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Rowbottom H, Končnik R, Ravnik J, Šmigoc T. Posterior Fossa Stereotactic Biopsy with Leksell Vantage Frame-Case Series and Review of Literature. J Clin Med 2025; 14:609. [PMID: 39860615 PMCID: PMC11766265 DOI: 10.3390/jcm14020609] [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: 10/27/2024] [Revised: 11/24/2024] [Accepted: 01/14/2025] [Indexed: 01/27/2025] Open
Abstract
Background: Stereotactic biopsy of posterior fossa lesions, which are often inoperable, enables a safe trajectory and provides tissue samples for accurate diagnosis, which is crucial for correct treatment since the latest World Health Organization Classification of Tumors of the Central Nervous System from 2021 places immense emphasis on molecular diagnostics. Stereotactic biopsy using the Leksell Vantage headframe is, due to its rigid design, extremely accurate, but stiffer, making the procedure more challenging and the learning curve steeper. Methods: This retrospective analysis demonstrates the introduction of the new Leksell Vantage headframe in day-to-day practice at the University Medical Center in Maribor, Slovenia, in demanding procedures of posterior fossa biopsies, and also provides a review of the literature available on the topic with emphasis on the technical aspect of posterior fossa biopsy using the Leksell Vantage headframe in adults. Results: In the observed series of three patients with posterior fossa lesions, all biopsies were representative, despite tissue samples being small, providing conclusive histopathologic reports (glioblastoma, rosette-forming glioneuronal tumor and metastasis of melanoma) with additional molecular diagnostics. After the initial biopsy case, the preoperative planning times and procedure times were shortened as we learnt about the importance of a tailored approach from the first case. In all cases, the biopsy was performed under local anesthesia with patients being awake throughout surgery. Conclusions: The rigid Leksell Vantage headframe makes access to the posterior fossa tougher when compared to its predecessors. However, the procedure is very accurate but requires precise preoperative planning and a customized approach when placing the headframe.
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Affiliation(s)
| | | | | | - Tomaž Šmigoc
- Department of Neurosurgery, University Medical Centre Maribor, 2000 Maribor, Slovenia; (H.R.); (J.R.)
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Tao W, Jiang C, Xie J, Liu W, Wang S, Zhang J, Qiao X, Yu J, Jia T, Cao Y. Whole-Brain Radiotherapy Simultaneous Integrated Boost Intensity-Modulated Radiotherapy Combined With Anlotinib in the Treatment of Brain Metastases. Cancer Control 2025; 32:10732748251319489. [PMID: 39951682 PMCID: PMC11829290 DOI: 10.1177/10732748251319489] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2024] [Revised: 01/09/2025] [Accepted: 01/22/2025] [Indexed: 02/16/2025] Open
Abstract
INTRODUCTION Whole-brain radiotherapy simultaneous integrated boost intensity-modulated radiotherapy (WBRT + SIB-IMRT) is a potential treatment approach for brain metastasis (BM) that may result in improved overall survival (OS). However, the safety and efficacy of WBRT + SIB-IMRT combined with anlotinib for BM treatment remain uncertain. METHODS We retrospectively compared the safety and efficacy of anlotinib + WBRT + SIB-IMRT with those of WBRT + SIB-IMRT in patients with BM from 2019 to 2022. The adverse reaction type and grade, intracranial objective response rate (iORR), intracranial disease control rate (iDCR), OS, and intracranial progression-free survival (iPFS) of anlotinib + WBRT + SIB-IMRT were compared with those of WBRT + SIB-IMRT alone. RESULTS In total, 63 patients received either anlotinib + WBRT + SIB-IMRT or WBRT + SIB-IMRT alone (n = 31 and 32, respectively). No significant clinical differences were found between the two groups. The iORR and iDCR were higher in the anlotinib + WBRT + SIB-IMRT group than in the WBRT + SIB-IMRT group. The median iPFS and median OS of the 31 patients who received anlotinib + WBRT + SIB-IMRT were 14.5 and 18.9 months, respectively, whereas the median iPFS and median OS for the 32 patients who received WBRT + SIB-IMRT alone were 11.4 and 14.9 months, respectively. Thus, anlotinib combined with WBRT + SIB-IMRT increased the duration of iPFS, but not OS. iPFS was influenced by the Karnofsky Performance Status (KPS) score, age, extracranial distant metastasis, and addition of anlotinib to treatment, whereas OS correlated with age, extracranial distant metastasis, and KPS score. No treatment-related adverse events of grade 3 or higher occurred in either group. CONCLUSIONS Anlotinib combined with WBRT + SIB-IMRT is effective for BM and is well tolerated by patients.
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Affiliation(s)
- Wei Tao
- Department of Radiation Oncology, Nanjing PuKou People’s Hospital, Nanjing, China
| | - Chunyu Jiang
- Department of Radiation Oncology, Nanjing PuKou People’s Hospital, Nanjing, China
| | - Jiaqi Xie
- Department of Oncology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Wei Liu
- Department of Oncology, Huaibei People’s Hospital, Huaibei, China
| | - Shuan Wang
- Department of Clinic Nutrition, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Jianyu Zhang
- Department of Radiation Oncology, Nanjing PuKou People’s Hospital, Nanjing, China
| | - Xue Qiao
- Department of Radiation Oncology, Nanjing PuKou People’s Hospital, Nanjing, China
| | - Jingyi Yu
- Department of Radiation Oncology, Nanjing PuKou People’s Hospital, Nanjing, China
| | - Ting Jia
- Department of Neurology, Nanjing PuKou People’s Hospital, Nanjing, China
| | - Yuandong Cao
- Department of Radiation Oncology, Nanjing Medical University First Affiliated Hospital, Nanjing, China
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Kitano Y, Ohyama S, Yagi Y, Onishi I, Kayahara M. Surgical resection of brain and adrenal gland metastases from gastric cancer: a case report and literature review. J Surg Case Rep 2024; 2024:rjae163. [PMID: 38524679 PMCID: PMC10958142 DOI: 10.1093/jscr/rjae163] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2024] [Accepted: 02/23/2024] [Indexed: 03/26/2024] Open
Abstract
The prognosis of recurrent gastric cancer is generally poor, and aggressive surgical treatment is rarely performed. Herein, we present the case of a patient who underwent resection of cerebellar and adrenal gland metastases from gastric cancer. The patient was treated for gastric cancer with distal gastrectomy at 23 years and for remnant gastric cancer with completion gastrectomy at 48 years. At 59 years old, she experienced vertigo and nausea and was diagnosed with cerebellar and left adrenal gland tumours. First, the cerebellar tumours were resected and diagnosed as metastases of gastric cancer. After 1 month, the adrenal gland tumour was resected and diagnosed as metastatic. She underwent whole-brain radiotherapy and subsequent chemotherapy with S-1. One year after the surgery, the patient died of meningitis carcinomatosa. There are few reports on long-term survival after the resection of brain metastases. Herein, we report our experience along with a review of the literature.
