Heidelberg Ion-Beam Therapy Center (HIT), Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany
| | - Constantin Ulrich
- German Cancer Research Center (DKFZ) Heidelberg, Division of Medical Image Computing, Heidelberg, Germany
- Medical Faculty Heidelberg, University of Heidelberg, Heidelberg, Germany
- National Center for Tumor Diseases (NCT), NCT Heidelberg, a partnership between DKFZ and Heidelberg University Medical Center, Heidelberg, Germany
| | - Michael Anton Baumgartner
- German Cancer Research Center (DKFZ) Heidelberg, Division of Medical Image Computing, Heidelberg, Germany
- Helmholtz Imaging, German Cancer Research Center (DKFZ), Heidelberg, Germany
- Faculty of Mathematics and Computer Science, Heidelberg University, Heidelberg, Germany
| | - Philipp Vollmuth
- Department of Neuroradiology, Heidelberg University Hospital, Heidelberg, Germany
- Division for Computational Neuroimaging, Heidelberg University Hospital, Heidelberg, Germany
- Division for Computational Radiology Clinical AI (CCIBonn.ai), Clinic for Neuroradiology, University Hospital Bonn, Bonn, Germany
- Medical Faculty Bonn, University of Bonn, Bonn, Germany
| | - Jürgen Debus
- Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany
- Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg, Germany
- Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany
- National Center for Tumor Diseases (NCT), NCT Heidelberg, a partnership between DKFZ and Heidelberg University Medical Center, Heidelberg, Germany
- German Cancer Consortium (DKTK), partner site Heidelberg, Heidelberg, Germany
- Heidelberg Ion-Beam Therapy Center (HIT), Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany
| | - Klaus H Maier-Hein
- German Cancer Research Center (DKFZ) Heidelberg, Division of Medical Image Computing, Heidelberg, Germany
- Helmholtz Imaging, German Cancer Research Center (DKFZ), Heidelberg, Germany
- Faculty of Mathematics and Computer Science, Heidelberg University, Heidelberg, Germany
- National Center for Tumor Diseases (NCT), NCT Heidelberg, a partnership between DKFZ and Heidelberg University Medical Center, Heidelberg, Germany
- Pattern Analysis and Learning Group, Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany
- Translational Lung Research Center Heidelberg (TLRC), Member of the German Center for Lung Research (DZL), Heidelberg, Germany
| | - Thomas Welzel
- Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany
- Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg, Germany
- National Center for Tumor Diseases (NCT), NCT Heidelberg, a partnership between DKFZ and Heidelberg University Medical Center, Heidelberg, Germany
- German Cancer Consortium (DKTK), partner site Heidelberg, Heidelberg, Germany
- Heidelberg Ion-Beam Therapy Center (HIT), Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany
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Liulu X, Balaji P, Barber J, De Silva K, Murray T, Hickey A, Campbell T, Harris J, Gee H, Ahern V, Kumar S, Hau E, Qian PC. Radiation therapy for ventricular arrhythmias. J Med Imaging Radiat Oncol 2024; 68:893-913. [PMID: 38698577 PMCID: PMC11686466 DOI: 10.1111/1754-9485.13662] [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: 01/02/2024] [Accepted: 04/15/2024] [Indexed: 05/05/2024]
Abstract
Ventricular arrhythmias (VA) can be life-threatening arrhythmias that result in significant morbidity and mortality. Catheter ablation (CA) is an invasive treatment modality that can be effective in the treatment of VA where medications fail. Recurrence occurs commonly following CA due to an inability to deliver lesions of adequate depth to cauterise the electrical circuits that drive VA or reach areas of scar responsible for VA. Stereotactic body radiotherapy is a non-invasive treatment modality that allows volumetric delivery of energy to treat circuits that cannot be reached by CA. It overcomes the weaknesses of CA and has been successfully utilised in small clinical trials to treat refractory VA. This article summarises the current evidence for this novel treatment modality and the steps that will be required to bring it to the forefront of VA treatment.
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Affiliation(s)
- Xingzhou Liulu
- Cardiology DepartmentRoyal North Shore HospitalSydneyNew South WalesAustralia
| | - Poornima Balaji
- Cardiology Department, Westmead HospitalUniversity of SydneySydneyNew South WalesAustralia
- Westmead Applied Research Centre, Faculty of Medicine and HealthUniversity of SydneySydneyNew South WalesAustralia
| | - Jeffrey Barber
- Department of Radiation Oncology, Crown Princess Mary Cancer CentreWestmead HospitalSydneyNew South WalesAustralia
- Sydney Medical School, University of SydneySydneyNew South WalesAustralia
| | - Kasun De Silva
- Cardiology Department, Westmead HospitalUniversity of SydneySydneyNew South WalesAustralia
- Westmead Applied Research Centre, Faculty of Medicine and HealthUniversity of SydneySydneyNew South WalesAustralia
| | - Tiarne Murray
- Department of Radiation Oncology, Crown Princess Mary Cancer CentreWestmead HospitalSydneyNew South WalesAustralia
| | - Andrew Hickey
- Department of Radiation Oncology, Crown Princess Mary Cancer CentreWestmead HospitalSydneyNew South WalesAustralia
| | - Timothy Campbell
- Cardiology Department, Westmead HospitalUniversity of SydneySydneyNew South WalesAustralia
- Westmead Applied Research Centre, Faculty of Medicine and HealthUniversity of SydneySydneyNew South WalesAustralia
| | - Jill Harris
- Department of Radiation Oncology, Crown Princess Mary Cancer CentreWestmead HospitalSydneyNew South WalesAustralia
| | - Harriet Gee
- Department of Radiation Oncology, Crown Princess Mary Cancer CentreWestmead HospitalSydneyNew South WalesAustralia
- Sydney Medical School, University of SydneySydneyNew South WalesAustralia
| | - Verity Ahern
- Department of Radiation Oncology, Crown Princess Mary Cancer CentreWestmead HospitalSydneyNew South WalesAustralia
- Sydney Medical School, University of SydneySydneyNew South WalesAustralia
| | - Saurabh Kumar
- Cardiology Department, Westmead HospitalUniversity of SydneySydneyNew South WalesAustralia
- Westmead Applied Research Centre, Faculty of Medicine and HealthUniversity of SydneySydneyNew South WalesAustralia
- Sydney Medical School, University of SydneySydneyNew South WalesAustralia
| | - Eric Hau
- Department of Radiation Oncology, Crown Princess Mary Cancer CentreWestmead HospitalSydneyNew South WalesAustralia
- Sydney Medical School, University of SydneySydneyNew South WalesAustralia
- Translational Radiation Biology and Oncology Laboratory, Centre for Cancer ResearchThe Westmead Institute for Medical ResearchSydneyNew South WalesAustralia
- Blacktown Hematology and Cancer Centre, Blacktown HospitalBlacktownNew South WalesAustralia
| | - Pierre C Qian
- Cardiology Department, Westmead HospitalUniversity of SydneySydneyNew South WalesAustralia
- Westmead Applied Research Centre, Faculty of Medicine and HealthUniversity of SydneySydneyNew South WalesAustralia
- Sydney Medical School, University of SydneySydneyNew South WalesAustralia
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Chun SJ, Kim K, Kim YB, Paek SH, Lee KH, Song JH, Jang WI, Kim TH, Salvestrini V, Meattini I, Livi L, Shin KH. Risk of radionecrosis in HER2-positive breast cancer with brain metastasis receiving trastuzumab emtansine (T-DM1) and brain stereotactic radiosurgery. Radiother Oncol 2024; 199:110461. [PMID: 39067706 DOI: 10.1016/j.radonc.2024.110461] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2024] [Revised: 07/18/2024] [Accepted: 07/22/2024] [Indexed: 07/30/2024]
Abstract
OBJECTIVES To investigate the potential relationship between trastuzumab emtansine (T-DM1) treatment and radionecrosis induced by brain stereotactic radiosurgery (SRS) in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer. MATERIALS AND METHODS Patients with HER2-positive breast cancer who were diagnosed with brain metastasis and received both SRS and HER2-targeted agents between 2012 and 2022 were retrospectively analyzed. Patients who received T-DM1 within 1 year (either before or after) of SRS were considered as 'T-DM1 exposure (+)'. T-DM1 exposure (-) group had other HER2-targeted agents or received T-DM1 more than 1 year before or after SRS. Symptomatic radionecrosis was defined as Common Terminology Criteria for Adverse Events grade 2 or greater. RESULTS A total of 103 patients with 535 treatment sessions were included from seven tertiary medical centers in Korea and Italy. The median follow-up duration was 15.5 months (range 1.1-101.9). By per-patient analysis, T-DM1 exposure (+) group had an increased risk of overall radionecrosis after multivariate analysis (HR 2.71, p = 0.020). Additionally, T-DM1 exposure (+) group was associated with a higher risk of symptomatic radionecrosis compared to T-DM1 exposure (-) patients (HR 4.34, p = 0.030). In per-treatment analysis, T-DM1 exposure (+) was linked to higher incidences of overall (HR 3.13, p = 0.036) and symptomatic radionecrosis (HR 10.4, p = 0.013) after multivariate analysis. A higher prevalence of radionecrosis was observed with T-DM1 exposure (+) and a previous history of whole brain radiotherapy. CONCLUSION An increased risk of radionecrosis was observed in patients receiving T-DM1 with brain SRS. Further research is needed to better understand the optimal sequence and interval for administering T-DM1 and SRS.
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Affiliation(s)
- Seok-Joo Chun
- Department of Radiation Oncology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea; Department of Radiation Oncology, Dongguk University Ilsan Hospital, Dongguk University College of Medicine, Goyang, South Korea
| | - Kyubo Kim
- Department of Radiation Oncology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, South Korea.
| | - Yong Bae Kim
- Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea
| | - Sun Ha Paek
- Department of Neurosurgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea
| | - Kyung-Hun Lee
- Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea
| | - Jin-Ho Song
- Department of Radiation Oncology, Seoul St. Mary's Hospital, The Catholic University of Korea College of Medicine, Seoul, South Korea
| | - Won Il Jang
- Department of Radiation Oncology, Korea Institute of Radiological & Medical Sciences, Seoul, South Korea
| | - Tae Hyun Kim
- Center for Proton Therapy, National Cancer Center, Goyang, South Korea
| | - Viola Salvestrini
- Breast Unit & Radiation Oncology Unit, Oncology Department, Azienda Ospedaliero Universitaria Careggi, Florence, Italy
| | - Icro Meattini
- Breast Unit & Radiation Oncology Unit, Oncology Department, Azienda Ospedaliero Universitaria Careggi, Florence, Italy; Department of Experimental and Clinical Biomedical Sciences "M. Serio", University of Florence, Florence, Italy
| | - Lorenzo Livi
- Breast Unit & Radiation Oncology Unit, Oncology Department, Azienda Ospedaliero Universitaria Careggi, Florence, Italy; Department of Experimental and Clinical Biomedical Sciences "M. Serio", University of Florence, Florence, Italy
| | - Kyung Hwan Shin
- Department of Radiation Oncology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea.
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Chen PJ, Lin HL. Severe pneumocranium after gamma knife stereotactic radiosurgery for brain metastasis: A case report and literature review. Medicine (Baltimore) 2024; 103:e38464. [PMID: 38847695 PMCID: PMC11155530 DOI: 10.1097/md.0000000000038464] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2024] [Accepted: 05/15/2024] [Indexed: 06/10/2024] Open
Abstract
RATIONALE Gamma knife stereotactic radiosurgery (GKRS) is a recognized safe and effective treatment for brain metastasis; however, some complications can present significant clinical challenges. This case report highlights a rare occurrence of cerebrospinal fluid (CSF) leakage and pneumocranium following GKRS, emphasizing the need for awareness and prompt management of these complications. PATIENT CONCERNS A 35-year-old male with a history of malignant neoplasm of the lip in 2015 and perineural spread of malignancy into the left cavernous sinus was treated with GKRS in 2017. The patient was admitted emergently 39 days after discharge due to persistent headache and dizziness. DIAGNOSES Brain computed tomography (CT) revealed diffuse bilateral pneumocranium alongside an observation of CSF leakage. INTERVENTIONS A surgical procedure involving a left frontal-temporal craniotomy was performed to excise a residual skull base tumor and repair the dura, guided by a navigator system. The conclusive pathological assessment revealed the presence of squamous cell carcinoma markers. OUTCOMES The patient exhibited excellent tolerance to the entire procedure and experienced a prompt and uneventful recovery process. After surgery, the symptoms alleviated and CSF leak stopped. The follow-up image showed the pneumocranium resolved. LESSONS Pneumocranium due to early-stage post-GKRS is uncommon. The rapid tumor shrinkage and timing of brain metastasis spreading through the dura can lead to CSF leak and pneumocranium. We reviewed current treatment options and presented a successful craniotomy-based dura repair case.
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Affiliation(s)
- Paul J. Chen
- Department of Neurosurgery, China Medical University Hospital, Taichung City, Taiwan (R.O.C.)
| | - Hung-Lin Lin
- Department of Neurosurgery, China Medical University Hospital, Taichung City, Taiwan (R.O.C.)
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Salans M, Ni L, Morin O, Ziemer B, Capaldi DPI, Raleigh DR, Vasudevan HN, Chew J, Nakamura J, Sneed PK, Boreta L, Villanueva-Meyer JE, Theodosopoulos P, Braunstein S. Adverse radiation effect versus tumor progression following stereotactic radiosurgery for brain metastases: Implications of radiologic uncertainty. J Neurooncol 2024; 166:535-546. [PMID: 38316705 PMCID: PMC10876820 DOI: 10.1007/s11060-024-04578-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2023] [Accepted: 01/17/2024] [Indexed: 02/07/2024]
Abstract
BACKGROUND Adverse radiation effect (ARE) following stereotactic radiosurgery (SRS) for brain metastases is challenging to distinguish from tumor progression. This study characterizes the clinical implications of radiologic uncertainty (RU). METHODS Cases reviewed retrospectively at a single-institutional, multi-disciplinary SRS Tumor Board between 2015-2022 for RU following SRS were identified. Treatment history, diagnostic or therapeutic interventions performed upon RU resolution, and development of neurologic deficits surrounding intervention were obtained from the medical record. Differences in lesion volume and maximum diameter at RU onset versus resolution were compared with paired t-tests. Median time from RU onset to resolution was estimated using the Kaplan-Meier method. Univariate and multivariate associations between clinical characteristics and time to RU resolution were assessed with Cox proportional-hazards regression. RESULTS Among 128 lesions with RU, 23.5% had undergone ≥ 2 courses of radiation. Median maximum diameter (20 vs. 16 mm, p < 0.001) and volume (2.7 vs. 1.5 cc, p < 0.001) were larger upon RU resolution versus onset. RU resolution took > 6 and > 12 months in 25% and 7% of cases, respectively. Higher total EQD2 prior to RU onset (HR = 0.45, p = 0.03) and use of MR perfusion (HR = 0.56, p = 0.001) correlated with shorter time to resolution; larger volume (HR = 1.05, p = 0.006) portended longer time to resolution. Most lesions (57%) were diagnosed as ARE. Most patients (58%) underwent an intervention upon RU resolution; of these, 38% developed a neurologic deficit surrounding intervention. CONCLUSIONS RU resolution took > 6 months in > 25% of cases. RU may lead to suboptimal outcomes and symptom burden. Improved characterization of post-SRS RU is needed.
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Affiliation(s)
- Mia Salans
- Department of Radiation Oncology, University of California San Francisco (MS, LN, OM, BZ, DPIC, DRR, HNV, JC, JN, PKS, LB, SB), 505 Parnassus Ave, L75, San Francisco, CA, 94158, USA
| | - Lisa Ni
- Department of Radiation Oncology, University of California San Francisco (MS, LN, OM, BZ, DPIC, DRR, HNV, JC, JN, PKS, LB, SB), 505 Parnassus Ave, L75, San Francisco, CA, 94158, USA
| | - Olivier Morin
- Department of Radiation Oncology, University of California San Francisco (MS, LN, OM, BZ, DPIC, DRR, HNV, JC, JN, PKS, LB, SB), 505 Parnassus Ave, L75, San Francisco, CA, 94158, USA
| | - Benjamin Ziemer
- Department of Radiation Oncology, University of California San Francisco (MS, LN, OM, BZ, DPIC, DRR, HNV, JC, JN, PKS, LB, SB), 505 Parnassus Ave, L75, San Francisco, CA, 94158, USA
| | - Dante P I Capaldi
- Department of Radiation Oncology, University of California San Francisco (MS, LN, OM, BZ, DPIC, DRR, HNV, JC, JN, PKS, LB, SB), 505 Parnassus Ave, L75, San Francisco, CA, 94158, USA
| | - David R Raleigh
- Department of Radiation Oncology, University of California San Francisco (MS, LN, OM, BZ, DPIC, DRR, HNV, JC, JN, PKS, LB, SB), 505 Parnassus Ave, L75, San Francisco, CA, 94158, USA
- Department of Neurosurgery, University of California San Francisco (DRR, JEVM, PT), San Francisco, USA
- Department of Pathology, University of California San Francisco (DRR), San Francisco, USA
| | - Harish N Vasudevan
- Department of Radiation Oncology, University of California San Francisco (MS, LN, OM, BZ, DPIC, DRR, HNV, JC, JN, PKS, LB, SB), 505 Parnassus Ave, L75, San Francisco, CA, 94158, USA
- Department of Neurosurgery, University of California San Francisco (DRR, JEVM, PT), San Francisco, USA
| | - Jessica Chew
- Department of Radiation Oncology, University of California San Francisco (MS, LN, OM, BZ, DPIC, DRR, HNV, JC, JN, PKS, LB, SB), 505 Parnassus Ave, L75, San Francisco, CA, 94158, USA
| | - Jean Nakamura
- Department of Radiation Oncology, University of California San Francisco (MS, LN, OM, BZ, DPIC, DRR, HNV, JC, JN, PKS, LB, SB), 505 Parnassus Ave, L75, San Francisco, CA, 94158, USA
| | - Penny K Sneed
- Department of Radiation Oncology, University of California San Francisco (MS, LN, OM, BZ, DPIC, DRR, HNV, JC, JN, PKS, LB, SB), 505 Parnassus Ave, L75, San Francisco, CA, 94158, USA
| | - Lauren Boreta
- Department of Radiation Oncology, University of California San Francisco (MS, LN, OM, BZ, DPIC, DRR, HNV, JC, JN, PKS, LB, SB), 505 Parnassus Ave, L75, San Francisco, CA, 94158, USA
| | - Javier E Villanueva-Meyer
- Department of Neurosurgery, University of California San Francisco (DRR, JEVM, PT), San Francisco, USA
- Department of Radiology and Biomedical Imaging, University of California San Francisco (JEVM), San Francisco, USA
| | - Philip Theodosopoulos
- Department of Neurosurgery, University of California San Francisco (DRR, JEVM, PT), San Francisco, USA
| | - Steve Braunstein
- Department of Radiation Oncology, University of California San Francisco (MS, LN, OM, BZ, DPIC, DRR, HNV, JC, JN, PKS, LB, SB), 505 Parnassus Ave, L75, San Francisco, CA, 94158, USA.
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Dagher R, Gad M, da Silva de Santana P, Sadeghi MA, Yewedalsew SF, Gujar SK, Yedavalli V, Köhler CA, Khan M, Tavora DGF, Kamson DO, Sair HI, Luna LP. Umbrella review and network meta-analysis of diagnostic imaging test accuracy studies in Differentiating between brain tumor progression versus pseudoprogression and radionecrosis. J Neurooncol 2024; 166:1-15. [PMID: 38212574 DOI: 10.1007/s11060-023-04528-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2023] [Accepted: 12/01/2023] [Indexed: 01/13/2024]
Abstract
PURPOSE In this study we gathered and analyzed the available evidence regarding 17 different imaging modalities and performed network meta-analysis to find the most effective modality for the differentiation between brain tumor recurrence and post-treatment radiation effects. METHODS We conducted a comprehensive systematic search on PubMed and Embase. The quality of eligible studies was assessed using the Assessment of Multiple Systematic Reviews-2 (AMSTAR-2) instrument. For each meta-analysis, we recalculated the effect size, sensitivity, specificity, positive and negative likelihood ratios, and diagnostic odds ratio from the individual study data provided in the original meta-analysis using a random-effects model. Imaging technique comparisons were then assessed using NMA. Ranking was assessed using the multidimensional scaling approach and by visually assessing surface under the cumulative ranking curves. RESULTS We identified 32 eligible studies. High confidence in the results was found in only one of them, with a substantial heterogeneity and small study effect in 21% and 9% of included meta-analysis respectively. Comparisons between MRS Cho/NAA, Cho/Cr, DWI, and DSC were most studied. Our analysis showed MRS (Cho/NAA) and 18F-DOPA PET displayed the highest sensitivity and negative likelihood ratios. 18-FET PET was ranked highest among the 17 studied techniques with statistical significance. APT MRI was the only non-nuclear imaging modality to rank higher than DSC, with statistical insignificance, however. CONCLUSION The evidence regarding which imaging modality is best for the differentiation between radiation necrosis and post-treatment radiation effects is still inconclusive. Using NMA, our analysis ranked FET PET to be the best for such a task based on the available evidence. APT MRI showed promising results as a non-nuclear alternative.
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Affiliation(s)
- Richard Dagher
- Russell H. Morgan Department of Radiology and Radiological Science, Division of Neuroradiology, Johns Hopkins Hospital, 600 N Wolfe Street Phipps B100F, Baltimore, MD, 21287, USA
| | - Mona Gad
- Diagnostic Radiology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | | | - Mohammad Amin Sadeghi
- Russell H. Morgan Department of Radiology and Radiological Science, Division of Neuroradiology, Johns Hopkins Hospital, 600 N Wolfe Street Phipps B100F, Baltimore, MD, 21287, USA
| | | | - Sachin K Gujar
- Russell H. Morgan Department of Radiology and Radiological Science, Division of Neuroradiology, Johns Hopkins Hospital, 600 N Wolfe Street Phipps B100F, Baltimore, MD, 21287, USA
| | - Vivek Yedavalli
- Russell H. Morgan Department of Radiology and Radiological Science, Division of Neuroradiology, Johns Hopkins Hospital, 600 N Wolfe Street Phipps B100F, Baltimore, MD, 21287, USA
| | - Cristiano André Köhler
- Medical Sciences Post-Graduation Program, Department of Internal Medicine, School of Medicine, Federal University of Ceará, Fortaleza, Brazil
| | - Majid Khan
- Russell H. Morgan Department of Radiology and Radiological Science, Division of Neuroradiology, Johns Hopkins Hospital, 600 N Wolfe Street Phipps B100F, Baltimore, MD, 21287, USA
| | | | - David Olayinka Kamson
- The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD, USA
| | - Haris I Sair
- Russell H. Morgan Department of Radiology and Radiological Science, Division of Neuroradiology, Johns Hopkins Hospital, 600 N Wolfe Street Phipps B100F, Baltimore, MD, 21287, USA
| | - Licia P Luna
- Russell H. Morgan Department of Radiology and Radiological Science, Division of Neuroradiology, Johns Hopkins Hospital, 600 N Wolfe Street Phipps B100F, Baltimore, MD, 21287, USA.
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Anderson W, Ponce FA, Kinsman MJ, Sani S, Hwang B, Ghinda D, Kogan M, Mahoney JM, Amin DB, Van Horn M, McGuckin JP, Razo-Castaneda D, Bucklen BS. Robotic-Assisted Navigation for Stereotactic Neurosurgery: A Cadaveric Investigation of Accuracy, Time, and Radiation. Oper Neurosurg (Hagerstown) 2023; 26:01787389-990000000-00991. [PMID: 38054727 PMCID: PMC11008650 DOI: 10.1227/ons.0000000000001024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2023] [Accepted: 10/18/2023] [Indexed: 12/07/2023] Open
Abstract
BACKGROUND AND OBJECTIVES Despite frequent use, stereotactic head frames require manual coordinate calculations and manual frame settings that are associated with human error. This study examines freestanding robot-assisted navigation (RAN) as a means to reduce the drawbacks of traditional cranial stereotaxy and improve targeting accuracy. METHODS Seven cadaveric human torsos with heads were tested with 8 anatomic coordinates selected for lead placement mirrored in each hemisphere. Right and left hemispheres of the brain were randomly assigned to either the traditional stereotactic arc-based (ARC) group or the RAN group. Both target accuracy and trajectory accuracy were measured. Procedural time and the radiation required for registration were also measured. RESULTS The accuracy of the RAN group was significantly greater than that of the ARC group in both target (1.2 ± 0.5 mm vs 1.7 ± 1.2 mm, P = .005) and trajectory (0.9 ± 0.6 mm vs 1.3 ± 0.9 mm, P = .004) measurements. Total procedural time was also significantly faster for the RAN group than for the ARC group (44.6 ± 7.7 minutes vs 86.0 ± 12.5 minutes, P < .001). The RAN group had significantly reduced time per electrode placement (2.9 ± 0.9 minutes vs 5.8 ± 2.0 minutes, P < .001) and significantly reduced radiation during registration (1.9 ± 1.1 mGy vs 76.2 ± 5.0 mGy, P < .001) compared with the ARC group. CONCLUSION In this cadaveric study, cranial leads were placed faster and with greater accuracy using RAN than those placed with conventional stereotactic arc-based technique. RAN also required significantly less radiation to register the specimen's coordinate system to the planned trajectories. Clinical testing should be performed to further investigate RAN for stereotactic cranial surgery.
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Affiliation(s)
- William Anderson
- Department of Neurosurgery, The Johns Hopkins Hospital, Baltimore, Maryland, USA
| | - Francisco A. Ponce
- Department of Neurosurgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona, USA
| | - Michael J. Kinsman
- Neurosurgery, University of Kansas Medical Center, Kansas City, Kansas, USA
| | - Sepehr Sani
- Department of Neurosurgery, Rush University Medical Center, Chicago, Illinois, USA
| | - Brian Hwang
- Department of Neurosurgery, The Johns Hopkins Hospital, Baltimore, Maryland, USA
- Current Affiliation: Orange County Neurosurgical Associates, Laguna Hills, California, USA
| | - Diana Ghinda
- Department of Neurosurgery, The Johns Hopkins Hospital, Baltimore, Maryland, USA
| | - Michael Kogan
- Department of Neurological Surgery, Thomas Jefferson University Hospitals, Philadelphia, Pennsylvania, USA
| | - Jonathan M. Mahoney
- Musculoskeletal Education and Research Center, A Division of Globus Medical, Inc., Audubon, Pennsylvania, USA
| | - Dhara B. Amin
- Musculoskeletal Education and Research Center, A Division of Globus Medical, Inc., Audubon, Pennsylvania, USA
| | - Margaret Van Horn
- Musculoskeletal Education and Research Center, A Division of Globus Medical, Inc., Audubon, Pennsylvania, USA
| | - Joshua P. McGuckin
- Musculoskeletal Education and Research Center, A Division of Globus Medical, Inc., Audubon, Pennsylvania, USA
| | - Dominic Razo-Castaneda
- School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, Pennsylvania, USA
| | - Brandon S. Bucklen
- Musculoskeletal Education and Research Center, A Division of Globus Medical, Inc., Audubon, Pennsylvania, USA
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Roh YH, Park JE, Kang S, Yoon S, Kim SW, Kim HS. Prognostic value of MRI volumetric parameters in non-small cell lung cancer patients after immune checkpoint inhibitor therapy: comparison with response assessment criteria. Cancer Imaging 2023; 23:102. [PMID: 37875970 PMCID: PMC10594817 DOI: 10.1186/s40644-023-00624-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2023] [Accepted: 10/16/2023] [Indexed: 10/26/2023] Open
Abstract
BACKGROUND Accurate response parameters are important for patients with brain metastasis (BM) undergoing clinical trials using immunotherapy, considering poorly defined enhancement and variable responses. This study investigated MRI-based surrogate endpoints for patients with BM receiving immunotherapy. METHODS Sixty-three non-small cell lung cancer patients with BM who received immune checkpoint inhibitors and underwent MRI were included. Tumor diameters were measured using a modification of the RECIST 1.1 (mRECIST), RANO-BM, and iRANO adjusted for BM (iRANO-BM). Tumor volumes were segmented on 3D contrast-enhanced T1-weighted imaging. Differences between the sum of the longest diameter (SLD) or total tumor volume at baseline and the corresponding measurement at time of the best overall response were calculated as "changes in SLDs" (for each set of criteria) and "change in volumetry," respectively. Overall response rate (ORR), progressive disease (PD) assignment, and progression-free survival (PFS) were compared among the criteria. The prediction of overall survival (OS) was compared between diameter-based and volumetric change using Cox proportional hazards regression analysis. RESULTS The mRECIST showed higher ORR (30.1% vs. both 17.5%) and PD assignment (34.9% vs. 25.4% [RANO-BM] and 19% [iRANO-BM]). The iRANO-BM had a longer median PFS (13.7 months) than RANO-BM (9.53 months) and mRECIST (7.73 months, P = 0.003). The change in volumetry was a significant predictor of OS (HR = 5.87, 95% CI: 1.46-23.64, P = 0.013). None of the changes in SLDs, as determined by RANO-BM or iRANO-BM, were significant predictors of OS, except for the mRECIST, which exhibited a weak association with OS. CONCLUSION Quantitative volume measurement may be an accurate surrogate endpoint for OS in patients with BM undergoing immunotherapy, especially considering the challenges of multiplicity and the heterogeneity of sub-centimeter size responses.
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Affiliation(s)
- Yun Hwa Roh
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea
| | - Ji Eun Park
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea.
| | - Sora Kang
- Division of Hematology and Oncology, Department of Internal Medicine, Chungnam National University Hospital, Daejeon, Republic of Korea
| | - Shinkyo Yoon
- Department of Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Sang-We Kim
- Department of Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Ho Sung Kim
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea
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Mannam SS, Bray DP, Nwagwu CD, Zhong J, Shu HK, Eaton B, Sudmeier L, Goyal S, Deibert C, Nduom EK, Olson J, Hoang KB. Examining the Effect of ALK and EGFR Mutations on Survival Outcomes in Surgical Lung Brain Metastasis Patients. Cancers (Basel) 2023; 15:4773. [PMID: 37835467 PMCID: PMC10572022 DOI: 10.3390/cancers15194773] [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: 08/11/2023] [Revised: 09/24/2023] [Accepted: 09/28/2023] [Indexed: 10/15/2023] Open
Abstract
In the context of the post-genomic era, where targeted oncological therapies like monoclonal antibodies (mAbs) and tyrosine-kinase inhibitors (TKIs) are gaining prominence, this study investigates whether these therapies can enhance survival for lung carcinoma patients with specific genetic mutations-EGFR-amplified and ALK-rearranged mutations. Prior to this study, no research series had explored how these mutations influence patient survival in cases of surgical lung brain metastases (BMs). Through a multi-site retrospective analysis, the study examined patients who underwent surgical resection for BM arising from primary lung cancer at Emory University Hospital from January 2012 to May 2022. The mutational statuses were determined from brain tissue biopsies, and survival analyses were conducted. Results from 95 patients (average age: 65.8 ± 10.6) showed that while 6.3% had anaplastic lymphoma kinase (ALK)-rearranged mutations and 20.0% had epidermal growth factor receptor (EGFR)-amplified mutations-with 9.5% receiving second-line therapies-these mutations did not significantly correlate with overall survival. Although the sample size of patients receiving targeted therapies was limited, the study highlighted improved overall survival and progression-free survival rates compared to earlier trials, suggesting advancements in systemic lung metastasis treatment. The study suggests that as more targeted therapies emerge, the prospects for increased overall survival and progression-free survival in lung brain metastasis patients will likely improve.