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Affiliation(s)
- Yuto Kitano
- Department of Surgery, National Hospital Organization Kanazawa Medical Center, Kanazawa 920-8650, Japan
| | - Shigekazu Ohyama
- Department of Surgery, National Hospital Organization Kanazawa Medical Center, Kanazawa 920-8650, Japan
| | - Yasumichi Yagi
- Department of Surgery, National Hospital Organization Kanazawa Medical Center, Kanazawa 920-8650, Japan
| | - Ichiro Onishi
- Department of Surgery, National Hospital Organization Kanazawa Medical Center, Kanazawa 920-8650, Japan
| | - Masato Kayahara
- Department of Surgery, National Hospital Organization Kanazawa Medical Center, Kanazawa 920-8650, Japan
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Haider G, Dadey DYA, Rodrigues A, Pollom EL, Adler JR, Veeravagu A. Socio-economic disparities influence likelihood of post-operative radiation to resection cavities of metastatic brain tumors. Acta Neurochir (Wien) 2023; 165:4253-4258. [PMID: 37816918 DOI: 10.1007/s00701-023-05826-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2023] [Accepted: 09/28/2023] [Indexed: 10/12/2023]
Abstract
PURPOSE Irradiating the surgical bed of resected brain metastases improves local and distant disease control. Over time, stereotactic radiosurgery (SRS) has replaced whole brain radiotherapy (WBRT) as the treatment standard of care because it minimizes long-term damage to neuro-cognition. Despite this data and growing adoption, socio-economic disparities in clinical access can result in sub-standard care for some patient populations. We aimed to analyze the clinical and socio-economic characteristics of patients who did not receive radiation after surgical resection of brain metastasis. METHODS Our sample was obtained from Clinformatics® Data Mart Database and included all patients from 2004 to 2021 who did or did not receive radiation treatment within sixty days after resection of tumors metastatic to the brain. Regression analysis was done to identify factors responsible for loss to adjuvant radiation treatment. RESULTS Of 8362 patients identified who had undergone craniotomy for resection of metastatic brain tumors, 3430 (41%) patients did not receive any radiation treatment. Compared to patients who did receive some form of radiation treatment (SRS or WBRT), patients who did not get any form of radiation were more likely to be older (p = 0.0189) and non-white (p = 0.008). Patients with Elixhauser Comorbidity Index ≥3 were less likely to receive radiation treatment (p < 0.01). Fewer patients with household income ≥ $75,000 did not receive radiation treatment (p < 0.01). CONCLUSION Age, race, household income, and comorbidity status were associated with differential likelihood to receive post-operative radiation treatment.
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Affiliation(s)
- Ghani Haider
- Department of Neurosurgery, Stanford University Medical Center, 453 Quarry Road, Stanford, CA, 94304, USA.
| | - David Y A Dadey
- Department of Neurosurgery, Stanford University Medical Center, 453 Quarry Road, Stanford, CA, 94304, USA
| | - Adrian Rodrigues
- School of Medicine, Stanford University, 291 Campus Drive, Stanford, CA, 94305, USA
| | - Erqi L Pollom
- Department of Radiation Oncology, Stanford University School of Medicine, 875 Blake Wilbur Drive, Stanford, CA, 94305, USA
| | - John R Adler
- Department of Neurosurgery, Stanford University Medical Center, 453 Quarry Road, Stanford, CA, 94304, USA
| | - Anand Veeravagu
- Department of Neurosurgery, Stanford University Medical Center, 453 Quarry Road, Stanford, CA, 94304, USA
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Schnurman Z, Mashiach E, Link KE, Donahue B, Sulman E, Silverman J, Golfinos JG, Oermann EK, Kondziolka D. Causes of Death in Patients With Brain Metastases. Neurosurgery 2023; 93:986-993. [PMID: 37255296 DOI: 10.1227/neu.0000000000002542] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2023] [Accepted: 04/04/2023] [Indexed: 06/01/2023] Open
Abstract
BACKGROUND AND OBJECTIVES Advances in targeted therapies and wider application of stereotactic radiosurgery (SRS) have redefined outcomes of patients with brain metastases. Under modern treatment paradigms, there remains limited characterization of which aspects of disease drive demise and in what frequencies. This study aims to characterize the primary causes of terminal decline and evaluate differences in underlying intracranial tumor dynamics in patients with metastatic brain cancer. These fundamental details may help guide management, patient counseling, and research priorities. METHODS Using NYUMets-Brain-the largest, longitudinal, real-world, open data set of patients with brain metastases-patients treated at New York University Langone Health between 2012 and 2021 with SRS were evaluated. A review of electronic health records allowed for the determination of a primary cause of death in patients who died during the study period. Causes were classified in mutually exclusive, but collectively exhaustive, categories. Multilevel models evaluated for differences in dynamics of intracranial tumors, including changes in volume and number. RESULTS Of 439 patients with end-of-life data, 73.1% died secondary to systemic disease, 10.3% died secondary to central nervous system (CNS) disease, and 16.6% died because of other causes. CNS deaths were driven by acute increases in intracranial pressure (11%), development of focal neurological deficits (18%), treatment-resistant seizures (11%), and global decline driven by increased intracranial tumor burden (60%). Rate of influx of new intracranial tumors was almost twice as high in patients who died compared with those who survived ( P < .001), but there was no difference in rates of volume change per intracranial tumor ( P = .95). CONCLUSION Most patients with brain metastases die secondary to systemic disease progression. For patients who die because of neurological disease, tumor dynamics and cause of death mechanisms indicate that the primary driver of decline for many may be unchecked systemic disease with unrelenting spread of new tumors to the CNS rather than failure of local growth control.
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Affiliation(s)
- Zane Schnurman
- Department of Neurosurgery, NYU Langone Health, New York , New York , USA
| | - Elad Mashiach
- Department of Neurosurgery, NYU Langone Health, New York , New York , USA
| | - Katherine E Link
- Department of Neurosurgery, NYU Langone Health, New York , New York , USA
| | - Bernadine Donahue
- Department of Radiation Oncology, NYU Langone Health, New York , New York , USA
| | - Erik Sulman
- Department of Radiation Oncology, NYU Langone Health, New York , New York , USA
| | - Joshua Silverman
- Department of Radiation Oncology, NYU Langone Health, New York , New York , USA
| | - John G Golfinos
- Department of Neurosurgery, NYU Langone Health, New York , New York , USA
| | - Eric Karl Oermann
- Department of Neurosurgery, NYU Langone Health, New York , New York , USA
| | - Douglas Kondziolka
- Department of Neurosurgery, NYU Langone Health, New York , New York , USA
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Maarif R, Kubota Y, Chernov MF. Early tumor-related hemorrhage after stereotactic radiosurgery of brain metastases: Systematic review of reported cases. J Clin Neurosci 2023; 115:66-70. [PMID: 37499321 DOI: 10.1016/j.jocn.2023.07.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2023] [Revised: 06/20/2023] [Accepted: 07/07/2023] [Indexed: 07/29/2023]
Abstract
OBJECTIVE Early (within 72 h) tumor-related hemorrhage (TRH) after stereotactic radiosurgery (SRS) of brain metastases (BM) has been reported only occasionally. Systematic review of such cases was done. METHODS Literature search was performed through PubMed according to PRISMA guidelines using combination of the following medical subject headings: "hemorrhage," "stereotactic radiosurgery," and "brain metastasis." RESULTS In total, 7 case reports and 8 clinical series, which noted early TRH after SRS of BM were identified. Scarce and inconsistent data precluded their precise synthesis and statistical analysis. BM of renal cell carcinoma comprised around one-third of reported cases. In 4 patients with multiple BM, TRH after SRS was noted simultaneously in several irradiated tumors. Considering 17 reported cases overall, in 3 patients TRH occurred during SRS session itself, in 4 within several minutes upon completion of treatment, in 7 within several hours thereafter, and in 3 on the third posttreatment day. Out of 11 reported cases providing detailed outcome, 6 patients died shortly after the ictus, 2 others were severely disabled at discharge, and 3 demonstrated good-to-moderate recovery. Overall, among evaluated series the median rates of early TRH after SRS for BM were 0.8% per patient (range, 0.4 - 1.9%) and 0.3% per tumor (range, 0.05 - 0.8%). CONCLUSION Early TRH is very rare, but potentially life-threatening complication of SRS for BM; thus, its risk (while extremely low) and possible consequences should be discussed at the time of obtaining informed consent.
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Affiliation(s)
- Raisul Maarif
- Dr. Soetomo General Hospital and Airlangga University, Surabaya, Indonesia; Department of Neurosurgery, Tokyo Women's Medical University Adachi Medical Center, Tokyo, Japan
| | - Yuichi Kubota
- Department of Neurosurgery, Tokyo Women's Medical University Adachi Medical Center, Tokyo, Japan
| | - Mikhail F Chernov
- Department of Neurosurgery, Tokyo Women's Medical University Adachi Medical Center, Tokyo, Japan.
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Fiore G, Tariciotti L, Bertani GA, Gagliano D, D’Ammando A, Ampollini AM, Schisano L, Borsa S, Pluderi M, Locatelli M, Caroli M. Surgery vs. Radiosurgery for Patients with Localized Metastatic Brain Disease: A Systematic Review with Meta-Analysis of Randomized Controlled Trials. Cancers (Basel) 2023; 15:3802. [PMID: 37568618 PMCID: PMC10417431 DOI: 10.3390/cancers15153802] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2023] [Revised: 07/18/2023] [Accepted: 07/25/2023] [Indexed: 08/13/2023] Open
Abstract
Purpose: To analyze the efficacy and safety of surgery compared to radiosurgery (RS), combined or not with whole brain radiotherapy (WBRT), for localized metastatic brain disease. Methods: A systematic review with meta-analysis was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. The inclusion criteria were limited to randomized controlled trials (RCTs) that compared surgery and RS for patients with up to 3 metastases (median diameter ≤ 4 cm). The primary outcomes were represented by overall survival (OS) and local brain progression-free survival (PFS), with the rate of complications as a secondary outcome. The pooled estimates were calculated using random forest models. The risk of bias was evaluated using the RoB2 revised tool and the certainty of the evidence was assessed according to the GRADE guidelines. Results: In total, 11,256 records were identified through database and register searches. After study selection, 3 RCTs and 353 patients were included in the quantitative synthesis. Surgery and RS represented the main intervention arms in all the included RCTs. Conclusions: A low level of evidence suggests that RS alone and surgery followed by WBRT provide an equal rate of local brain PFS in patients with localized metastatic brain disease. There is a very low level of evidence that surgery and RS as main interventions offer equivalent OS in the population investigated. A reliable assessment of the complication rates among surgery and RS was not achievable. The lack of high-certainty evidence either for superiority or equivalence of these treatments emphasizes the need for further, more accurate, RCTs comparing surgery and RS as local treatment in patients with oligometastatic brain disease.
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Affiliation(s)
- Giorgio Fiore
- Unit of Neurosurgery, IRCCS Ca’ Granda Foundation Ospedale Maggiore Policlinico, Via Francesco Sforza, 35, 20122 Milan, Italy
- Department of Medical and Surgical Pathophysiology and Transplantation, University of Milan, 20122 Milan, Italy
- Department of Neurosurgery, National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, UK
| | - Leonardo Tariciotti
- Unit of Neurosurgery, IRCCS Ca’ Granda Foundation Ospedale Maggiore Policlinico, Via Francesco Sforza, 35, 20122 Milan, Italy
- Department of Medical and Surgical Pathophysiology and Transplantation, University of Milan, 20122 Milan, Italy
| | - Giulio Andrea Bertani
- Unit of Neurosurgery, IRCCS Ca’ Granda Foundation Ospedale Maggiore Policlinico, Via Francesco Sforza, 35, 20122 Milan, Italy
| | - Dario Gagliano
- Unit of Neurosurgery, IRCCS Ca’ Granda Foundation Ospedale Maggiore Policlinico, Via Francesco Sforza, 35, 20122 Milan, Italy
- Department of Medical and Surgical Pathophysiology and Transplantation, University of Milan, 20122 Milan, Italy
| | - Antonio D’Ammando
- Unit of Neurosurgery, IRCCS Ca’ Granda Foundation Ospedale Maggiore Policlinico, Via Francesco Sforza, 35, 20122 Milan, Italy
| | - Antonella Maria Ampollini
- Unit of Neurosurgery, IRCCS Ca’ Granda Foundation Ospedale Maggiore Policlinico, Via Francesco Sforza, 35, 20122 Milan, Italy
| | - Luigi Schisano
- Unit of Neurosurgery, IRCCS Ca’ Granda Foundation Ospedale Maggiore Policlinico, Via Francesco Sforza, 35, 20122 Milan, Italy
| | - Stefano Borsa
- Unit of Neurosurgery, IRCCS Ca’ Granda Foundation Ospedale Maggiore Policlinico, Via Francesco Sforza, 35, 20122 Milan, Italy
| | - Mauro Pluderi
- Unit of Neurosurgery, IRCCS Ca’ Granda Foundation Ospedale Maggiore Policlinico, Via Francesco Sforza, 35, 20122 Milan, Italy
| | - Marco Locatelli
- Unit of Neurosurgery, IRCCS Ca’ Granda Foundation Ospedale Maggiore Policlinico, Via Francesco Sforza, 35, 20122 Milan, Italy
- Department of Medical and Surgical Pathophysiology and Transplantation, University of Milan, 20122 Milan, Italy
| | - Manuela Caroli
- Unit of Neurosurgery, IRCCS Ca’ Granda Foundation Ospedale Maggiore Policlinico, Via Francesco Sforza, 35, 20122 Milan, Italy
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Rostampour N, Rezaeian S, Sarbakhsh P, Meola A, Choupani J, Doosti-Irani A, Nemati H, Almasi T, Badrigilan S, Chang SD. Efficacy of Stereotactic Radiosurgery as Single or Combined Therapy for Brain Metastasis: A Systematic Review and Meta-Analysis. Crit Rev Oncol Hematol 2023; 186:104015. [PMID: 37146702 DOI: 10.1016/j.critrevonc.2023.104015] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2020] [Revised: 03/22/2023] [Accepted: 05/01/2023] [Indexed: 05/07/2023] Open
Abstract
To determine the efficacy of stereotactic radiosurgery (SRS) in treating patients with brain metastases (BMs), a network meta-analysis (NMA) of randomized controlled trials (RCTs) and a direct comparison of cohort studies were performed. Relevant literature regarding the effectiveness of SRS alone and in combination with whole-brain radiotherapy (WBRT) and surgery was retrieved using systematic database searches up to April 2019. The patterns of overall survival (OS), one-year OS, progression-free survival (PFS), one-year local brain control (LBC), one-year distant brain control (DBC), neurological death (ND), and complication rate were analyzed. A total of 18 RCTs and 37 cohorts were included in the meta-analysis. Our data revealed that SRS carried a better OS than SRS+WBRT (p= 0.048) and WBRT (p= 0.041). Also, SRS+WBRT demonstrated a significantly improved PFS, LBC, and DBC compared to WBRT alone and SRS alone. Finally, SRS achieved the same LBC as high as surgery, but intracranial relapse occurred considerably more frequently in the absence of WBRT. However, there were not any significant differences in ND and toxicities between SRS and other groups. Therefore, SRS alone may be a better alternative since increased patient survival may outweigh the increased risk of brain tumor recurrence associated with it.