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Affiliation(s)
- Sneha Sai Mannam
- Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
| | - David P. Bray
- Department of Neurosurgery, Jefferson University Hospital, Philadelphia, PA 19107, USA
| | - Chibueze D. Nwagwu
- Department of Neurosurgery, Brigham and Women’s Hospital, Boston, MA 02115, USA
| | - Jim Zhong
- Department of Radiation Oncology, Emory University School of Medicine, Atlanta, GA 30322, USA (H.-K.S.)
| | - Hui-Kuo Shu
- Department of Radiation Oncology, Emory University School of Medicine, Atlanta, GA 30322, USA (H.-K.S.)
| | - Bree Eaton
- Department of Radiation Oncology, Emory University School of Medicine, Atlanta, GA 30322, USA (H.-K.S.)
| | - Lisa Sudmeier
- Department of Radiation Oncology, Emory University School of Medicine, Atlanta, GA 30322, USA (H.-K.S.)
| | - Subir Goyal
- Biostatistics Shared Resource, Winship Cancer Institute, Emory University, Atlanta, GA 30322, USA
| | - Christopher Deibert
- Department of Neurosurgery, Emory University School of Medicine, Atlanta, GA 30322, USA
| | - Edjah K. Nduom
- Department of Neurosurgery, Emory University School of Medicine, Atlanta, GA 30322, USA
| | - Jeffrey Olson
- Department of Neurosurgery, Emory University School of Medicine, Atlanta, GA 30322, USA
| | - Kimberly B. Hoang
- Department of Neurosurgery, Emory University School of Medicine, Atlanta, GA 30322, USA
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Chen VE, Kim M, Nelson N, Kim IK, Shi W. Cost-effectiveness analysis of 3 radiation treatment strategies for patients with multiple brain metastases. Neurooncol Pract 2023; 10:344-351. [PMID: 37457226 PMCID: PMC10346394 DOI: 10.1093/nop/npac093] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2023] Open
Abstract
Background Patients diagnosed with multiple brain metastases often survive for less than 2 years, and clinicians must carefully evaluate the impact of interventions on quality of life. Three types of radiation treatment are widely accepted for patients with multiple brain metastases: Whole brain radiation therapy (WBRT), hippocampal avoidance whole-brain radiation therapy (HA-WBRT), and stereotactic radiosurgery (SRS). WBRT, the standard option, is less costly than its newer alternatives but causes more severe adverse effects such as memory loss. To determine whether the cost-effectiveness ratio of HA-WBRT and SRS are superior to WBRT, we used published data to simulate cases of multiple brain metastases. Methods We designed a Markov model using data from previously published studies to simulate the disease course of patients with 5 to 15 brain metastases and determine the cost-effectiveness of HA-WBRT and SRS relative to WBRT. Incremental cost-effectiveness ratios (ICERs) were calculated and compared against a willingness-to-pay threshold of $100 000 per quality-adjusted life year. Results SRS met the threshold for cost-effectiveness, with ICERs ranging $41 198-$54 852 for patients with 5 to 15 brain metastases; however, HA-WBRT was not cost-effective, with an ICER of $163 915 for all simulated patients. Model results were robust to sensitivity analyses. Conclusions We propose that SRS, but not HA-WBRT, should be offered to patients with multiple brain metastases as a treatment alternative to standard WBRT. Incorporating these findings into clinical practice will help promote patient-centered care and decrease national healthcare expenditures, thereby addressing issues around health equity and access to care.
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Affiliation(s)
- Victor Eric Chen
- Department of Radiation Oncology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
| | - Minchul Kim
- Center for Outcomes Research, University of Illinois College of Medicine at Peoria, Peoria, Illinois, USA
| | - Nicolas Nelson
- Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
| | - Inkyu Kevin Kim
- College of Population Health, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
| | - Wenyin Shi
- Department of Radiation Oncology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
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Ding S, Liu B, Zheng S, Wang D, Liu M, Liu H, Zhang P, Peng K, He H, Zhou R, Guo J, Qiu B, Huang X, Liu H. An exploratory analysis of MR-guided fractionated stereotactic radiotherapy in patients with brain metastases. Clin Transl Radiat Oncol 2023; 40:100602. [PMID: 36910023 PMCID: PMC9996243 DOI: 10.1016/j.ctro.2023.100602] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2022] [Revised: 02/15/2023] [Accepted: 02/19/2023] [Indexed: 02/24/2023] Open
Abstract
Purpose To assess the feasibility and potential benefits of online adaptive MR-guided fractionated stereotatic radiotherapy (FSRT) in patients with brain metastases (BMs). Methods and materials Twenty-eight consecutive patients with BMs were treated with FSRT of 30 Gy in 5 fractions on the 1.5 T MR-Linac. The FSRT fractions employed daily MR scans and the contours were utilized to create each adapted plan. The brain lesions and perilesional edema were delineated on MR images of pre-treatment simulation (Fx0) and all fractions (Fx1, Fx2, Fx3, Fx4 and Fx5) to evaluate the inter-fractional changes. These changes were quantified using absolute/relative volume, Dice similarity coefficient (DSC) and Hausdorff distance (HD) metrics. Planning target volume (PTV) coverage and organ at risk (OAR) constraints were used to compare non-adaptive and adaptive plans. Results A total of 28 patients with 88 lesions were evaluated, and 23 patients (23/28, 82.1%) had primary lung adenocarcinoma. Significant tumor volume reduction had been found during FSRT compared to Fx0 for all 88 lesions (median -0.75%, -5.33%, -9.32%, -17.96% and -27.73% at Fx1, Fx2, Fx3, Fx4 and Fx5, p < 0.05). There were 47 (47/88, 53.4%) lesions being accompanied by perilesional edema and the inter-fractional changes were significantly different compared to those without perilesional edema (p < 0.001). Patients with multiple lesions (13/28, 46.4%) had more significant inter-fractional tumor changes than those with single lesion (15/28, 53.6%), including tumor volume reduction and anatomical shift (p < 0.001). PTV coverage of non-adaptive plans was below the prescribed coverage in 26/140 fractions (19%), with 12 (9%) failing by more than 10%. All 140 adaptive fractions met prescribed target coverage. The adaptive plans also had lower dose to whole brain than non-adaptive plans (p < 0.001). Conclusions Significant inter-fractional tumor changes could be found during FSRT in patients with BMs treated on the 1.5 T MR-Linac. Daily MR-guided re-optimization of treatment plans showed dosimetric benefit in patients with perilesional edema or multiple lesions.
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Affiliation(s)
- Shouliang Ding
- Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Sun Yat‑sen University Cancer Center, Guangzhou, China
| | - Biaoshui Liu
- Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Sun Yat‑sen University Cancer Center, Guangzhou, China
| | - Shiyang Zheng
- Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Sun Yat‑sen University Cancer Center, Guangzhou, China
| | - Daquan Wang
- Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Sun Yat‑sen University Cancer Center, Guangzhou, China
| | - Mingzhi Liu
- Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Sun Yat‑sen University Cancer Center, Guangzhou, China
| | - Hongdong Liu
- Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Sun Yat‑sen University Cancer Center, Guangzhou, China
| | - Pengxin Zhang
- Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Sun Yat‑sen University Cancer Center, Guangzhou, China
| | - Kangqiang Peng
- Department of Radiology, State Key Laboratory of Oncology in South China, Sun Yat‑sen University Cancer Center, Guangzhou, China
| | - Haoqiang He
- Department of Radiology, State Key Laboratory of Oncology in South China, Sun Yat‑sen University Cancer Center, Guangzhou, China
| | - Rui Zhou
- Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Sun Yat‑sen University Cancer Center, Guangzhou, China
| | - Jinyu Guo
- Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Sun Yat‑sen University Cancer Center, Guangzhou, China
| | - Bo Qiu
- Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Sun Yat‑sen University Cancer Center, Guangzhou, China
| | - Xiaoyan Huang
- Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Sun Yat‑sen University Cancer Center, Guangzhou, China
| | - Hui Liu
- Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Sun Yat‑sen University Cancer Center, Guangzhou, China
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15
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Roh H, Lee SY, Lee J, Hwang SY, Kim JH. Use of thyroid transcription factor 1 and napsin A to predict local failure and survival after Gamma Knife radiosurgery in patients with brain metastases from lung adenocarcinoma. J Neurosurg 2023; 138:663-673. [PMID: 35962961 DOI: 10.3171/2022.6.jns22450] [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: 02/21/2022] [Accepted: 06/09/2022] [Indexed: 11/06/2022]
Abstract
OBJECTIVE Stereotactic radiosurgery (SRS), combined with contemporary targeted therapies and immunotherapies, has improved the overall survival of patients with lung adenocarcinoma (ADC). Given that histological subtypes reflect prognosis in patients with primary ADC, it is important to integrate pathological biomarkers to predict clinical outcomes after SRS in patients with brain metastases from lung ADC. Therefore, the authors investigated the prognostic relevance of various biomarkers of primary lung ADC for clinical outcomes after SRS. METHODS A total of 95 patients with 136 brain metastases (1-4 oligometastases) who were treated with Gamma Knife radiosurgery between January 2017 and December 2020 were included. The Kaplan-Meier method and univariate and multivariate analyses using Cox proportional hazard regression models were used to identify prognostic factors for local control, survival, and distant brain control. RESULTS Multivariate analysis revealed thyroid transcription factor 1 as an independent prognostic factor for local control (HR 0.098, 95% CI 0.014-0.698, p = 0.0203) and napsin A as a significant predictor of overall survival after SRS (HR 0.080, 95% CI 0.017-0.386, p < 0.01). In a subset analysis of epidermal growth factor receptor (EGFR) mutation, patients with EGFR exon 19 mutations showed better distant brain control than those with EGFR exon 21 mutations (p < 0.01). CONCLUSIONS Pathological biomarkers of primary cancer should be considered to predict clinical outcomes after SRS in patients with lung ADC. Use of such biomarkers may help to provide personalized treatment to each patient, improving clinical outcomes after SRS.
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Affiliation(s)
- Haewon Roh
- 1Department of Neurosurgery, Armed Forces Capital Hospital, Seongnam.,Departments of2Neurosurgery
| | | | - Jinhwan Lee
- 4Pathology, Guro Hospital, Korea University of Medicine, Seoul; and
| | - Soon-Young Hwang
- 5Department of Biostatistics, Korea University of Medicine, Seoul, Republic of Korea
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16
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Karz A, Dimitrova M, Kleffman K, Alvarez-Breckenridge C, Atkins MB, Boire A, Bosenberg M, Brastianos P, Cahill DP, Chen Q, Ferguson S, Forsyth P, Glitza Oliva IC, Goldberg SB, Holmen SL, Knisely JPS, Merlino G, Nguyen DX, Pacold ME, Perez-Guijarro E, Smalley KSM, Tawbi HA, Wen PY, Davies MA, Kluger HM, Mehnert JM, Hernando E. Melanoma central nervous system metastases: An update to approaches, challenges, and opportunities. Pigment Cell Melanoma Res 2022; 35:554-572. [PMID: 35912544 PMCID: PMC10171356 DOI: 10.1111/pcmr.13059] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2022] [Accepted: 07/29/2022] [Indexed: 01/27/2023]
Abstract
Brain metastases are the most common brain malignancy. This review discusses the studies presented at the third annual meeting of the Melanoma Research Foundation in the context of other recent reports on the biology and treatment of melanoma brain metastases (MBM). Although symptomatic MBM patients were historically excluded from immunotherapy trials, efforts from clinicians and patient advocates have resulted in more inclusive and even dedicated clinical trials for MBM patients. The results of checkpoint inhibitor trials were discussed in conversation with current standards of care for MBM patients, including steroids, radiotherapy, and targeted therapy. Advances in the basic scientific understanding of MBM, including the role of astrocytes and metabolic adaptations to the brain microenvironment, are exposing new vulnerabilities which could be exploited for therapeutic purposes. Technical advances including single-cell omics and multiplex imaging are expanding our understanding of the MBM ecosystem and its response to therapy. This unprecedented level of spatial and temporal resolution is expected to dramatically advance the field in the coming years and render novel treatment approaches that might improve MBM patient outcomes.
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Affiliation(s)
- Alcida Karz
- Department of Pathology, NYU Grossman School of Medicine, New York, USA.,Interdisciplinary Melanoma Cooperative Group, Perlmutter Cancer Center, NYU Langone Health, New York, USA
| | - Maya Dimitrova
- Interdisciplinary Melanoma Cooperative Group, Perlmutter Cancer Center, NYU Langone Health, New York, USA.,Department of Medicine, NYU Grossman School of Medicine, New York, USA
| | - Kevin Kleffman
- Department of Pathology, NYU Grossman School of Medicine, New York, USA.,Interdisciplinary Melanoma Cooperative Group, Perlmutter Cancer Center, NYU Langone Health, New York, USA
| | | | - Michael B Atkins
- Georgetown-Lombardi Comprehensive Cancer Center and Department of Oncology, Georgetown University Medical Center, Washington, District of Columbia, USA
| | - Adrienne Boire
- Human Oncology and Pathogenesis Program, Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, USA
| | - Marcus Bosenberg
- Laboratory of Cancer Biology and Genetics, Center for Cancer Research NCI, NIH, USA
| | - Priscilla Brastianos
- MGH Cancer Center, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Daniel P Cahill
- Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Qing Chen
- Immunology, Microenvironment and Metastasis Program, The Wistar Institute, Philadelphia, Pennsylvania, USA
| | - Sherise Ferguson
- Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Peter Forsyth
- Department of Neuro-Oncology and Tumor Biology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida, USA
| | - Isabella C Glitza Oliva
- Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Sarah B Goldberg
- Department of Medicine (Medical Oncology), Yale School of Medicine, New Haven, Connecticut, USA
| | - Sheri L Holmen
- Huntsman Cancer Institute and Department of Surgery, University of Utah Health Sciences Center, Salt Lake City, Utah, USA
| | - Jonathan P S Knisely
- Meyer Cancer Center and Department of Radiation Oncology, Weill Cornell Medicine, New York, New York, USA
| | - Glenn Merlino
- Laboratory of Cancer Biology and Genetics, Center for Cancer Research NCI, NIH, USA
| | - Don X Nguyen
- Department of Pathology, Yale Cancer Center, Yale University School of Medicine, New Haven, Connecticut, USA
| | - Michael E Pacold
- Department of Radiation Oncology, NYU Langone Health and NYU Grossman School of Medicine, New York, New York, USA
| | - Eva Perez-Guijarro
- Laboratory of Cancer Biology and Genetics, Center for Cancer Research NCI, NIH, USA
| | - Keiran S M Smalley
- Department of Tumor Biology, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA
| | - Hussein A Tawbi
- Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Patrick Y Wen
- Center for Neuro-Oncology, Dana-Farber Cancer Institute, United States, Boston, Massachusetts, USA
| | - Michael A Davies
- Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Harriet M Kluger
- Department of Medicine (Medical Oncology), Yale School of Medicine, New Haven, Connecticut, USA
| | - Janice M Mehnert
- Interdisciplinary Melanoma Cooperative Group, Perlmutter Cancer Center, NYU Langone Health, New York, USA.,Department of Medicine, NYU Grossman School of Medicine, New York, USA
| | - Eva Hernando
- Department of Pathology, NYU Grossman School of Medicine, New York, USA.,Interdisciplinary Melanoma Cooperative Group, Perlmutter Cancer Center, NYU Langone Health, New York, USA
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17
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Yoo J, Kim HJ, Kim SM, Park HH. Prognostic factors to predict the efficacy of surgical interventions against brain metastasis secondary to thyroid cancer. Eur Thyroid J 2022; 11:e220087. [PMID: 35900775 PMCID: PMC9346320 DOI: 10.1530/etj-22-0087] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2022] [Accepted: 06/29/2022] [Indexed: 11/22/2022] Open
Abstract
Introduction Brain metastasis in differentiated thyroid cancer (DTC) is rare (frequency < 1%) and has a poor prognosis. Treatment strategies for brain metastasis are not well established. Objectives We conducted a retrospective analysis to identify predictive factors for patient outcomes and verify surgical indications for patients with brain metastasis and DTC. Methods The study included 34 patients with pathologically confirmed DTC with brain metastasis from March 2008 to November 2020. The associations between overall survival (OS) and clinical factors were evaluated. Cox regression analysis was used to determine the relationship between clinical factors and OS. To assess the survival benefit of craniotomy, Kaplan-Meier survival analysis was performed for each variable whose statistical significance was determined by Cox regression analysis. Results The median OS of the entire patient sample was 11.4 months. Survival was affected by the presence of lung metastasis (P = 0.033) and the number of brain metastases (n > 3) (P = 0.039). Only the subgroup with the number of brain metastases ≤3 showed statistical significance in the subgroup analysis of survival benefit following craniotomy (P = 0.048). Conclusions The number of brain metastases and the existence of lung metastasis were regarded more essential than other clinical factors in patients with DTC in this study. Furthermore, craniotomies indicated a survival benefit only when the number of brain metastases was ≤3. This finding could be beneficial in determining surgical indications in thyroid cancer with brain metastasis.