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Affiliation(s)
- Nima Rostampour
- Department of Medical Physics, School of Medcine, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Shahab Rezaeian
- Research Center for Environmental Determinants of Health (RCEDH), Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran; Epidemiology and Biostatistics Department, School of Public Health, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Parvin Sarbakhsh
- Research Center for Environmental Determinants of Health (RCEDH), Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Antonio Meola
- Depratment of Neurosurgery, Stanford University School of Medicine, Stanford, California, USA
| | - Jalal Choupani
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Amin Doosti-Irani
- Department of Epidemiology, School of Public Health, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Hossein Nemati
- Department of Epidemiology, School of Health, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Tinoosh Almasi
- Department of Medical Physics, School of Medcine, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Samireh Badrigilan
- Department of Medical Physics, School of Medcine, Kermanshah University of Medical Sciences, Kermanshah, Iran.
| | - Steven D Chang
- Depratment of Neurosurgery, Stanford University School of Medicine, Stanford, California, USA.
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Singh K, Saxena S, Khosla AA, McDermott MW, Kotecha RR, Ahluwalia MS. Update on the Management of Brain Metastasis. Neurotherapeutics 2022; 19:1772-1781. [PMID: 36422836 PMCID: PMC9723062 DOI: 10.1007/s13311-022-01312-w] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/03/2022] [Indexed: 11/27/2022] Open
Abstract
Brain metastases occur in almost one-third of adult patients with solid tumor malignancies and lead to considerable patient morbidity and mortality. The rising incidence of brain metastases has been ascribed to the development of better imaging and screening techniques and the formulation of better systemic therapies. Until recently, the multimodal management of brain metastases focused primarily on the utilization of neurosurgical techniques, with varying combinations of whole-brain radiation therapy and stereotactic radio-surgical procedures. Over the past 2 decades, in particular, the increment in knowledge pertaining to molecular genetics and the pathogenesis of brain metastases has led to significant developments in targeted therapies and immunotherapies. This review article highlights the recent updates in the management of brain metastases with an emphasis on novel systemic therapies.
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Affiliation(s)
- Karanvir Singh
- Division of Medical Oncology, Miami Cancer Institute, Baptist Health South Florida, Miami, FL, 33176, USA
| | - Shreya Saxena
- Division of Medical Oncology, Miami Cancer Institute, Baptist Health South Florida, Miami, FL, 33176, USA
| | - Atulya A Khosla
- Division of Medical Oncology, Miami Cancer Institute, Baptist Health South Florida, Miami, FL, 33176, USA
| | - Michael W McDermott
- Division of Neurosurgery, Miami Neuroscience Institute, Baptist Health South Florida, Miami, FL, 33176, USA
- Herbert Wertheim College of Medicine, Florida International University, Miami, FL, 33199, USA
| | - Rupesh R Kotecha
- Division of Radiation Oncology, Miami Cancer Institute, Baptist Health South Florida, Miami, FL, 33176, USA
- Herbert Wertheim College of Medicine, Florida International University, Miami, FL, 33199, USA
| | - Manmeet S Ahluwalia
- Division of Medical Oncology, Miami Cancer Institute, Baptist Health South Florida, Miami, FL, 33176, USA.
- Herbert Wertheim College of Medicine, Florida International University, Miami, FL, 33199, USA.
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Deng H, Xiong B, Gao Y, Wu Y, Wang W. Stereotactic radiosurgery combined with immune checkpoint inhibitors for brain metastasis: A systematic review and meta-analysis. Asian J Surg 2022; 46:1917-1923. [PMID: 36207214 DOI: 10.1016/j.asjsur.2022.09.080] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2022] [Revised: 09/05/2022] [Accepted: 09/19/2022] [Indexed: 11/02/2022] Open
Abstract
Many studies have reported the combination of radiosurgery and immune checkpoint inhibitors (ICI) in the treatment of brain metastasis, but these studies have not reached a consistent conclusion. Therefore, we conducted this systematic review and meta-analysis to evaluate the effect of combination therapy compared with radiosurgery alone on the prognosis of patients with brain metastasis. The Pubmed-MEDLINE and Ovid-EMBASE databases were comprehensively searched to identify relevant articles until May 5, 2022. The search results were filtered by the inclusion and exclusion criteria described in this paper. The pooled hazard ratios (HR) with 95% confidence intervals (CI) were presented as estimates effect to reflect the effect of combined therapy on each outcome. A total of 17 eligible studies covering 2079 patients were included in this meta-analysis. The pooled results showed that the use of targeted drugs could significantly improve the overall survival (HR = 0.62, 95%CI: 0.51-0.76; P<0.01), reduce the risk of local recurrence (HR = 0.48, 95%CI: 0.38-0.62; P<0.01) and distant brain recurrence (HR = 0.70, 95%CI: 0.50-0.97; P<0.05). Overall, SRS combined with ICIs could significantly improve overall survival, local control, and distant brain control of patients with brain metastasis compared to SRS alone, but the effect varies for different pathological types. Our results verified the rationality of the current treatment strategy for brain metastasis which emphasizes the combination of local and systematic therapy.
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11
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Voglis S, Schaller V, Müller T, Gönel M, Winklhofer S, Mangana J, Dummer R, Serra C, Weller M, Regli L, Le Rhun E, Neidert MC. Maximal surgical tumour load reduction in immune-checkpoint inhibitor naïve patients with melanoma brain metastases correlates with prolonged survival. Eur J Cancer 2022; 175:158-168. [PMID: 36126476 DOI: 10.1016/j.ejca.2022.08.020] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2022] [Revised: 08/04/2022] [Accepted: 08/16/2022] [Indexed: 11/27/2022]
Abstract
BACKGROUND Recent therapeutic advances in metastatic melanoma have led to improved overall survival (OS) rates, with consequently an increased incidence of brain metastases (BM). The role of BM resection in the era of targeted and immunotherapy should be reassessed. In the current study we analysed the role of residual intracranial tumour load in a cohort of melanoma BM patients. METHODS Retrospective single-centre analysis of a prospective registry of resected melanoma BM from 2013 to 2021. Correlations of residual tumour volume and outcome were determined with respect to patient, tumour and treatment regimens characteristics. RESULTS 121 individual patients (66% male, mean age 59.9 years) were identified and included in the study. Pre- and postoperative systemic treatments included BRAF/MEK inhibitors, as well as combination or monotherapy of immune-checkpoint inhibitors (ICIs). Median OS of the entire cohort was 20 months. Cox proportional-hazard analysis revealed postoperative anti-CTLA4+anti-PD-1 therapy (HR 0.07, p = .01) and postoperative residual intracranial tumour burden (HR 1.4, p = .027) as significant predictors for OS. Further analysis revealed that ICI-naïve patients with residual tumour volume ≤3.5 cm3 and postoperative ICI showed significantly prolonged OS compared to patients with residual volume >3.5 cm3 (p < .0001). Subgroup analysis of ICI-naïve patients showed steroid intake postoperatively to be negatively associated with OS, however residual tumour volume ≤3.5 cm3 remained independently correlated with superior OS (HR 0.14, p < .001). CONCLUSION Besides known predictive factors like postoperative ICI, a maximal intracranial tumour burden reduction seems to be beneficial, especially in ICI-naïve patients. This highlights the importance of local CNS control and the need to further investigating the role of initial surgical tumour load reduction in randomised clinical trials.