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Affiliation(s)
- Jihwan Yoo
- Department of Neurosurgery, Brain Tumor Center, Gangnam Severance Hospital, Seoul, Republic of Korea
- College of Medicine, Yonsei University, Seoul, Republic of Korea
| | - Hee Jun Kim
- Department of Surgery, CHA Ilsan Medical Center, Cha University School of Medicine, Goyang-si, Republic of Korea
| | - Seok Mo Kim
- Department of Surgery, Thyroid Cancer Center, Gangnam Severance Hospital, Institute of Refractory Thyroid Cancer, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Hun Ho Park
- Department of Neurosurgery, Brain Tumor Center, Gangnam Severance Hospital, Seoul, Republic of Korea
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18
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Yoo J, Park HH, Kang SG, Chang JH. Recent Update on Neurosurgical Management of Brain Metastasis. Brain Tumor Res Treat 2022; 10:164-171. [PMID: 35929114 PMCID: PMC9353165 DOI: 10.14791/btrt.2022.0023] [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: 06/09/2022] [Revised: 06/22/2022] [Accepted: 06/25/2022] [Indexed: 11/20/2022] Open
Abstract
Brain metastasis (BM), classified as a secondary brain tumor, is the most common malignant central nervous system tumor whose median overall survival is approximately 6 months. However, the survival rate of patients with BMs has increased with recent advancements in immunotherapy and targeted therapy. This means that clinicians should take a more active position in the treatment paradigm that passively treats BMs. Because patients with BM are treated in a variety of clinical settings, treatment planning requires a more sophisticated decision-making process than that for other primary malignancies. Therefore, an accurate prognostic prediction is essential, for which a graded prognostic assessment that reflects next-generation sequencing can be helpful. It is also essential to understand the indications for various treatment modalities, such as surgical resection, stereotactic radiosurgery, and whole-brain radiotherapy and consider their advantages and disadvantages when choosing a treatment plan. Surgical resection serves a limited auxiliary function in BM, but it can be an essential therapeutic approach for increasing the survival rate of specific patients; therefore, this must be thoroughly recognized during the treatment process. The ultimate goal of surgical resection is maximal safe resection; to this end, neuronavigation, intraoperative neuro-electrophysiologic assessment including evoked potential, and the use of fluorescent materials could be helpful. In this review, we summarize the considerations for neurosurgical treatment in a rapidly changing treatment environment.
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Affiliation(s)
- Jihwan Yoo
- Department of Neurosurgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Hun Ho Park
- Department of Neurosurgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Seok-Gu Kang
- Department of Neurosurgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Jong Hee Chang
- Department of Neurosurgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
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19
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Tjong MC, Louie AV, Singh AK, Videtic G, Stephans K, Plumridge N, Harden S, Slotman BJ, Alongi F, Guckenberger M, Siva S. Single-Fraction Stereotactic Ablative Body Radiotherapy to the Lung - The Knockout Punch. Clin Oncol (R Coll Radiol) 2022; 34:e183-e194. [PMID: 35221140 DOI: 10.1016/j.clon.2022.02.004] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2021] [Revised: 01/19/2022] [Accepted: 02/07/2022] [Indexed: 12/12/2022]
Abstract
This overview summarises the current evidence on efficacy and safety of single-fraction stereotactic ablative body radiotherapy (SABR) for primary lung cancers and lung metastases, in comparison with the more widely adapted multi-fraction SABR regimens. A literature search using the Medline database through PubMed was carried out using the following key words: ('stereotactic' or 'sabr' or 'sbrt'), ('radiotherapy' or 'radiation therapy'), ('lung' or 'thorax' or 'thoracic' or 'chest'), ('cancer' or 'metasta-' or 'oligometasta-'), alongside: (i) ('single-fraction' or 'single-dose') to identify trials and cohort studies with single-fraction SABR to lung malignant tumours and (ii) ('fraction' or 'schedule') limiting the search to 'clinical trial' and 'randomized controlled trial' to ensure thorough capture of lung SABR trials comparing different fractionations. The review discusses the radiobiological, technical and organ at risk considerations of single-fraction SABR to the lung.
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Affiliation(s)
- M C Tjong
- Sunnybrook Odette Cancer Centre, Toronto, Ontario, Canada
| | - A V Louie
- Sunnybrook Odette Cancer Centre, Toronto, Ontario, Canada
| | - A K Singh
- Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA
| | - G Videtic
- The Cleveland Clinic, Cleveland, OH, USA
| | - K Stephans
- The Cleveland Clinic, Cleveland, OH, USA
| | - N Plumridge
- Peter MacCallum Cancer Centre, Melbourne, Australia
| | - S Harden
- Peter MacCallum Cancer Centre, Melbourne, Australia
| | - B J Slotman
- Amsterdam University Medical Centers/VUMC, Amsterdam, the Netherlands
| | - F Alongi
- Advanced Radiation Oncology Department, IRCCS Sacro Cuore-Don Calabria Hospital, Negrar-Verona, Italy; University of Brescia, Brescia, Italy
| | - M Guckenberger
- University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - S Siva
- Peter MacCallum Cancer Centre, Melbourne, Australia.
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20
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Pahwa B, Kurwale N, Agrawal D. Evaluation of periprocedural anxiety during Gamma Knife Radiosurgery (GKRS) Frame fixation for brain lesions. Clin Neurol Neurosurg 2022; 217:107242. [DOI: 10.1016/j.clineuro.2022.107242] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2022] [Revised: 03/14/2022] [Accepted: 04/04/2022] [Indexed: 11/15/2022]
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21
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Yoo J, Cha YJ, Park HH, Park M, Joo B, Suh SH, Ahn SJ. The Extent of Necrosis in Brain Metastases May Predict Subtypes of Primary Cancer and Overall Survival in Patients Receiving Craniotomy. Cancers (Basel) 2022; 14:cancers14071694. [PMID: 35406466 PMCID: PMC8997083 DOI: 10.3390/cancers14071694] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2022] [Revised: 03/23/2022] [Accepted: 03/24/2022] [Indexed: 02/04/2023] Open
Abstract
Although necrosis is common in brain metastasis (BM), its biological and clinical significances remain unknown. We evaluated necrosis extent differences by primary cancer subtype and correlated BM necrosis to overall survival post-craniotomy. We analyzed 145 BMs of patients receiving craniotomy. Necrosis to tumor ratio (NTR) was measured. Patients were divided into two groups by NTR: BMs with sparse necrosis and with abundant necrosis. Clinical features were compared. To investigate factor relevance for BM necrosis, multivariate logistic regression, random forests, and gradient boosting machine analyses were performed. Kaplan−Meier analysis and log-rank tests were performed to evaluate the effect of BM necrosis on overall survival. Lung cancer was a more common origin for BMs with abundant necrosis (42/72, 58.33%) versus sparse necrosis (23/73, 31.51%, p < 0.01). Primary cancer subtype and tumor volume were the most relevant factors for BM necrosis (p < 0.01). BMs harboring moderately abundant necrosis showed longer survival, versus sparse or highly abundant necrosis (p = 0.04). Lung cancer BM may carry larger necrosis than BMs from other cancers. Further, moderately abundant necrosis in BM may predict a good prognosis post-craniotomy.
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Affiliation(s)
- Jihwan Yoo
- Department of Neurosurgery, Brain Tumor Center, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06230, Korea; (J.Y.); (H.H.P.)
| | - Yoon Jin Cha
- Department of Pathology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06230, Korea;
| | - Hun Ho Park
- Department of Neurosurgery, Brain Tumor Center, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06230, Korea; (J.Y.); (H.H.P.)
| | - Mina Park
- Department of Radiology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06230, Korea; (M.P.); (B.J.); (S.H.S.)
| | - Bio Joo
- Department of Radiology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06230, Korea; (M.P.); (B.J.); (S.H.S.)
| | - Sang Hyun Suh
- Department of Radiology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06230, Korea; (M.P.); (B.J.); (S.H.S.)
| | - Sung Jun Ahn
- Department of Radiology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06230, Korea; (M.P.); (B.J.); (S.H.S.)
- Correspondence: ; Tel.: +82-2-2019-3510; Fax: +82-2-3462-5472
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22
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Kim JH, Choi JW, Kong DS, Seol HJ, Nam DH, Ryu JW, Kim ST, Suh YL, Lee JI. Histopathology and surgical outcome of symptomatic treatment-related changes after gamma knife radiosurgery in patients with brain metastases. Sci Rep 2022; 12:3013. [PMID: 35194082 PMCID: PMC8863779 DOI: 10.1038/s41598-022-06881-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2021] [Accepted: 02/07/2022] [Indexed: 01/07/2023] Open
Abstract
A late-onset treatment-related changes (TRCs), which represent radiographic radiation necrosis (RN), frequently occur after stereotactic radiosurgery (SRS) for brain metastases and often need surgical treatment. This study aimed to validate the true pathology and investigate clinical implication of surgically resected TRCs on advanced magnetic resonance imaging (MRI). Retrospective analyses of 86 patients who underwent surgical resection after radiosurgery of brain metastases were performed. Fifty-four patients displayed TRCs on preoperative MRI, comprising pure RN in 19 patients (TRC-RN group) and mixed viable tumor cells in 35 patients (TRC-PD group). Thirty-two patients revealed the consistent diagnosis of progressive disease in both MRI and histopathology (PD-PD group). The TRC-PD group showed larger prescription isodose volume (9.4 cm3) than the TRC-RN (4.06 cm3, p = 0.014) group and a shorter time interval from SRS to preoperative MRI diagnosis (median 4.07 months) than the PD-PD group (median 8.77 months, p = 0.004). Progression-free survival was significantly different among the three groups (p < 0.001), but not between TRC-RN and TRC-PD (post hoc test, p = 1.00), while no difference was observed in overall survival (p = 0.067). Brain metastases featured as TRCs after SRS frequently contained viable tumor cells. However, this histologic heterogeneity had a minor impact on benign local prognosis of TRCs after surgical resection.
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Affiliation(s)
- Jeong-Hwa Kim
- Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, South Korea
| | - Jung-Won Choi
- Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, South Korea
| | - Doo-Sik Kong
- Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, South Korea
| | - Ho Jun Seol
- Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, South Korea
| | - Do-Hyun Nam
- Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, South Korea
| | - Jae-Wook Ryu
- Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Sung-Tae Kim
- Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Yeon-Lim Suh
- Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Jung-Il Lee
- Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, South Korea.
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23
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Latorzeff I, Antoni D, Josset S, Noël G, Tallet-Richard A. Radiation therapy for brain metastases. Cancer Radiother 2021; 26:129-136. [PMID: 34955413 DOI: 10.1016/j.canrad.2021.11.010] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
We present the update of the recommendations of the French society for radiation oncology on radiation therapy for the management of brain metastases. It has evolved in recent years and has become more complex. As the life expectancy of patients has increased and retreatments have become more frequent, side effects must be absolutely avoided. Cognitive side effects must in particular be prevented, and the most modern radiation therapy techniques must be used systematically. New prognostic classifications specific to the primary tumour of patients, advances in imaging and radiation therapy technology and new systemic therapeutic strategies, are making treatment more relevant. Stereotactic radiation therapy has supplanted whole-brain radiation therapy both for patients with metastases in place and for those who underwent surgery. Hippocampus protection is possible with intensity-modulated radiation therapy. Its relevance in terms of cognitive functioning should be more clearly demonstrated but the requirement for its use is constantly increasing. New targeted cancer treatment therapies based on the nature of the primitive have complicated the notion of the place and timing of radiation therapy and the discussion during multidisciplinary care meeting to indicate the best sequences is becoming a challenging issue as data on the interaction between treatments remain to be documented. In the end, although aimed at patients in the palliative phase, the management of brain metastases is one of the locations for which technical reflection is the most challenging and treatment become increasingly personalized.
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Affiliation(s)
- I Latorzeff
- Service de radiothérapie, groupe Oncorad Garonne, clinique Pasteur, l'« Atrium », 1, rue de la Petite-Vitesse, 31300 Toulouse, France; Centre régional de radiochirurgie stéréotaxique, CHU Rangueil, avenue Jean-Poulhès, 31052 Toulouse cedex, France.
| | - D Antoni
- Département universitaire de radiothérapie, centre Paul-Strauss, Unicancer, 3, rue de la Porte-de-l'Hôpital, 67065 Strasbourg cedex, France
| | - S Josset
- Service de physique médicale, institut de cancérologie de l'Ouest, Unicancer, 44805 Saint-Herblain, France
| | - G Noël
- Département universitaire de radiothérapie, centre Paul-Strauss, Unicancer, 3, rue de la Porte-de-l'Hôpital, 67065 Strasbourg cedex, France
| | - A Tallet-Richard
- Département universitaire de radiothérapie, institut Paoli-Calmettes, Unicancer, 232, boulevard de Sainte-Marguerite, 13273 Marseille, France
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24
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Punchak M, Miranda SP, Gutierrez A, Brem S, O'Rourke D, Lee JYK, Shabason JE, Petrov D. Resecting the dominant lesion: Patient outcomes after surgery and radiosurgery vs stand-alone radiosurgery in the setting of multiple brain metastases. Clin Neurol Neurosurg 2021; 211:107016. [PMID: 34823154 DOI: 10.1016/j.clineuro.2021.107016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2021] [Revised: 09/17/2021] [Accepted: 10/31/2021] [Indexed: 11/17/2022]
Abstract
BACKGROUND Brain metastases are the most common central nervous system (CNS) tumors, occurring in 300,000 people per year in the US. While there are immediate local benefits to surgical resection for dominant lesions, including reduction of tumor burden and edema, the survival benefits of surgical resection, over radiosurgery, remains unclear. METHODS The University of Pennsylvania Health System database was retrospectively reviewed for patients presenting with multiple brain metastases from 1/1/16-8/31/18 with one dominant lesion > 2 cm in diameter, who underwent initial treatment with either resection of the dominant lesion or Gamma Knife radiosurgery (GKS). Inclusion criteria were age > 18, > 1 brain metastasis, and presence of a dominant lesion (>2 cm). We analyzed factors associated with mortality. RESULTS 129 patients were identified (surgery=84, GKS=45). The median number of intracranial metastases was 3 (IQR: 2-5). The median diameter of the largest lesion was 31 mm (IQR: 25-38) in the surgery group vs 21 mm (IQR: 20-24) in the GKS group (p < 0.001). Mortality did not differ between surgery and GKS patients (69.1% vs 77.8%, p = 0.292). In a multivariate survival analysis, there was no difference in mortality between the surgery and GKS cohorts (aHR: 1.35, 95% CI: 0.74-2.45 p = 0.32). Pre-operative KPS (aHR: 0.97, 95% CI: 0.95-0.99, p = 0.004), CNS radiotherapy (aHR: 0.33, 95% CI: 0.19-0.56 p < 0.001), chemotherapy (aHR: 0.27, 95% CI: 0.15-0.47, p < 0.001), and immunotherapy (aHR: 0.41, 95% CI: 0.25-0.68, p = 0.001) were associated with decreased mortality. CONCLUSION In our institution, patients with multiple brain metastases and one symptomatic dominant lesion demonstrated similar survival after GKS when compared with up-front surgical resection of the dominant lesion.