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Affiliation(s)
- Stefanos Voglis
- Department of Neurosurgery, Clinical Neuroscience Center, University Hospital and University of Zurich, Zurich, Switzerland.
| | - Valentina Schaller
- Department of Neurosurgery, Clinical Neuroscience Center, University Hospital and University of Zurich, Zurich, Switzerland
| | - Timothy Müller
- Department of Neurosurgery, Clinical Neuroscience Center, University Hospital and University of Zurich, Zurich, Switzerland
| | - Meltem Gönel
- Department of Neurosurgery, Clinical Neuroscience Center, University Hospital and University of Zurich, Zurich, Switzerland
| | - Sebastian Winklhofer
- Department of Neuroradiology, Clinical Neuroscience Center, University Hospital and University of Zurich, Zurich, Switzerland
| | - Joana Mangana
- Department of Dermatology, University Hospital and University of Zurich, Zurich, Switzerland
| | - Reinhard Dummer
- Department of Dermatology, University Hospital and University of Zurich, Zurich, Switzerland
| | - Carlo Serra
- Department of Neurosurgery, Clinical Neuroscience Center, University Hospital and University of Zurich, Zurich, Switzerland
| | - Michael Weller
- Department of Neurology, Clinical Neuroscience Center, University Hospital and University of Zurich, Zurich, Switzerland
| | - Luca Regli
- Department of Neurosurgery, Clinical Neuroscience Center, University Hospital and University of Zurich, Zurich, Switzerland
| | - Emilie Le Rhun
- Department of Neurosurgery, Clinical Neuroscience Center, University Hospital and University of Zurich, Zurich, Switzerland; Department of Neurology, Clinical Neuroscience Center, University Hospital and University of Zurich, Zurich, Switzerland
| | - Marian C Neidert
- Department of Neurosurgery, Clinical Neuroscience Center, University Hospital and University of Zurich, Zurich, Switzerland; Department of Neurosurgery, Cantonal Hospital St.Gallen, University of St.Gallen Medical School, St.Gallen, Switzerland
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12
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Krist DT, Naik A, Thompson CM, Kwok SS, Janbahan M, Olivero WC, Hassaneen W. Management of Brain Metastasis. Surgical Resection versus Stereotactic Radiotherapy: A Meta-analysis. Neurooncol Adv 2022; 4:vdac033. [PMID: 35386568 PMCID: PMC8982204 DOI: 10.1093/noajnl/vdac033] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Abstract
Abstract
Background
Treatment of metastatic brain tumors often involves radiotherapy with or without surgical resection as the first step. However, the indications for when to use surgery are not clearly defined for certain tumor sizes and multiplicity. This study seeks to determine whether resection of brain metastases versus exclusive radiotherapy provided improved survival and local control in cases where metastases are limited in number and diameter.
Methods
According to PRISMA guidelines, this meta-analysis compares outcomes from treatment of a median number of brain metastases ≤4 with a median diameter ≤4 cm with exclusive radiotherapy versus surgery followed by radiotherapy. Four randomized control trials and 11 observational studies (1693 patients) met inclusion criteria. For analysis, studies were grouped based on whether radiation involved stereotactic radiosurgery (SRS) or whole-brain radiotherapy (WBRT).
Results
In both analyses, there was no difference in survival between surgery ±SRS versus SRS alone two years after treatment (OR 1.89 (95% CI: 0.47 - 7.55, p = 0.23) or surgery + WBRT versus radiotherapy alone (either WBRT and/or SRS) (OR 1.18 (95% CI: 0.76 – 1.84, p = 0.46). However, surgical patients demonstrated greater risk for local tumor recurrence compared to SRS alone (OR 2.20 (95% CI: 1.49 - 3.25, p < 0.0001)) and compared to WBRT/SRS (OR 2.93; 95% CI: 1.68 - 5.13, p = 0.0002).
Conclusion
The higher incidence of local tumor recurrence for surgical patients suggests that more prospective studies are needed to clarify outcomes for treatment of 1-4 metastasis less than 4 cm diameter.
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Affiliation(s)
- David T Krist
- Department of Neurosurgery, Carle Foundation Hospital, Urbana, IL
- Carle Illinois College of Medicine, Champaign, IL
| | - Anant Naik
- Department of Neurosurgery, Carle Foundation Hospital, Urbana, IL
- Carle Illinois College of Medicine, Champaign, IL
| | - Charee M Thompson
- Carle Illinois College of Medicine, Champaign, IL
- Department of Communication, University of Illinois at Urbana-Champaign, Urbana, IL
| | - Susanna S Kwok
- Department of Neurosurgery, Carle Foundation Hospital, Urbana, IL
- Carle Illinois College of Medicine, Champaign, IL
| | - Mika Janbahan
- Department of Neurosurgery, Carle Foundation Hospital, Urbana, IL
- Carle Illinois College of Medicine, Champaign, IL
| | - William C Olivero
- Department of Neurosurgery, Carle Foundation Hospital, Urbana, IL
- Carle Illinois College of Medicine, Champaign, IL
| | - Wael Hassaneen
- Department of Neurosurgery, Carle Foundation Hospital, Urbana, IL
- Carle Illinois College of Medicine, Champaign, IL
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13
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Ramos A, Giantini-Larsen A, Pannullo SC, Brandmaier A, Knisely J, Magge R, Wilcox JA, Pavlick AC, Ma B, Pisapia D, Ashamalla H, Ramakrishna R. A multidisciplinary management algorithm for brain metastases. Neurooncol Adv 2022; 4:vdac176. [PMID: 36532509 PMCID: PMC9749403 DOI: 10.1093/noajnl/vdac176] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/10/2023] Open
Abstract
The incidence of brain metastases continues to present a management issue despite the advent of improved systemic control and overall survival. While the management of oligometastatic disease (ie, 1-4 brain metastases) with surgery and radiation has become fairly straightforward in the era of radiosurgery, the management of patients with multiple metastatic brain lesions can be challenging. Here we review the available evidence and provide a multidisciplinary management algorithm for brain metastases that incorporates the latest advances in surgery, radiation therapy, and systemic therapy while taking into account the latest in precision medicine-guided therapies. In particular, we argue that whole-brain radiation therapy can likely be omitted in most patients as up-front therapy.
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Affiliation(s)
- Alexander Ramos
- Department of Neurological Surgery, Weill Cornell Medicine, New York Presbyterian Hospital, New York, New York, USA
| | - Alexandra Giantini-Larsen
- Department of Neurological Surgery, Weill Cornell Medicine, New York Presbyterian Hospital, New York, New York, USA
| | - Susan C Pannullo
- Department of Neurological Surgery, Weill Cornell Medicine, New York Presbyterian Hospital, New York, New York, USA
| | - Andrew Brandmaier
- Department of Radiation Oncology, Weill Cornell Medicine, New York Presbyterian Hospital, New York, New York, USA
| | - Jonathan Knisely
- Department of Radiation Oncology, Weill Cornell Medicine, New York Presbyterian Hospital, New York, New York, USA
| | - Rajiv Magge
- Department of Neurology, Weill Cornell Medicine, New York Presbyterian Hospital, New York, New York, USA
| | - Jessica A Wilcox
- Department of Neurology, Weill Cornell Medicine, New York Presbyterian Hospital, New York, New York, USA
- Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - Anna C Pavlick
- Department of Oncology, Weill Cornell Medicine, New York Presbyterian, New York, New York, USA
| | - Barbara Ma
- Department of Oncology, Weill Cornell Medicine, New York Presbyterian, New York, New York, USA
| | - David Pisapia
- Department of Pathology, Weill Cornell Medicine, New York Presbyterian, New York, New York, USA
| | - Hani Ashamalla
- Department of Neurology, Weill Cornell Medicine, New York Presbyterian Hospital, New York, New York, USA
| | - Rohan Ramakrishna
- Department of Neurological Surgery, Weill Cornell Medicine, New York Presbyterian Hospital, New York, New York, USA
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14
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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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15
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Loo M, Clavier JB, Attal Khalifa J, Moyal E, Khalifa J. Dose-Response Effect and Dose-Toxicity in Stereotactic Radiotherapy for Brain Metastases: A Review. Cancers (Basel) 2021; 13:cancers13236086. [PMID: 34885193 PMCID: PMC8657210 DOI: 10.3390/cancers13236086] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2021] [Revised: 11/26/2021] [Accepted: 11/29/2021] [Indexed: 11/29/2022] Open
Abstract
Simple Summary Brain metastases are one of the most frequent complications for cancer patients. Stereotactic radiosurgery is considered a cornerstone treatment for patients with limited brain metastases and the ideal dose and fractionation schedule still remain unknown. The aim of this literature review is to discuss the dose-effect relation in brain metastases treated by stereotactic radiosurgery, accounting for fractionation and technical considerations. Abstract For more than two decades, stereotactic radiosurgery has been considered a cornerstone treatment for patients with limited brain metastases. Historically, radiosurgery in a single fraction has been the standard of care but recent technical advances have also enabled the delivery of hypofractionated stereotactic radiotherapy for dedicated situations. Only few studies have investigated the efficacy and toxicity profile of different hypofractionated schedules but, to date, the ideal dose and fractionation schedule still remains unknown. Moreover, the linear-quadratic model is being debated regarding high dose per fraction. Recent studies shown the radiation schedule is a critical factor in the immunomodulatory responses. The aim of this literature review was to discuss the dose–effect relation in brain metastases treated by stereotactic radiosurgery accounting for fractionation and technical considerations. Efficacy and toxicity data were analyzed in the light of recent published data. Only retrospective and heterogeneous data were available. We attempted to present the relevant data with caution. A BED10 of 40 to 50 Gy seems associated with a 12-month local control rate >70%. A BED10 of 50 to 60 Gy seems to achieve a 12-month local control rate at least of 80% at 12 months. In the brain metastases radiosurgery series, for single-fraction schedule, a V12 Gy < 5 to 10 cc was associated to 7.1–22.5% radionecrosis rate. For three-fractions schedule, V18 Gy < 26–30 cc, V21 Gy < 21 cc and V23 Gy < 5–7 cc were associated with about 0–14% radionecrosis rate. For five-fractions schedule, V30 Gy < 10–30 cc, V 28.8 Gy < 3–7 cc and V25 Gy < 16 cc were associated with about 2–14% symptomatic radionecrosis rate. There are still no prospective trials comparing radiosurgery to fractionated stereotactic irradiation.
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Affiliation(s)
- Maxime Loo
- Radiotherapy Department, University Cancer Institute of Toulouse—Oncopôle, 31100 Toulouse, France; (J.A.K.); (E.M.); (J.K.)
- Correspondence:
| | - Jean-Baptiste Clavier
- Radiotherapy Department, Strasbourg Europe Cancer Institute (ICANS), 67033 Strasbourg, France;
| | - Justine Attal Khalifa
- Radiotherapy Department, University Cancer Institute of Toulouse—Oncopôle, 31100 Toulouse, France; (J.A.K.); (E.M.); (J.K.)
| | - Elisabeth Moyal
- Radiotherapy Department, University Cancer Institute of Toulouse—Oncopôle, 31100 Toulouse, France; (J.A.K.); (E.M.); (J.K.)
| | - Jonathan Khalifa
- Radiotherapy Department, University Cancer Institute of Toulouse—Oncopôle, 31100 Toulouse, France; (J.A.K.); (E.M.); (J.K.)
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16
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Intracranial malignant melanoma: An egyptian institute experience. INTERDISCIPLINARY NEUROSURGERY 2021. [DOI: 10.1016/j.inat.2021.101370] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
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17
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Mantovani C, Gastino A, Cerrato M, Badellino S, Ricardi U, Levis M. Modern Radiation Therapy for the Management of Brain Metastases From Non-Small Cell Lung Cancer: Current Approaches and Future Directions. Front Oncol 2021; 11:772789. [PMID: 34796118 PMCID: PMC8593461 DOI: 10.3389/fonc.2021.772789] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2021] [Accepted: 10/18/2021] [Indexed: 12/19/2022] Open
Abstract
Brain metastases (BMs) represent the most frequent event during the course of Non-Small Cell Lung Cancer (NSCLC) disease. Recent advancements in the diagnostic and therapeutic procedures result in increased incidence and earlier diagnosis of BMs, with an emerging need to optimize the prognosis of these patients through the adoption of tailored treatment solutions. Nowadays a personalized and multidisciplinary approach should rely on several clinical and molecular factors like patient’s performance status, extent and location of brain involvement, extracranial disease control and the presence of any “druggable” molecular target. Radiation therapy (RT), in all its focal (radiosurgery and fractionated stereotactic radiotherapy) or extended (whole brain radiotherapy) declinations, is a cornerstone of BMs management, either alone or combined with surgery and systemic therapies. Our review aims to provide an overview of the many modern RT solutions available for the treatment of BMs from NSCLC in the different clinical scenarios (single lesion, oligo and poly-metastasis, leptomeningeal carcinomatosis). This includes a detailed review of the current standard of care in each setting, with a presentation of the literature data and of the possible technical solutions to offer a “state-of-art” treatment to these patients. In addition to the validated treatment options, we will also discuss the future perspectives on emerging RT technical strategies (e.g., hippocampal avoidance whole brain RT, simultaneous integrated boost, radiosurgery for multiple lesions), and present the innovative and promising findings regarding the combination of novel targeted agents such as tyrosine kinase inhibitors and immune checkpoint inhibitors with brain irradiation.