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Affiliation(s)
- Maria Punchak
- Department of Neurosurgery, University of Pennsylvania Health System, Philadelphia, USA
| | - Stephen P Miranda
- Department of Neurosurgery, University of Pennsylvania Health System, Philadelphia, USA
| | - Alexis Gutierrez
- Department of Neurosurgery, University of Pennsylvania Health System, Philadelphia, USA
| | - Steven Brem
- Department of Neurosurgery, University of Pennsylvania Health System, Philadelphia, USA
| | - Donald O'Rourke
- Department of Neurosurgery, University of Pennsylvania Health System, Philadelphia, USA
| | - John Y K Lee
- Department of Neurosurgery, University of Pennsylvania Health System, Philadelphia, USA
| | - Jacob E Shabason
- Deparment of Radiation Oncology, University of Pennsylvania Health System, Philadelphia, USA
| | - Dmitriy Petrov
- Department of Neurosurgery, University of Pennsylvania Health System, Philadelphia, USA.
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25
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de Vries M, Klaassen NJM, Morsink NC, van Nimwegen SA, Nijsen JFW, van den Dobbelsteen JJ. Dedicated holmium microsphere administration device for MRI-guided interstitial brain microbrachytherapy. Med Eng Phys 2021; 96:13-21. [PMID: 34565548 DOI: 10.1016/j.medengphy.2021.07.009] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2020] [Revised: 07/15/2021] [Accepted: 07/21/2021] [Indexed: 01/22/2023]
Abstract
Microbrachytherapy with radioactive holmium-166 (166Ho) microspheres (MS) has the potential to be an effective treatment method for brain malignancies. Direct intratumoural delivery of 166Ho-MS and dose coverage of the whole tumour are crucial requirements. However, currently no dedicated instruments for controlled intratumoural delivery exist. This study presents an administration device that facilitates this novel magnetic resonance imaging (MRI) -guided intervention. The bioceramic alumina oxide cannula creates a straight channel for a superelastic nitinol precurved stylet to control spatial deposition of Ho-MS. End-point accuracy of the stylet was measured during insertions in phantoms. Imaging tests were performed in a 3 Tesla MRI-scanner to quantify instrument-induced artefacts. Additionally, the feasibility of non-radioactive holmium-165 (165Ho)-MS delivery with the administration device was evaluated in a brain tumour simulant. Absolute stylet tip error was 0.88 ± 0.61 mm, instrument distortion in MRI depended on needle material and orientation and dose delivery of 165Ho-MS in a brain tumour phantom was possible. This study shows that the administration device can accurately place the stylet for injection of Ho-MS and that visualization can be performed with MRI.
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Affiliation(s)
- M de Vries
- Department of BioMechanical Engineering, Faculty of Mechanical, Maritime and Materials Engineering, Delft University of Technology, Mekelweg 2, Delft 2628 CD, the Netherlands.
| | - N J M Klaassen
- Department of Medical Imaging, Radboud Institute for Health Sciences, Radboud university Medical Center, Geert Grooteplein Zuid 10, Nijmegen 6525 GA, the Netherlands
| | - N C Morsink
- Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 108, Utrecht 3508 TD, the Netherlands
| | - S A van Nimwegen
- Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 108, Utrecht 3508 TD, the Netherlands
| | - J F W Nijsen
- Department of Medical Imaging, Radboud Institute for Health Sciences, Radboud university Medical Center, Geert Grooteplein Zuid 10, Nijmegen 6525 GA, the Netherlands; Quirem Medical B.V., Zutphenseweg 55, Deventer 7418 AH, the Netherlands
| | - J J van den Dobbelsteen
- Department of BioMechanical Engineering, Faculty of Mechanical, Maritime and Materials Engineering, Delft University of Technology, Mekelweg 2, Delft 2628 CD, the Netherlands
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Al-Wassia RK, Iskanderani O. Stereotactic Radiosurgery (SRS) experience on brain metastases: A 3-year retrospective study at King Abdulaziz University Hospital. Saudi J Biol Sci 2021; 28:5042-5047. [PMID: 34466080 PMCID: PMC8381001 DOI: 10.1016/j.sjbs.2021.05.017] [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: 03/06/2021] [Revised: 05/04/2021] [Accepted: 05/05/2021] [Indexed: 11/30/2022] Open
Abstract
Objectives Stereotactic radiosurgery (SRS), a non-invasive surgical procedure had been utilized for treatment of patients with brain metastases. This study aims to determine the survival, local control of brain metastases and treatment outcome to SRS-treated patients based on radiological imaging. Methods The MRI scans of SRS-treated patients with brain metastases (n = 24) from the Radiology Department of King Abdulaziz University from January 2016 to September 2019 were examined. The data was analyzed using descriptive statistics and Chi-square test. Results Out of 24 patients, most had brain metastases (95.8%, n = 23) with mean interval development (after primary site) of 21.88 ± 25.2 months. Radiological imaging revealed tumor characteristics of smallest (n = 11) and biggest lesions (n = 24) of patients to be 0.98 ± 0.7 and 2.23 ± 0.9, respectively and number of lesion to be 4-5 lesions (n = 3), 3 lesions (n = 6), 2 lesions (n = 4) and 1 lesion (n = 11). After SRS treatment, findings showed 17.6% (n = 3) no recurrence among the patients. Those with recurrences have decrease in lesion enhancement (11.8%, n = 2), decrease in size (29.4%, n = 5) and decrease in both enhancement and size (29.4%). Overall survival obtained was 16.7% (n = 2) at 313.83 ± 376.0 days (n = 23) survival period. Chi-square test showed that radiological findings were significantly associated with tumor recurrence (p = 0.010), having SRS-treated patients with recurrences (n = 12) to experience significant decrease (p = 0.010) in tumor enhancement, size, and both enhancement and size. Conclusion A significant decrease in tumor size and enhancement was observed in SRS-treated patients, suggesting SRS treatment to have associated benefit with prolonged survival duration.
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Affiliation(s)
- Rolina K Al-Wassia
- Department of Radiology, Radiation Oncology Unit, King Abdulaziz University Hospital, P.O. Box 80200, Jeddah 21589, Saudi Arabia
| | - Omar Iskanderani
- Department of Radiology, Radiation Oncology Unit, King Abdulaziz University Hospital, P.O. Box 80200, Jeddah 21589, Saudi Arabia
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Di Nunno V, Franceschi E, Tosoni A, Mura A, Minichillo S, Di Battista M, Gatto L, Maggio I, Lodi R, Bartolini S, Brandes AA. Is Molecular Tailored-Therapy Changing the Paradigm for CNS Metastases in Breast Cancer? Clin Drug Investig 2021; 41:757-773. [PMID: 34403132 DOI: 10.1007/s40261-021-01070-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/25/2021] [Indexed: 11/28/2022]
Abstract
Breast cancer (BC) is the second most common tumour spreading to the central nervous system (CNS). The prognosis of patients with CNS metastases depends on several parameters including the molecular assessment of the disease. Although loco-regional treatment remains the best approach, systemic therapies are acquiring a role leading to remarkable long-lasting responses. The efficacy of these compounds diverges between tumours with different molecular assessments. Promising agents under investigation are drugs targeting the HER2 pathways such as tucatinib, neratinib, pyrotinib, trastuzumab deruxtecan. In addition, there are several promising agents under investigation for patients with triple-negative brain metastases (third-generation taxane, etirinotecan, sacituzumab, immune-checkpoint inhibitors) and hormone receptor-positive brain metastases (CDK 4/5, phosphoinositide-3-kinase-mammalian target of rapamycin [PI3K/mTOR] inhibitors). Also, the systemic treatment of leptomeningeal metastases, which represents a very negative prognostic site of metastases, is likely to change as several compounds are under investigation, some with interesting preliminary results. Here we performed a comprehensive review focusing on the current management of CNS metastases according to molecular subtypes, site of metastases (leptomeningeal vs brain), and systemic treatments under investigation.
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Affiliation(s)
- Vincenzo Di Nunno
- Department of Oncology, AUSL Bologna, Via Altura 3, 40139, Bologna, Italy.
| | - Enrico Franceschi
- Department of Oncology, AUSL Bologna, Via Altura 3, 40139, Bologna, Italy
| | - Alicia Tosoni
- Department of Oncology, AUSL Bologna, Via Altura 3, 40139, Bologna, Italy
| | - Antonella Mura
- Department of Oncology, AUSL Bologna, Via Altura 3, 40139, Bologna, Italy
| | - Santino Minichillo
- Department of Oncology, AUSL Bologna, Via Altura 3, 40139, Bologna, Italy
| | - Monica Di Battista
- Department of Oncology, AUSL Bologna, Via Altura 3, 40139, Bologna, Italy
| | - Lidia Gatto
- Department of Oncology, AUSL Bologna, Via Altura 3, 40139, Bologna, Italy
| | - Ilaria Maggio
- Department of Oncology, AUSL Bologna, Via Altura 3, 40139, Bologna, Italy
| | - Raffaele Lodi
- IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy
| | - Stefania Bartolini
- Department of Oncology, AUSL Bologna, Via Altura 3, 40139, Bologna, Italy
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Azoulay M, Chang SD, Gibbs IC, Hancock SL, Pollom EL, Harsh GR, Adler JR, Harraher C, Li G, Hayden Gephart M, Nagpal S, Thomas RP, Recht LD, Jacobs LR, Modlin LA, Wynne J, Seiger K, Fujimoto D, Usoz M, von Eyben R, Choi CYH, Soltys SG. A phase I/II trial of 5-fraction stereotactic radiosurgery with 5-mm margins with concurrent temozolomide in newly diagnosed glioblastoma: primary outcomes. Neuro Oncol 2021; 22:1182-1189. [PMID: 32002547 DOI: 10.1093/neuonc/noaa019] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND We sought to determine the maximum tolerated dose (MTD) of 5-fraction stereotactic radiosurgery (SRS) with 5-mm margins delivered with concurrent temozolomide in newly diagnosed glioblastoma (GBM). METHODS We enrolled adult patients with newly diagnosed glioblastoma to 5 days of SRS in a 3 + 3 design on 4 escalating dose levels: 25, 30, 35, and 40 Gy. Dose limiting toxicity (DLT) was defined as Common Terminology Criteria for Adverse Events grades 3-5 acute or late CNS toxicity, including adverse radiation effect (ARE), the imaging correlate of radiation necrosis. RESULTS From 2010 to 2015, thirty patients were enrolled. The median age was 66 years (range, 51-86 y). The median target volume was 60 cm3 (range, 14.7-137.3 cm3). DLT occurred in 2 patients: one for posttreatment cerebral edema and progressive disease at 3 weeks (grade 4, dose 40 Gy); another patient died 1.5 weeks following SRS from postoperative complications (grade 5, dose 40 Gy). Late grades 1-2 ARE occurred in 8 patients at a median of 7.6 months (range 3.2-12.6 mo). No grades 3-5 ARE occurred. With a median follow-up of 13.8 months (range 1.7-64.4 mo), the median survival times were: progression-free survival, 8.2 months (95% CI: 4.6-10.5); overall survival, 14.8 months (95% CI: 10.9-19.9); O6-methylguanine-DNA methyltransferase hypermethylated, 19.9 months (95% CI: 10.5-33.5) versus 11.3 months (95% CI: 8.9-17.6) for no/unknown hypermethylation (P = 0.03), and 27.2 months (95% CI: 11.2-48.3) if late ARE occurred versus 11.7 months (95% CI: 8.9-17.6) for no ARE (P = 0.08). CONCLUSIONS The per-protocol MTD of 5-fraction SRS with 5-mm margins with concurrent temozolomide was 40 Gy in 5 fractions. ARE was limited to grades 1-2 and did not statistically impact survival.
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Affiliation(s)
- Melissa Azoulay
- Department of Radiation Oncology, Stanford University, Stanford, California, USA.,Department of Radiation Oncology, McGill University Health Centre, Montreal, Quebec, Canada
| | - Steven D Chang
- Department of Neurosurgery, Stanford University, Stanford, California, USA
| | - Iris C Gibbs
- Department of Radiation Oncology, Stanford University, Stanford, California, USA
| | - Steven L Hancock
- Department of Radiation Oncology, Stanford University, Stanford, California, USA
| | - Erqi L Pollom
- Department of Radiation Oncology, Stanford University, Stanford, California, USA
| | - Griffith R Harsh
- Department of Neurosurgery, Stanford University, Stanford, California, USA
| | - John R Adler
- Department of Neurosurgery, Stanford University, Stanford, California, USA
| | - Ciara Harraher
- Department of Neurosurgery, Stanford University, Stanford, California, USA
| | - Gordon Li
- Department of Neurosurgery, Stanford University, Stanford, California, USA
| | | | - Seema Nagpal
- Department of Neurology, Stanford University, Stanford, California, USA
| | - Reena P Thomas
- Department of Neurology, Stanford University, Stanford, California, USA
| | - Lawrence D Recht
- Department of Neurology, Stanford University, Stanford, California, USA
| | - Lisa R Jacobs
- Department of Radiation Oncology, Stanford University, Stanford, California, USA
| | - Leslie A Modlin
- Department of Radiation Oncology, Stanford University, Stanford, California, USA
| | - Jacob Wynne
- Department of Radiation Oncology, Stanford University, Stanford, California, USA
| | - Kira Seiger
- Department of Radiation Oncology, Stanford University, Stanford, California, USA
| | - Dylann Fujimoto
- Department of Radiation Oncology, Stanford University, Stanford, California, USA
| | - Melissa Usoz
- Department of Radiation Oncology, Stanford University, Stanford, California, USA
| | - Rie von Eyben
- Department of Radiation Oncology, Stanford University, Stanford, California, USA
| | - Clara Y H Choi
- Department of Radiation Oncology, Stanford University, Stanford, California, USA.,Department of Radiation Oncology, Santa Clara Valley Medical Center, San Jose, California, USA
| | - Scott G Soltys
- Department of Radiation Oncology, Stanford University, Stanford, California, USA
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29
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Aydin S, Esen Aydin A, Yuksel O, Tanriverdi T. Secondary Parkinsonism in a Patient With a Cerebral Cavernous Hemangioma Treated With Stereotactic Radiosurgery. Cureus 2021; 13:e14128. [PMID: 33927936 PMCID: PMC8075824 DOI: 10.7759/cureus.14128] [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] [Accepted: 03/26/2021] [Indexed: 11/06/2022] Open
Abstract
Secondary parkinsonism is defined with some symptoms similar to idiopathic Parkinson's disease, but with different etiologies. And cerebral cavernous hemangioma is one of the rare cases. A 51-year-old, male patient was consulted with tremor, rigidity and bradykinesia on the right upper extremity. The Hoehn and Yahr Parkinson's scale was Stage І. Radiological evaluations showed a deep-seated cerebral cavernous hemangioma at the left posterior insular region. The patient received stereotactic radiosurgery (CyberKnife®, Accuray Incorporated, Sunnyvale, CA, USA). Clinical and radiological improvements revealed within follow-up, respectively. Stereotactic radiosurgery may be an alternative treatment for secondary parkinsonism by reducing the risk of re-bleeding and reducing its size.