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Affiliation(s)
| | | | - Marzia Cerrato
- Department of Oncology, University of Torino, Torino, Italy
| | | | | | - Mario Levis
- Department of Oncology, University of Torino, Torino, Italy
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18
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Lamba N, Catalano PJ, Whitehouse C, Martin KL, Mendu ML, Haas-Kogan DA, Wen PY, Aizer AA. Emergency department visits and inpatient hospitalizations among older patients with brain metastases: a dual population- and institution-level analysis. Neurooncol Pract 2021; 8:569-580. [PMID: 34691748 DOI: 10.1093/nop/npab029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Background Older patients with brain metastases (BrM) commonly experience symptoms that prompt acute medical evaluation. We characterized emergency department (ED) visits and inpatient hospitalizations in this population. Methods We identified 17 789 and 361 Medicare enrollees diagnosed with BrM using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database (2010-2016) and an institutional database (2007-2016), respectively. Predictors of ED visits and hospitalizations were assessed using Poisson regression. Results The institutional cohort averaged 3.3 ED visits/1.9 hospitalizations per person-year, with intracranial disease being the most common reason for presentation/admission. SEER-Medicare patients averaged 2.8 ED visits/2.0 hospitalizations per person-year. For patients with synchronous BrM (N = 7834), adjusted risk factors for ED utilization and hospitalization, respectively, included: male sex (rate ratio [RR] = 1.15 [95% CI = 1.09-1.22], P < .001; RR = 1.21 [95% CI = 1.13-1.29], P < .001); African American vs white race (RR = 1.30 [95% CI = 1.18-1.42], P < .001; RR = 1.25 [95% CI = 1.13-1.39], P < .001); unmarried status (RR = 1.07 [95% CI = 1.01-1.14], P = .02; RR = 1.09 [95% CI = 1.02-1.17], P = .01); Charlson comorbidity score >2 (RR = 1.27 [95% CI = 1.17-1.37], P < .001; RR = 1.36 [95% CI = 1.24-1.49], P < .001); and receipt of non-stereotactic vs stereotactic radiation (RR = 1.44 [95% CI = 1.34-1.55, P < .001; RR = 1.49 [95% CI = 1.37-1.62, P < .001). For patients with metachronous BrM (N = 9955), ED visits and hospitalizations were more common after vs before BrM diagnosis (2.6 vs 1.2 ED visits per person-year; 1.8 vs 0.9 hospitalizations per person-year, respectively; RR = 2.24 [95% CI = 2.15-2.33], P < .001; RR = 2.06 [95% CI = 1.98-2.15], P < .001, respectively). Conclusions Older patients with BrM commonly receive hospital-level care secondary to intracranial disease, especially in select subpopulations. Enhanced care coordination, closer outpatient follow-up, and patient navigator programs seem warranted for this population.
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Affiliation(s)
- Nayan Lamba
- Harvard Radiation Oncology Program, Harvard University, Boston, Massachusetts, USA.,Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Boston, Massachusetts, USA
| | - Paul J Catalano
- Department of Biostatistics, Harvard T.H. Chan School of Public Health, and Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
| | - Colleen Whitehouse
- Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Boston, Massachusetts, USA
| | - Kate L Martin
- Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Boston, Massachusetts, USA
| | - Mallika L Mendu
- Partners Healthcare Center for Population Health Management and Department of Quality and Safety, Brigham and Women's Hospital, Boston, Massachusetts, USA
| | - Daphne A Haas-Kogan
- Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Boston, Massachusetts, USA
| | - Patrick Y Wen
- Center for Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Ayal A Aizer
- Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Boston, Massachusetts, USA
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19
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Wang B, Guo H, Xu H, Yu H, Chen Y, Zhao G. Research Progress and Challenges in the Treatment of Central Nervous System Metastasis of Non-Small Cell Lung Cancer. Cells 2021; 10:2620. [PMID: 34685600 PMCID: PMC8533870 DOI: 10.3390/cells10102620] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2021] [Revised: 09/06/2021] [Accepted: 09/25/2021] [Indexed: 12/26/2022] Open
Abstract
Non-small cell lung cancer (NSCLC) is one of the most common malignant tumors and has high morbidity and mortality rates. Central nervous system (CNS) metastasis is one of the most frequent complications in patients with NSCLC and seriously affects the quality of life (QOL) and overall survival (OS) of patients, with a median OS of untreated patients of only 1-3 months. There are various treatment methods for NSCLC CNS metastasis, including surgery, chemotherapy, radiotherapy, targeted therapy, and immunotherapy, which do not meet the requirements of patients in terms of improving OS and QOL. There are still many problems in the treatment of NSCLC CNS metastasis that need to be solved urgently. This review summarizes the research progress in the treatment of NSCLC CNS metastasis to provide a reference for clinical practice.
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Affiliation(s)
- Bin Wang
- Department of Neurosurgery, The First Hospital of Jilin University, Changchun 130021, China; (B.W.); (H.X.); (H.Y.)
| | - Hanfei Guo
- Cancer Center, The First Hospital of Jilin University, Changchun 130021, China;
| | - Haiyang Xu
- Department of Neurosurgery, The First Hospital of Jilin University, Changchun 130021, China; (B.W.); (H.X.); (H.Y.)
| | - Hongquan Yu
- Department of Neurosurgery, The First Hospital of Jilin University, Changchun 130021, China; (B.W.); (H.X.); (H.Y.)
| | - Yong Chen
- Department of Neurosurgery, The First Hospital of Jilin University, Changchun 130021, China; (B.W.); (H.X.); (H.Y.)
| | - Gang Zhao
- Department of Neurosurgery, The First Hospital of Jilin University, Changchun 130021, China; (B.W.); (H.X.); (H.Y.)
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20
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Lai YL, Kang JH, Hsu CY, Lee JI, Cheng WF, Chen YL, Lee YY. Gamma Knife Radiosurgery-Based Combination Treatment Strategies Improve Survival in Patients With Central Nervous System Metastases From Epithelial Ovarian Cancer: A Retrospective Analysis of Two Academic Institutions in Korea and Taiwan. Front Oncol 2021; 11:719936. [PMID: 34513698 PMCID: PMC8429898 DOI: 10.3389/fonc.2021.719936] [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: 06/03/2021] [Accepted: 08/12/2021] [Indexed: 11/13/2022] Open
Abstract
Central nervous system (CNS) metastases from epithelial ovarian cancer (EOC) are rare. We investigated the clinico-pathological prognostic factors of patients with CNS metastases from EOC and compared the outcomes of various treatment modalities. We retrospectively reviewed the records of patients with CNS metastases from EOC between 2000 and 2020. Information on the clinical and pathological characteristics, treatment, and outcomes of these patients was retrieved from Samsung Medical Center and National Taiwan University Hospital. A total of 94 patients with CNS metastases were identified among 6,300 cases of EOC, resulting in an incidence of 1.49%. Serous histological type [hazard ratio (HR): 0.49 (95% confidence interval [CI] 0.25-0.95), p=0.03], progressive disease [HR: 2.29 (95% CI 1.16-4.54), p=0.01], CNS involvement in first disease relapse [HR: 0.36 (95% CI 0.18-0.70), p=0.002], and gamma knife radiosurgery (GKS)-based combination treatment for EOC patients with CNS lesions [HR: 0.59 (95% CI 0.44-0.79), p<0.001] significantly impacted survival after diagnosis of CNS metastases. In a subgroup analysis, superior survival was observed in patients with CNS involvement not in first tumor recurrence who underwent GKS-based combination therapeutic regimens. The survival benefit of GKS-based treatment was not significant in patients with CNS involvement in first disease relapse, but a trend for longer survival was still observed. In conclusion, GKS-based combination treatment can be considered for the treatment of EOC patients with CNS metastases. The patients with CNS involvement not in first disease relapse could significantly benefit from GKS-based combination strategies.