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Affiliation(s)
- Seckin Aydin
- Department of Neurosurgery, Prof. Dr. Cemil Tascioglu City Hospital, University of Health Sciences, Istanbul, TUR
| | - Aysegul Esen Aydin
- Department of Neurosurgery, Bakirkoy Research and Training Hospital for Neurology, Neurosurgery and Psychiatry, Istanbul, TUR
| | - Odhan Yuksel
- Department of Neurosurgery, Baskent University School Medicine, Alanya Teaching and Medical Research Center, Alanya, TUR
| | - Taner Tanriverdi
- Department of Neurosurgery, Cerrahpasa Medical Faculty, Istanbul University-Cerrahpasa, İstanbul, TUR
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30
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Pennig L, Shahzad R, Caldeira L, Lennartz S, Thiele F, Goertz L, Zopfs D, Meißner AK, Fürtjes G, Perkuhn M, Kabbasch C, Grau S, Borggrefe J, Laukamp KR. Automated Detection and Segmentation of Brain Metastases in Malignant Melanoma: Evaluation of a Dedicated Deep Learning Model. AJNR Am J Neuroradiol 2021; 42:655-662. [PMID: 33541907 DOI: 10.3174/ajnr.a6982] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2020] [Accepted: 10/21/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND PURPOSE Malignant melanoma is an aggressive skin cancer in which brain metastases are common. Our aim was to establish and evaluate a deep learning model for fully automated detection and segmentation of brain metastases in patients with malignant melanoma using clinical routine MR imaging. MATERIALS AND METHODS Sixty-nine patients with melanoma with a total of 135 brain metastases at initial diagnosis and available multiparametric MR imaging datasets (T1-/T2-weighted, T1-weighted gadolinium contrast-enhanced, FLAIR) were included. A previously established deep learning model architecture (3D convolutional neural network; DeepMedic) simultaneously operating on the aforementioned MR images was trained on a cohort of 55 patients with 103 metastases using 5-fold cross-validation. The efficacy of the deep learning model was evaluated using an independent test set consisting of 14 patients with 32 metastases. Manual segmentations of metastases in a voxelwise manner (T1-weighted gadolinium contrast-enhanced imaging) performed by 2 radiologists in consensus served as the ground truth. RESULTS After training, the deep learning model detected 28 of 32 brain metastases (mean volume, 1.0 [SD, 2.4] cm3) in the test cohort correctly (sensitivity of 88%), while false-positive findings of 0.71 per scan were observed. Compared with the ground truth, automated segmentations achieved a median Dice similarity coefficient of 0.75. CONCLUSIONS Deep learning-based automated detection and segmentation of brain metastases in malignant melanoma yields high detection and segmentation accuracy with false-positive findings of <1 per scan.
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Affiliation(s)
- L Pennig
- From the Institute for Diagnostic and Interventional Radiology (L.P., R.S., L.C., S.L., F.T., D.Z., M.P., C.K., J.B., K.R.L.)
| | - R Shahzad
- From the Institute for Diagnostic and Interventional Radiology (L.P., R.S., L.C., S.L., F.T., D.Z., M.P., C.K., J.B., K.R.L.).,Philips Innovative Technologies (R.S., F.T., M.P.), Aachen, Germany
| | - L Caldeira
- From the Institute for Diagnostic and Interventional Radiology (L.P., R.S., L.C., S.L., F.T., D.Z., M.P., C.K., J.B., K.R.L.)
| | - S Lennartz
- From the Institute for Diagnostic and Interventional Radiology (L.P., R.S., L.C., S.L., F.T., D.Z., M.P., C.K., J.B., K.R.L.)
| | - F Thiele
- From the Institute for Diagnostic and Interventional Radiology (L.P., R.S., L.C., S.L., F.T., D.Z., M.P., C.K., J.B., K.R.L.).,Philips Innovative Technologies (R.S., F.T., M.P.), Aachen, Germany
| | - L Goertz
- Center for Neurosurgery (L.G., G.F., S.G.), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
| | - D Zopfs
- From the Institute for Diagnostic and Interventional Radiology (L.P., R.S., L.C., S.L., F.T., D.Z., M.P., C.K., J.B., K.R.L.)
| | - A-K Meißner
- Department of Stereotaxy and Functional Neurosurgery (A.-K.M., G.F.), Center for Neurosurgery, University Hospital Cologne, Cologne, Germany
| | - G Fürtjes
- Center for Neurosurgery (L.G., G.F., S.G.), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.,Department of Stereotaxy and Functional Neurosurgery (A.-K.M., G.F.), Center for Neurosurgery, University Hospital Cologne, Cologne, Germany
| | - M Perkuhn
- From the Institute for Diagnostic and Interventional Radiology (L.P., R.S., L.C., S.L., F.T., D.Z., M.P., C.K., J.B., K.R.L.).,Philips Innovative Technologies (R.S., F.T., M.P.), Aachen, Germany
| | - C Kabbasch
- From the Institute for Diagnostic and Interventional Radiology (L.P., R.S., L.C., S.L., F.T., D.Z., M.P., C.K., J.B., K.R.L.)
| | - S Grau
- Center for Neurosurgery (L.G., G.F., S.G.), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
| | - J Borggrefe
- From the Institute for Diagnostic and Interventional Radiology (L.P., R.S., L.C., S.L., F.T., D.Z., M.P., C.K., J.B., K.R.L.)
| | - K R Laukamp
- From the Institute for Diagnostic and Interventional Radiology (L.P., R.S., L.C., S.L., F.T., D.Z., M.P., C.K., J.B., K.R.L.) .,Department of Radiology (K.R.L.), University Hospitals Cleveland Medical Center, Cleveland, Ohio.,Department of Radiology (K.R.L.), Case Western Reserve University, Cleveland, Ohio
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31
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Zhou Z, Sanders JW, Johnson JM, Gule-Monroe M, Chen M, Briere TM, Wang Y, Son JB, Pagel MD, Ma J, Li J. MetNet: Computer-aided segmentation of brain metastases in post-contrast T1-weighted magnetic resonance imaging. Radiother Oncol 2020; 153:189-196. [DOI: 10.1016/j.radonc.2020.09.016] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2020] [Revised: 08/26/2020] [Accepted: 09/08/2020] [Indexed: 12/25/2022]
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Nabors LB, Portnow J, Ahluwalia M, Baehring J, Brem H, Brem S, Butowski N, Campian JL, Clark SW, Fabiano AJ, Forsyth P, Hattangadi-Gluth J, Holdhoff M, Horbinski C, Junck L, Kaley T, Kumthekar P, Loeffler JS, Mrugala MM, Nagpal S, Pandey M, Parney I, Peters K, Puduvalli VK, Robins I, Rockhill J, Rusthoven C, Shonka N, Shrieve DC, Swinnen LJ, Weiss S, Wen PY, Willmarth NE, Bergman MA, Darlow SD. Central Nervous System Cancers, Version 3.2020, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 2020; 18:1537-1570. [PMID: 33152694 DOI: 10.6004/jnccn.2020.0052] [Citation(s) in RCA: 286] [Impact Index Per Article: 57.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
The NCCN Guidelines for Central Nervous System (CNS) Cancers focus on management of adult CNS cancers ranging from noninvasive and surgically curable pilocytic astrocytomas to metastatic brain disease. The involvement of an interdisciplinary team, including neurosurgeons, radiation therapists, oncologists, neurologists, and neuroradiologists, is a key factor in the appropriate management of CNS cancers. Integrated histopathologic and molecular characterization of brain tumors such as gliomas should be standard practice. This article describes NCCN Guidelines recommendations for WHO grade I, II, III, and IV gliomas. Treatment of brain metastases, the most common intracranial tumors in adults, is also described.
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Affiliation(s)
| | | | - Manmeet Ahluwalia
- 3Case Comprehensive Cancer Center/University Hospitals Seidman Cancer Center and Cleveland Clinic Taussig Cancer Institute
| | | | - Henry Brem
- 5The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
| | - Steven Brem
- 6Abramson Cancer Center at the University of Pennsylvania
| | | | - Jian L Campian
- 8Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine
| | | | | | | | | | | | - Craig Horbinski
- 13Robert H. Lurie Comprehensive Cancer Center of Northwestern University
| | - Larry Junck
- 14University of Michigan Rogel Cancer Center
| | | | - Priya Kumthekar
- 13Robert H. Lurie Comprehensive Cancer Center of Northwestern University
| | | | | | | | - Manjari Pandey
- 19St. Jude Children's Research Hospital/The University of Tennessee Health Science Center
| | | | | | - Vinay K Puduvalli
- 21The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute
| | - Ian Robins
- 22University of Wisconsin Carbone Cancer Center
| | - Jason Rockhill
- 23Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance
| | | | | | | | - Lode J Swinnen
- 5The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
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Sayan M, Mustafayev TZ, Balmuk A, Mamidanna S, Kefelioglu ESS, Gungor G, Chundury A, Ohri N, Karaarslan E, Ozyar E, Atalar B. Management of symptomatic radiation necrosis after stereotactic radiosurgery and clinical factors for treatment response. Radiat Oncol J 2020; 38:176-180. [PMID: 33012145 PMCID: PMC7533401 DOI: 10.3857/roj.2020.00171] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2020] [Revised: 06/26/2020] [Accepted: 07/06/2020] [Indexed: 01/31/2023] Open
Abstract
PURPOSE Approximately 10% of patients who received brain stereotactic radiosurgery (SRS) develop symptomatic radiation necrosis (RN). We sought to determine the effectiveness of treatment options for symptomatic RN, based on patient-reported outcomes. MATERIALS AND METHODS We conducted a retrospective review of 217 patients with 414 brain metastases treated with SRS from 2009 to 2018 at our institution. Symptomatic RN was determined by appearance on serial magnetic resonance images (MRIs), MR spectroscopy, requirement of therapy, and development of new neurological complaints without evidence of disease progression. Therapeutic interventions for symptomatic RN included corticosteroids, bevacizumab and/or surgical resection. Patient-reported therapeutic outcomes were graded as complete response (CR), partial response (PR), and no response. RESULTS Twenty-six patients experienced symptomatic RN after treatment of 50 separate lesions. The mean prescription dose was 22 Gy (range, 15 to 30 Gy) in 1 to 5 fractions (median, 1 fraction). Of the 12 patients managed with corticosteroids, 6 patients (50%) reported CR and 4 patients (33%) PR. Of the 6 patients managed with bevacizumab, 3 patients (50%) reported CR and 1 patient (18%) PR. Of the 8 patients treated with surgical resection, all reported CR (100%). Other than surgical resection, age ≥54 years (median, 54 years; range, 35 to 81 years) was associated with CR (odds ratio = 8.40; 95% confidence interval, 1.27-15.39; p = 0.027). CONCLUSION Corticosteroids and bevacizumab are commonly utilized treatment modalities with excellent response rate. Our results suggest that patient's age is associated with response rate and could help guide treatment decisions for unresectable symptomatic RN.
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Affiliation(s)
- Mutlay Sayan
- Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA
| | | | - Aykut Balmuk
- School of Medicine, Mehmet Ali Aydinlar Acibadem University, Istanbul, Turkey
| | - Swati Mamidanna
- Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA
| | | | - Gorkem Gungor
- Institute of Health Sciences, Mehmet Ali Aydinlar Acibadem University, Istanbul, Turkey
| | - Anupama Chundury
- Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA
| | - Nisha Ohri
- Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA
| | - Ercan Karaarslan
- Department of Radiology, School of Medicine, Mehmet Ali Aydinlar Acibadem University, Istanbul, Turkey
| | - Enis Ozyar
- School of Medicine, Mehmet Ali Aydinlar Acibadem University, Istanbul, Turkey
| | - Banu Atalar
- School of Medicine, Mehmet Ali Aydinlar Acibadem University, Istanbul, Turkey
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Abstract
Background:
Drug delivery to cancerous brain is a challenging task as it is
surrounded by an efficient protective barrier. The main hurdles for delivery of bioactive
molecules to cancerous brain are blood brain barrier (BBB), the invasive nature of gliomas,
drug resistance, and difficult brain interstitium transportation. Therefore, treatment
of brain cancer with the available drug regimen is difficult and has shown little improvement
in recent years.
Methods:
We searched about recent advancements in the use of nanomedicine for effective
treatment of the brain cancer. We focused on the use of liposomes, nanoparticles,
polymeric micelles, and dendrimers to improve brain cancer therapy.
Results:
Nanomedicines are well suited for the treatment of brain cancer owing to their
highly acceptable biological, chemical, and physical properties. Smaller size of nanomedicines
also enhances their anticancer potential and penetration into blood brain barrier
(BBB).
Conclusion:
Recently, nanomedicine based approaches have been developed and investigated
for effective treatment of brain cancer. Some of these have been translated into
clinical practice, in order to attain therapeutic needs of gliomas. Future advancements in
nanomedicines will likely produce significant changes in methods and practice of brain
cancer therapy.
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Affiliation(s)
- Shivani Verma
- I. K. Gujral Punjab Technical University, Jalandhar-Punjab 144601, India
| | - Puneet Utreja
- I. K. Gujral Punjab Technical University, Jalandhar-Punjab 144601, India
| | - Lalit Kumar
- I. K. Gujral Punjab Technical University, Jalandhar-Punjab 144601, India
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Mullins BT, Mazur L, Dance M, McGurk R, Schreiber E, Marks LB, Shen CJ, Lawrence MV, Chera BS. Common Error Pathways in CyberKnife™ Radiation Therapy. Front Oncol 2020; 10:1077. [PMID: 32733802 PMCID: PMC7360810 DOI: 10.3389/fonc.2020.01077] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2020] [Accepted: 05/29/2020] [Indexed: 12/02/2022] Open
Abstract
Purpose/Objectives: Stereotactic radiosurgery (SRS) and stereotactic body radiation therapy (SBRT) may be considered “high risk” due to the high doses per fraction. We analyzed CyberKnife™ (CK) SRS and SBRT-related incidents that were prospectively reported to our in-house incident learning system (ILS) in order to identify severity, contributing factors, and common error pathways. Material and Methods: From 2012 to 2019, 221 reported incidents related to the 4,569 CK fractions delivered (5.8%) were prospectively analyzed by our multi-professional Quality and Safety Committee with regard to severity, contributing factors, as well as the location where the incident occurred (tripped), where it was discovered (caught), and the safety barriers that were traversed (crossed) on the CK process map. Based on the particular step in the process map that incidents tripped, we categorized incidents into general error pathways. Results: There were 205 severity grade 1–2 (did not reach patient or no clinical impact), 11 grade 3 (clinical impact unlikely), 5 grade 4 (altered the intended treatment), and 0 grade 5–6 (life-threatening or death) incidents, with human performance being the most common contributing factor (79% of incidents). Incidents most commonly tripped near the time when the practitioner requested CK simulation (e.g., pre-CK simulation fiducial marker placement) and most commonly caught during the physics pre-treatment checklist. The four general error pathways included pre-authorization, billing, and scheduling issues (n= 119); plan quality (n= 30); administration of IV contrast during simulation or pre-medications during treatment (n= 22); and image guidance (n= 12). Conclusion: Most CK incidents led to little or no patient harm and most were related to billing and scheduling issues. Suboptimal human performance appeared to be the most common contributing factor to CK incidents. Additional study is warranted to develop and share best practices to reduce incidents to further improve patient safety.
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Affiliation(s)
- Brandon T Mullins
- Department of Radiation Oncology, University of North Carolina Hospitals, Chapel Hill, NC, United States
| | - Lukasz Mazur
- Division of Healthcare Engineering, Department of Radiation Oncology, University of North Carolina School of Medicine, Chapel Hill, NC, United States.,Carolina Health Informatics Program, School of Information and Library Science, University of North Carolina, Chapel Hill, NC, United States
| | - Michael Dance
- Department of Radiation Oncology, University of North Carolina Hospitals, Chapel Hill, NC, United States
| | - Ross McGurk
- Department of Radiation Oncology, University of North Carolina Hospitals, Chapel Hill, NC, United States
| | - Eric Schreiber
- Department of Radiation Oncology, University of North Carolina Hospitals, Chapel Hill, NC, United States
| | - Lawrence B Marks
- Department of Radiation Oncology, University of North Carolina Hospitals, Chapel Hill, NC, United States
| | - Colette J Shen
- Department of Radiation Oncology, University of North Carolina Hospitals, Chapel Hill, NC, United States
| | - Michael V Lawrence
- Department of Radiation Oncology, University of North Carolina Hospitals, Chapel Hill, NC, United States
| | - Bhishamjit S Chera
- Department of Radiation Oncology, University of North Carolina Hospitals, Chapel Hill, NC, United States
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Kareliotis G, Tremi I, Kaitatzi M, Drakaki E, Serafetinides AA, Makropoulou M, Georgakilas AG. Combined radiation strategies for novel and enhanced cancer treatment. Int J Radiat Biol 2020; 96:1087-1103. [PMID: 32602416 DOI: 10.1080/09553002.2020.1787544] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Numerous studies focus on cancer therapy worldwide, and although many advances have been recorded, the complexity of the disease dictates thinking out of the box to confront it. This study reviews some of the currently available ionizing (IR) and non-ionizing radiation (NIR)-based treatment methods and explores their possible combinations that lead to synergistic, multimodal approaches with promising therapeutic outcomes. Traditional techniques, like radiotherapy (RT) show decent results, although they cannot spare 100% the healthy tissues neighboring with the cancer ones. Targeted therapies, such as proton and photodynamic therapy (PT and PDT, respectively) present adequate outcomes, even though each one has its own drawbacks. To overcome these limitations, the combination of therapeutic modalities has been proposed and has already been showing promising results. At the same time, the recent advances in nanotechnology in the form of nanoparticles enhance cancer therapy, making multimodal treatments worthy of exploring and studying. The combination of RT and PDT has reached the level of clinical trials and is showing promising results. Moreover, in vitro and in vivo studies of nanoparticles with PDT have also provided beneficial results concerning enhanced radiation treatments. In any case, novel and multimodal approaches have to be adopted to achieve personalized, enhanced and effective cancer treatment.
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Affiliation(s)
- Georgios Kareliotis
- Department of Physics, School of Applied Mathematical and Physical Sciences, National Technical University of Athens (NTUA), Athens, Greece
| | - Ioanna Tremi
- Department of Physics, School of Applied Mathematical and Physical Sciences, National Technical University of Athens (NTUA), Athens, Greece
| | - Myrsini Kaitatzi
- Department of Physics, School of Applied Mathematical and Physical Sciences, National Technical University of Athens (NTUA), Athens, Greece
| | - Eleni Drakaki
- Department of Physics, School of Applied Mathematical and Physical Sciences, National Technical University of Athens (NTUA), Athens, Greece
| | - Alexandros A Serafetinides
- Department of Physics, School of Applied Mathematical and Physical Sciences, National Technical University of Athens (NTUA), Athens, Greece
| | - Mersini Makropoulou
- Department of Physics, School of Applied Mathematical and Physical Sciences, National Technical University of Athens (NTUA), Athens, Greece
| | - Alexandros G Georgakilas
- Department of Physics, School of Applied Mathematical and Physical Sciences, National Technical University of Athens (NTUA), Athens, Greece
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Abstract
Brain metastases are a very common manifestation of cancer that have historically been approached as a single disease entity given the uniform association with poor clinical outcomes. Fortunately, our understanding of the biology and molecular underpinnings of brain metastases has greatly improved, resulting in more sophisticated prognostic models and multiple patient-related and disease-specific treatment paradigms. In addition, the therapeutic armamentarium has expanded from whole-brain radiotherapy and surgery to include stereotactic radiosurgery, targeted therapies and immunotherapies, which are often used sequentially or in combination. Advances in neuroimaging have provided additional opportunities to accurately screen for intracranial disease at initial cancer diagnosis, target intracranial lesions with precision during treatment and help differentiate the effects of treatment from disease progression by incorporating functional imaging. Given the numerous available treatment options for patients with brain metastases, a multidisciplinary approach is strongly recommended to personalize the treatment of each patient in an effort to improve the therapeutic ratio. Given the ongoing controversies regarding the optimal sequencing of the available and expanding treatment options for patients with brain metastases, enrolment in clinical trials is essential to advance our understanding of this complex and common disease. In this Review, we describe the key features of diagnosis, risk stratification and modern paradigms in the treatment and management of patients with brain metastases and provide speculation on future research directions.
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Wei C, Qian P, Tedrow U, Mak R, Zei PC. Non-invasive Stereotactic Radioablation: A New Option for the Treatment of Ventricular Arrhythmias. Arrhythm Electrophysiol Rev 2020; 8:285-293. [PMID: 32685159 PMCID: PMC7358955 DOI: 10.15420/aer.2019.04] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023] Open
Abstract
Ventricular tachycardia (VT) is associated with significant morbidity and mortality. Radiofrequency catheter ablation can be effective for the treatment of VT but it carries a high rate of recurrence often attributable to insufficient depth of penetration for reaching critical arrhythmogenic substrates. Stereotactic body radioablation (SBRT) is a commonly used technology developed for the non-invasive treatment of solid tumours. Recent evidence suggests that it can also be effective for the treatment of VT. It is a non-invasive procedure and it has the unique advantage of delivering ablative energy to any desired volume within the body to reach sites that are inaccessible with catheter ablation. This article summarises the pre-clinical studies that have formed the evidence base for SBRT in the heart, describes the clinical approaches for SBRT VT ablation and provides perspective on next steps for this new treatment modality.
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Affiliation(s)
- Chen Wei
- Harvard Medical School, Boston, MA, US.,Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA, US
| | - Pierre Qian
- Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA, US
| | - Usha Tedrow
- Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA, US
| | - Raymond Mak
- Department of Radiation Oncology, Brigham and Women's Hospital/Dana-Farber Cancer Institute, Boston, MA, US
| | - Paul C Zei
- Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA, US
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Verhaak E, Gehring K, Hanssens PEJ, Aaronson NK, Sitskoorn MM. Health-related quality of life in adult patients with brain metastases after stereotactic radiosurgery: a systematic, narrative review. Support Care Cancer 2020; 28:473-484. [PMID: 31792879 PMCID: PMC6954134 DOI: 10.1007/s00520-019-05136-x] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2019] [Accepted: 10/16/2019] [Indexed: 01/03/2023]
Abstract
PURPOSE A growing number of patients with brain metastases (BM) are being treated with stereotactic radiosurgery (SRS), and the importance of evaluating the impact of SRS on the health-related quality of life (HRQoL) in these patients has been increasingly acknowledged. This systematic review summarizes the current knowledge about the HRQoL of patients with BM after SRS. METHODS We searched EMBASE, Medline Ovid, Web-of-Science, the Cochrane Database, PsycINFO Ovid, and Google Scholar up to November 15, 2018. Studies in patients with BM in which HRQoL was assessed before and after SRS and analyzed over time were included. Studies including populations of several types of brain cancer and/or several types of treatments were included if the results for patients with BM and treatment with SRS alone were described separately. RESULTS Out of 3638 published articles, 9 studies met the eligibility criteria and were included. In 4 out of 7 studies on group results, overall HRQoL of patients with BM remained stable after SRS. In small study samples of longer-term survivors, overall HRQoL remained stable up to 12 months post-SRS. Contradictory results were reported for physical and general/global HRQoL, which might be explained by the different questionnaires that were used. CONCLUSIONS In general, SRS does not have significant negative effects on patients' overall HRQoL over time. Future research is needed to analyze different aspects of HRQoL, differences in individual changes in HRQoL after SRS, and factors that influence these changes. These studies should take into account several methodological issues as discussed in this review.
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Affiliation(s)
- Eline Verhaak
- Gamma Knife Center, Elisabeth-TweeSteden Hospital, Hilvarenbeekseweg 60, 5022 GC, Tilburg, The Netherlands
- Department of Neurosurgery, Elisabeth-TweeSteden Hospital, Hilvarenbeekseweg 60, 5022 GC, Tilburg, The Netherlands
- Department of Cognitive Neuropsychology, Tilburg University, Warandelaan 2, 5037 AB, Tilburg, The Netherlands
| | - Karin Gehring
- Department of Neurosurgery, Elisabeth-TweeSteden Hospital, Hilvarenbeekseweg 60, 5022 GC, Tilburg, The Netherlands.
- Department of Cognitive Neuropsychology, Tilburg University, Warandelaan 2, 5037 AB, Tilburg, The Netherlands.
| | - Patrick E J Hanssens
- Gamma Knife Center, Elisabeth-TweeSteden Hospital, Hilvarenbeekseweg 60, 5022 GC, Tilburg, The Netherlands
- Department of Neurosurgery, Elisabeth-TweeSteden Hospital, Hilvarenbeekseweg 60, 5022 GC, Tilburg, The Netherlands
| | - Neil K Aaronson
- Division of Psychosocial Research and Epidemiology, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands
| | - Margriet M Sitskoorn
- Department of Neurosurgery, Elisabeth-TweeSteden Hospital, Hilvarenbeekseweg 60, 5022 GC, Tilburg, The Netherlands
- Department of Cognitive Neuropsychology, Tilburg University, Warandelaan 2, 5037 AB, Tilburg, The Netherlands
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Guo T, Ni J, Yang X, Li Y, Li Y, Zou L, Wang S, Liu Q, Chu L, Chu X, Li S, Ye L, Zhu Z. Pattern of Recurrence Analysis in Metastatic EGFR-Mutant NSCLC Treated with Osimertinib: Implications for Consolidative Stereotactic Body Radiation Therapy. Int J Radiat Oncol Biol Phys 2020; 107:62-71. [PMID: 31987959 DOI: 10.1016/j.ijrobp.2019.12.042] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2019] [Revised: 12/07/2019] [Accepted: 12/21/2019] [Indexed: 11/28/2022]
Abstract
PURPOSE Despite the impressive response rate to osimertinib, acquired resistance remains an obstacle to achieving long-term tumor control in metastatic epidermal growth factor receptor-mutant non-small cell lung cancer. Stereotactic body radiation therapy (SBRT) plays a growing role in the management of oligometastatic disease. We investigated the patterns of residual disease and progression on osimertinib, as well as the predictors of candidates for consolidative SBRT. METHODS AND MATERIALS The serial scans of patients with metastatic epidermal growth factor receptor-mutant non-small cell lung cancer treated with osimertinib were retrospectively reviewed. Disease progression in residual sites, new sites, and both residual and new sites were classified as residual-site recurrence (RR), new-site recurrence (NR), and combined RR and NR (RNR), respectively. Logistic regression analysis was performed to identify predictors of candidates for consolidative SBRT. RESULTS Ninety-seven patients were enrolled. The median time to maximal osimertinib response was 2.6 months. Twenty-six patients (26.8%) with oligoresidual disease were identified as candidates for consolidative SBRT at time of maximal response. Stage T1-2 before initiation of osimertinib (P = .046) was the independent predictor of consolidative SBRT eligibility. During a median follow-up of 10.9 months, disease progression was documented in 50 (51.5%) patients, and 70% of them experienced oligoprogression. Twenty-five (50%) patients developed disease progression in originally involved sites, 11 (22%) had new metastases, and 14 (28%) experienced disease progression in both original and new metastatic sites. Forty-six patients had progressive disease after experiencing initial stable disease or objective response to osimertinib. RR occurred in 20 (43.5%) of these patients, NR in 14 (30.4%), and RNR in 12 (26.1%). Notably, within the subgroup of patients eligible for consolidative SBRT, RR was observed in 6 (54.5%) patients, RNR in 3 (27.3%), and NR in 2 (18.2%). CONCLUSIONS The majority of progressive disease on osimertinib was within residual lesions in initially involved sites. Consolidative SBRT may prolong time to progression in a selected subgroup of patients, which merits further investigation.
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Affiliation(s)
- Tiantian Guo
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Jianjiao Ni
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Xi Yang
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Yuan Li
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China; Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Yida Li
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Liqing Zou
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Shengping Wang
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China; Department of Radiology, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Quan Liu
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China; Department of Radiology, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Li Chu
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Xiao Chu
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Shuyan Li
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Luxi Ye
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Zhengfei Zhu
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
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Yang SH, Kim HY, Lee SI, Jin SJ. The Effect of Epidermal Growth Factor Receptor Mutation on Intracranial Progression-Free Survival of Non-Small Cell Lung Cancer Patients with Brain Metastasis Underwent Gamma Knife Radiosurgery. Brain Tumor Res Treat 2020; 8:103-108. [PMID: 33118342 PMCID: PMC7595855 DOI: 10.14791/btrt.2020.8.e15] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2020] [Revised: 05/22/2020] [Accepted: 07/14/2020] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND The aim of this study was to survey prognostic factors, particularly those focusing on epidermal growth factor receptor (EGFR) mutations, of patients with non-small cell lung cancer (NSCLC) after Gamma Knife Radiosurgery (GKRS) for metastatic brain tumors. METHODS We retrospectively reviewed the medical records of 98 patients with NSCLC who underwent GKRS for brain metastases from August 2010 to July 2017. The primary endpoint was progression-free survival (PFS) of the intracranial disease. We analyzed variables such as age, sex, Karnofsky Performance Status, recursive partitioning analysis (RPA) class, smoking status, primary cancer pathology, EGFR mutations, and time to brain metastases as prognostic factors. RESULTS The median overall survival (OS) of the patients was 16 months [95% confidence interval (CI), 13-21 months]. Median systemic PFS and intracranial PFS were 9 months (95% CI, 8-11 months) and 11 months (95% CI, 7-14 months), respectively. Kaplan-Meier survival analysis revealed that the patients with EGFR mutations had longer intracranial PFS than those without EGFR mutation (median intracranial PFS: 19 vs. 10 months with p=0.01) while they had no benefits in OS and systemic PFS. Furthermore, the patients harboring adenocarcinoma had longer OS (p<0.01) and intracranial PFS (p<0.01) and the patients with lower RPA class had longer OS (p=0.02) and intracranial PFS (p=0.03). CONCLUSION EGFR mutations, primary cancer pathology, and RPA class may be proposed as prognostic factors for intracranial PFS in NSCLC patients after GKRS for brain metastasis in this study.
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Affiliation(s)
- Seung Hyeon Yang
- Department of Neurosurgery, Haeundae Paik Hospital, Inje University College of Medicine, Busan, Korea
| | - Hae Yu Kim
- Department of Neurosurgery, Haeundae Paik Hospital, Inje University College of Medicine, Busan, Korea.,Department of Neurosurgery, Gamma Knife Center, Haeundae Paik Hospital, Inje University College of Medicine, Busan, Korea.
| | - Sun Il Lee
- Department of Neurosurgery, Haeundae Paik Hospital, Inje University College of Medicine, Busan, Korea.,Department of Neurosurgery, Gamma Knife Center, Haeundae Paik Hospital, Inje University College of Medicine, Busan, Korea
| | - Seong Jin Jin
- Department of Neurosurgery, Gamma Knife Center, Haeundae Paik Hospital, Inje University College of Medicine, Busan, Korea
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The Choice of Local Treatment Modalities for Patients with Brain Metastases from Digestive Cancers. JOURNAL OF ONCOLOGY 2019; 2019:1568465. [PMID: 31871456 PMCID: PMC6907058 DOI: 10.1155/2019/1568465] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/11/2019] [Accepted: 09/13/2019] [Indexed: 11/17/2022]
Abstract
Background Brain metastases (BMs) from digestive cancers are rare; therefore, no optimal treatment modality has been defined. Methods We retrospectively reviewed the clinical data of 68257 patients with digestive cancers. Propensity score matching (PSM) was used to balance patient backgrounds between groups. Survival differences between different treatment modalities were compared. Univariate and multivariate Cox proportional hazards models were performed to identify prognostic factors on overall survival (OS). Results 270 patients with BM entered the study. In the entire group, the median survival time after diagnosis of brain metastases was 10.25 months (95% CI: 8.41–12.09 months); local treatment could significantly prolong OS (respectively, P < 0.01; even after PSM, P < 0.01); combination treatment was more effective than single treatment modality (respectively, P < 0.01; even after PSM, P < 0.01). However, each combination modality was identically effective (P > 0.05). When patients were divided into three groups based on 1, 2-3, or more than 3 metastatic lesion(s), same results were identified between local treatment and without local treatment (1 lesion, P < 0.01; 2-3 lesions, P < 0.01; more than 3 lesions, P < 0.01, respectively) and combination and single treatment (P < 0.01, P=0.02, P=0.03, respectively). However, there was no difference between different combined treatments (P > 0.05). Multivariate analysis revealed that performance status (P < 0.01), presence of extracranial metastasis (P=0.04), number of BM (P < 0.01), and local treatment for BM (P < 0.01) were independent prognostic factors. Conclusions Regardless of the number of brain lesions, local treatment achieved higher overall survival times than no local treatment, and combination therapy could offer survival benefit to patients as compared with single therapy.
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MRI appearance change during stereotactic radiotherapy for large brain metastases and importance of treatment plan modification during treatment period. Jpn J Radiol 2019; 37:850-859. [PMID: 31617151 PMCID: PMC6874519 DOI: 10.1007/s11604-019-00886-4] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2019] [Accepted: 10/06/2019] [Indexed: 12/31/2022]
Abstract
Purpose We aimed to evaluate the magnetic resonance imaging (MRI) appearance changes during stereotactic radiotherapy (SRT) for large sized brain metastases, and analyze the lesions necessitating treatment plan modification. Materials and methods A total of 23 patients (27 lesions, >2 cm in tumor diameter) underwent SRT and all lesions were evaluated the appearance changes which had the necessity of the treatment plan modification. The appearance change of tumor during SRT was evaluated using gadolinium-enhanced MRI. The reasons of the modification were classified into tumor reduction, tumor enlargement, displacement, and shape change. Results Among the 27 lesions, 55.6% required the treatment plan modification. The reasons were tumor reduction in six lesions, tumor enlargement in three lesions, displacement in three lesions, and shape change in three lesions. The planning target volume (PTV) size changed up to 43.0% and the shift of center of PTV was a maximum of 1.7 mm. The pathological status (adenocarcinoma vs others) and timing of steroid administration (prior vs after SRT start) were the predictive factors of tumor changes required the modification. Conclusions As tumor changes might occur even during short period of SRT, the treatment plan evaluation and modification were important in SRT for large brain metastases.
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Bauknecht HC, Klingebiel R, Hein P, Wolf C, Bornemann L, Siebert E, Bohner G. Effect of MRI-based semiautomatic size-assessment in cerebral metastases on the RANO-BM classification. Clin Neuroradiol 2019; 30:263-270. [PMID: 31197388 DOI: 10.1007/s00062-019-00785-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2018] [Accepted: 04/15/2019] [Indexed: 11/29/2022]
Abstract
AIM Evaluation of a semiautomatic software algorithm for magnetic resonance imaging (MRI)-based assessment of cerebral metastases in cancer patients. MATERIAL AND METHODS Brain metastases (n = 131) in 38 patients, assessed by contrast-enhanced MRI, were retrospectively evaluated at two timepoints (baseline, follow-up) by two experienced neuroradiologists in a blinded manner. The response assessment in neuro-oncology (RANO) criteria for brain metastases (RANO-BM) were applied by means of a software (autoRANO-BM) as well as manually (manRANO-BM) at an interval of 3 weeks. RESULTS The average diameter of metastases was 12.03 mm (SD ± 6.66 mm) for manRANO-BM and 13.97 mm (SD ± 7.76 mm) for autoRANO-BM. Diameter figures were higher when using semiautomatic measurements (median = 11.8 mm) as compared to the manual ones (median = 10.2 mm; p = 0.000). Correlation coefficients for intra-observer variability were 0.993 (autoRANO-BM) and 0.979 (manRANO-BM). The interobserver variability (R1/R2) was 0.936/0.965 for manRANO-BM and 0.989/0.998 for autoRANO-BM. A total of 19 lesions (15%) were classified differently when using semiautomatic measurements. In 14 cases with suspected disease progression by manRANO-BM a stable course was found according to autoRANO-BM. CONCLUSION Computerized measuring techniques can aid in the assessment of cerebral metastases by reducing examiner-dependent effects and may consequently result in a different classification according to RANO-BM criteria.
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Affiliation(s)
- Hans-Christian Bauknecht
- Department of Neuroradiology, Charité-University Medicine Berlin, Charitéplatz 1, 10117, Berlin, Germany.
| | - Randolf Klingebiel
- Department of diagnostic and interventional Neuroradiology, Protestant Hospital Bethel, Burgsteig 1, 33617, Bielefeld, Germany
| | - Patrick Hein
- , Practice at Prinzregentenplatz 13, 81675, Munich, Germany
| | - Claudia Wolf
- Pediatric practice in the medical center, Adlerstr. 48, 14612, Falkensee, Germany
| | - Lars Bornemann
- Fraunhofer Institute for Medical Image Computing MeVis, Am Fallturm 1, 28359, Bremen, Germany
| | - Eberhard Siebert
- Department of Neuroradiology, Charité-University Medicine Berlin, Charitéplatz 1, 10117, Berlin, Germany
| | - Georg Bohner
- Department of Neuroradiology, Charité-University Medicine Berlin, Charitéplatz 1, 10117, Berlin, Germany
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Nivet A, Schlienger M, Clavère P, Huguet F. Effets de l’irradiation à haute dose sur la vascularisation : physiopathologie et conséquences cliniques. Cancer Radiother 2019; 23:161-167. [DOI: 10.1016/j.canrad.2018.05.009] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2018] [Revised: 05/04/2018] [Accepted: 05/10/2018] [Indexed: 11/16/2022]
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Ni J, Li G, Yang X, Chu L, Wang J, Li Y, Zou L, Li Y, Xie C, Zhu Z. Optimal timing and clinical value of radiotherapy in advanced ALK-rearranged non-small cell lung cancer with or without baseline brain metastases: implications from pattern of failure analyses. Radiat Oncol 2019; 14:44. [PMID: 30866974 PMCID: PMC6417092 DOI: 10.1186/s13014-019-1240-1] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2018] [Accepted: 02/18/2019] [Indexed: 01/20/2023] Open
Abstract
Background Despite development of several next-generation tyrosine kinase inhibitors (TKIs), crizotinib remains one of the first-line treatment options for advanced ALK-positive NSCLC and is widely used in situations where next-generation TKIs aren’t yet approved or economically inaccessible. However, the pattern of failure and clinical value of radiotherapy in metastatic crizotinib-treated ALK-mutant lung cancer, with or without baseline brain metastases (BBM), are largely unknown. Methods Consecutive crizotinib-treated NSCLC patients with adequate imaging and measurable disease were retrospectively enrolled. Disease progression in original sites (primary/metastatic), new sites, or both, are classified as original failure (OF), distant failure (DF) and ODF, respectively. Progression free survival, from crizotinib initiation to the first disease progression, and from that to the second disease progression, were calculated as PFS1 and PFS2. Results Ninety-three patients were identified. With a median follow up of 22.0 (range, 2.0–72.0) months, 52 patients had crizotinib-treatment failure. The frequencies of OF, ODF, and DF, were 50.0, 26.9, and 23.1%, respectively. Histology, primary tumor size and presence of BBM, were independently associated with OF, using competing risks analyses. The brain was the most common site of initial disease progression. Patients with BBM had a significant higher possibility developing multiple-progressive lesions in the brain (p = 0.002). Importantly, four of the ten patients who had baseline oligo-metastatic cranial disease but didn’t receive upfront brain radiation, developed multiple-progressive disease in the brain. Brain radiation before crizotinib could alter the disease failure patterns and improve PFS1 among patients with BBM (p = 0.006). Extracranial radiation was efficient in controlling symptoms but it was not associated with PFS1 (p = 0.223), and the majority of patients were eligible for salvage radiotherapy upon disease progression to crizotinib. By the time of data cut-off, 28 patients had second disease progression, with a median PFS2 of 7.0 (95% CI 5.4–8.6) months and salvage radiotherapy significantly prolonged PFS2 (p = 0.003). Additionally, patients receiving any radiotherapy during their treatment course had a significant longer overall survival (p = 0.048). Conclusions Among patients with baseline oligo-metastatic brain lesions which are suitable for stereotactic radiosurgery, upfront brain radiotherapy provides considerable clinical benefits. While, extracranial radiation may be deferred in asymptomatic patients with multiple-metastatic lesions. Electronic supplementary material The online version of this article (10.1186/s13014-019-1240-1) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Jianjiao Ni
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, 270 Dong An Road, Shanghai, 200032, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
| | - Guodong Li
- Department of Interventional Radiology, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
| | - Xi Yang
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, 270 Dong An Road, Shanghai, 200032, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
| | - Li Chu
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, 270 Dong An Road, Shanghai, 200032, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
| | - Jialei Wang
- Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
| | - Yida Li
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, 270 Dong An Road, Shanghai, 200032, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
| | - Liqing Zou
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, 270 Dong An Road, Shanghai, 200032, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
| | - Yuan Li
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
| | - Congying Xie
- Radiotherapy and Chemotherapy Department, the 1st Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Zhengfei Zhu
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, 270 Dong An Road, Shanghai, 200032, China. .,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
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Kim KH, Lee MH, Cho KR, Choi JW, Kong DS, Seol HJ, Nam DH, Lee JI. The influence of histology on the response of brain metastases to gamma knife radiosurgery: a propensity score-matched study. Acta Neurochir (Wien) 2018; 160:2379-2386. [PMID: 30413940 DOI: 10.1007/s00701-018-3726-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2018] [Accepted: 11/01/2018] [Indexed: 10/27/2022]
Abstract
BACKGROUND In terms of response to fractionated radiotherapy, metastatic brain tumors of certain origins are considered radioresistant. OBJECTIVE To determine the influence of "radioresistant" histology on outcomes of brain metastases treated with radiosurgery. METHODS Between 2001 and 2017, 121 patients with brain metastases from renal cell carcinoma (RCC) and 2151 from non-small cell lung cancer (NSCLC) were reviewed. Eighty-seven pairs were derived using propensity score matching. Local progression-free survival (PFS), progression patterns, distant PFS, and overall survival were investigated. RESULTS The median follow-up period was 13.7 months (range, 1.6-78.4 months). A total of 536 lesions were treated using gamma knife radiosurgery (GKS), with a median dose of 20 Gy (range, 12-28 Gy). The actuarial local PFS rates in the RCC group were 91% and 89% at 6 and 12 months, respectively, and did not differ from the NSCLC group (97% and 83% at 6 and 12 months, respectively). Continuous progression, without response to GKS, was noted in seven of the eight progressed RCCs. However, six of the seven progressed NSCLCs showed transient shrinkage before progression. The median distant PFS was 9.3 months (95% CI, 6.3-12.2) in the RCC group and 8.0 months (95% CI, 5.5-10.4) in the NSCLC group. The median overall survival was 16.1 months (95% CI, 11.3-20.8) and 14.9 months (95% CI, 11.9-17.8) in RCC and NSCLC groups, respectively. CONCLUSION Histological differences had no effect on local control in the single high-dose range used for radiosurgery. However, changes in tumor volume during progression varied across tumor histology.
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Affiliation(s)
- Kyung Hwan Kim
- Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, South Korea
| | - Min Ho Lee
- Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, South Korea
| | - Kyung-Rae Cho
- Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, South Korea
| | - Jung-Won Choi
- Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, South Korea
| | - Doo-Sik Kong
- Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, South Korea
| | - Ho Jun Seol
- Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, South Korea
| | - Do-Hyun Nam
- Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, South Korea
| | - Jung-Il Lee
- Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, South Korea.
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Garcia MA, Anwar M, Yu Y, Duriseti S, Merritt B, Nakamura J, Hess C, Theodosopoulos PV, McDermott M, Sneed PK, Braunstein SE. Brain metastasis growth on preradiosurgical magnetic resonance imaging. Pract Radiat Oncol 2018; 8:e369-e376. [DOI: 10.1016/j.prro.2018.06.004] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2018] [Revised: 04/16/2018] [Accepted: 06/04/2018] [Indexed: 12/01/2022]
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Uto M, Mizowaki T, Ogura K, Mukumoto N, Katagiri T, Takehana K, Hiraoka M. Dosimetric comparison between dual-isocentric dynamic conformal arc therapy and mono-isocentric volumetric-modulated arc therapy for two large brain metastases. JOURNAL OF RADIATION RESEARCH 2018; 59:774-781. [PMID: 30102325 PMCID: PMC6251429 DOI: 10.1093/jrr/rry064] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/19/2018] [Revised: 05/02/2018] [Indexed: 06/08/2023]
Abstract
Mono-isocentric volumetric-modulated arc therapy (VMAT) can be used to treat multiple brain metastases. It remains unknown whether mono-isocentric VMAT can improve the dose distribution compared with dual-isocentric dynamic conformal arc therapy (DCAT), especially for two brain metastases. We compared the dose distribution between dual-isocentric DCAT and mono-isocentric VMAT for two large brain metastases, and analyzed the relationship between the distance between the two targets and the difference in dose distribution. A total of 19 patients, each with two large brain metastases, were enrolled. The dose prescribed for each planning target volume (PTV) was 28 Gy in five fractions (D99.8 = 100%). We created new indices derived from conformity indices suggested by the Radiation Therapy Oncology Group (RTOG; mRTOG-CI) and Paddick et al. (mIP-CI), using the dosimetric parameters of the sum of the two PTVs. The median PTV was 5.05 cm3 (range, 2.10-28.47). VMAT significantly improved mRTOG-CI and mIP-CI compared with DCAT. In all cases, VMAT was able to improve mRTOG-CI and mIP-CI compared with DCAT. Whereas the normal brain volume receiving 5 Gy was similar between the two modalities, the normal brain receiving 10, 12, 15, 20, 25 and 28 Gy (V10-V28) was significantly smaller in VMAT. The mean beam-on times were 213.3 s and 121.9 s in DCAT and VMAT, respectively (P < 0.001). Mono-isocentric VMAT improved the target conformity and reduced the beam-on time and V10-V28 of the normal brain for not only two close metastases but also two distant metastases. Mono-isocentric VMAT seems to be a promising treatment technique for two large brain metastases.
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Affiliation(s)
- Megumi Uto
- Department of Radiation Oncology and Image-applied Therapy, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, Japan
| | - Takashi Mizowaki
- Department of Radiation Oncology and Image-applied Therapy, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, Japan
| | - Kengo Ogura
- Department of Radiation Oncology and Image-applied Therapy, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, Japan
| | - Nobutaka Mukumoto
- Department of Radiation Oncology and Image-applied Therapy, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, Japan
| | - Tomohiro Katagiri
- Department of Radiation Oncology and Image-applied Therapy, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, Japan
| | - Keiichi Takehana
- Department of Radiation Oncology and Image-applied Therapy, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, Japan
| | - Masahiro Hiraoka
- Department of Radiation Oncology and Image-applied Therapy, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, Japan
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Stewart CL, Warner S, Ito K, Raoof M, Wu GX, Kessler J, Kim JY, Fong Y. Cytoreduction for colorectal metastases: liver, lung, peritoneum, lymph nodes, bone, brain. When does it palliate, prolong survival, and potentially cure? Curr Probl Surg 2018; 55:330-379. [PMID: 30526930 DOI: 10.1067/j.cpsurg.2018.08.004] [Citation(s) in RCA: 147] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2018] [Accepted: 08/28/2018] [Indexed: 12/19/2022]
Affiliation(s)
- Camille L Stewart
- Division of Surgical Oncology, City of Hope National Medical Center, Duarte, CA
| | - Susanne Warner
- Division of Surgical Oncology, City of Hope National Medical Center, Duarte, CA
| | - Kaori Ito
- Department of Surgery, Michigan State University, Lansing, MI
| | - Mustafa Raoof
- Division of Surgical Oncology, City of Hope National Medical Center, Duarte, CA
| | - Geena X Wu
- Division of Thoracic Surgery, City of Hope National Medical Center, Duarte, CA
| | - Jonathan Kessler
- Department of Diagnostic Radiology, City of Hope National Medical Center, Duarte, CA
| | - Jae Y Kim
- Division of Thoracic Surgery, City of Hope National Medical Center, Duarte, CA
| | - Yuman Fong
- Division of Surgical Oncology, City of Hope National Medical Center, Duarte, CA.
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