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Affiliation(s)
- Yen-Ling Lai
- Department of Obstetrics and Gynecology, Hsin-Chu Branch, National Taiwan University Hospital, Hsin-Chu, Taiwan.,Department of Obstetrics and Gynecology, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Jun-Hyeok Kang
- Department of Obstetrics and Gynecology, Uijeongbu Eulji Medical Center, Eulji University School of Medicine, Uijeongbu-si, South Korea
| | - Che-Yu Hsu
- Division of Radiation oncology, Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan
| | - Jung-Il Lee
- Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Wen-Fang Cheng
- Department of Obstetrics and Gynecology, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Yu-Li Chen
- Department of Obstetrics and Gynecology, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Yoo-Young Lee
- Division of Gynecologic oncology, Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
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21
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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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22
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González L, Castro S, Villa E, Zomosa G. Surgical resection versus stereotactic radiosurgery on local recurrence and survival for patients with a single brain metastasis: a systematic review and meta-analysis. Br J Neurosurg 2021; 35:703-713. [PMID: 34431733 DOI: 10.1080/02688697.2021.1950623] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
BACKGROUND Brain metastases (BM) are the most frequent intracranial tumours in adults. In patients with solitary BM, surgical resection (SR) or stereotactic radiosurgery (SRS) is performed. There is limited evidence comparing one treatment over the other. OBJECTIVE To compare SR versus SRS on patients with solitary BMs, regarding local recurrence (LR) and overall survival (OS) conducting a systematic review and meta-analysis. METHODS Systematic review of literature following PRISMA guidelines, using the databases of Medline, Clinicaltrials.gov, Embase, Web of Science, Sciencedirect, CINAHL, Wiley Online Library, Springerlink and LILACS. Following study selection based on inclusion and exclusion criteria, data extraction and a critical analysis of the literature was performed according to the GRADE scale. For quantitative analysis, a random effects model was used. Data were synthetized and evaluated on a forest plot and funnel plot. RESULTS Two randomized clinical trials, four cohort studies and one case-control studies met our inclusion criteria for the qualitative analysis. None was excluded subsequently. Overall, 614 patients with single metastasis were included. Studies had high heterogeneity. Multiple significant variables affecting the outcome were signalized. Meta-analysis showed no significant differences for survival (HR, 1.10; 95% CI, 0.75-1.45) or LR (HR, 0.81; 95% CI, 0.42-1.20). CONCLUSIONS According to current evidence, in patients with a single small metastasis there is no statistically significant difference in OS or LR among the chosen techniques (SR or SRS). Multiple significant co-variables may affect both outcomes. Different outcomes better than OS should be evaluated in further randomized studies.
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Affiliation(s)
- Lucas González
- Faculty of Medicine, University of Chile, Santiago, Chile
| | | | - Eduardo Villa
- Faculty of Medicine, University of Chile, Santiago, Chile
| | - Gustavo Zomosa
- Department of Neurology & Neurosurgery, Hospital Clinico Universidad de Chile, Santiago, Chile
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23
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Fuchs J, Früh M, Papachristofilou A, Bubendorf L, Häuptle P, Jost L, Zippelius A, Rothschild SI. Resection of isolated brain metastases in non-small cell lung cancer (NSCLC) patients - evaluation of outcome and prognostic factors: A retrospective multicenter study. PLoS One 2021; 16:e0253601. [PMID: 34181677 PMCID: PMC8238224 DOI: 10.1371/journal.pone.0253601] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2020] [Accepted: 06/08/2021] [Indexed: 11/18/2022] Open
Abstract
BACKGROUND AND OBJECTIVES Brain metastases occur in about 30% of all patients with non-small cell lung cancer (NSCLC). In selected patients, long-term survival can be achieved by resection of brain metastases. In this retrospective study, we investigate the prognosis of NSCLC patients with resected brain metastases and possible prognostic factors. METHODS In 119 patients with NSCLC and resected brain metastases, we report the following parameters: extent of resection, resection status, postoperative complications and overall survival (OS). We used the log-rank test to compare unadjusted survival probabilities and multivariable Cox regression to investigate potential prognostic factors with respect to OS. RESULTS A total of 146 brain metastases were resected in 119 patients. The median survival was 18.0 months. Postoperative cerebral radiotherapy was performed in 86% of patients. Patients with postoperative radiotherapy had significantly longer survival (median OS 20.2 vs. 9.0 months, p = 0.002). The presence of multiple brain metastases was a negative prognostic factor (median OS 13.5 vs. 19.5 months, p = 0.006). Survival of patients with extracerebral metastases of NSCLC was significantly shorter than in patients who had exclusively brain metastases (median OS 14.0 vs. 23.1 months, p = 0.005). Both of the latter factors were independent prognostic factors for worse outcome in multivariate analysis. CONCLUSIONS Based on these data, resection of solitary brain metastases in patients with NSCLC and controlled extracerebral tumor disease is safe and leads to an overall favorable outcome. Postoperative radiotherapy is recommended to improve prognosis.
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Affiliation(s)
- Julia Fuchs
- Medical Oncology, Department Internal Medicine, University Hospital Basel, Basel, Switzerland
| | - Martin Früh
- Department of Medical Oncology and Hematology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland
- Department of Medical Oncology, University Hospital Bern, Bern, Switzerland
| | - Alexandros Papachristofilou
- Lung Cancer Center Basel, Comprehensive Cancer Center, University Hospital Basel, Basel, Switzerland
- Department of Radiation Oncology, University Hospital Basel, Basel, Switzerland
| | - Lukas Bubendorf
- Institute of Pathology, University Hospital Basel, Basel, Switzerland
| | - Pirmin Häuptle
- Department Oncology, Hematology and Transfusion Medicine, Cantonal Hospital Baselland, Liestal, Switzerland
| | - Lorenz Jost
- Medical Oncology, Cantonal Hospital Baselland, Bruderholz, Basel, Switzerland
| | - Alfred Zippelius
- Medical Oncology, Department Internal Medicine, University Hospital Basel, Basel, Switzerland
| | - Sacha I. Rothschild
- Medical Oncology, Department Internal Medicine, University Hospital Basel, Basel, Switzerland
- Lung Cancer Center Basel, Comprehensive Cancer Center, University Hospital Basel, Basel, Switzerland
- * E-mail:
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24
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Shah PP, Franke JL, Medikonda R, Jackson CM, Srivastava S, Choi J, Forde PM, Brahmer JR, Ettinger DS, Feliciano JL, Levy BP, Marrone KA, Naidoo J, Redmond KJ, Kleinberg LR, Lim M. Mutation status and postresection survival of patients with non-small cell lung cancer brain metastasis: implications of biomarker-driven therapy. J Neurosurg 2021; 136:56-66. [PMID: 34087798 DOI: 10.3171/2020.10.jns201787] [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: 05/19/2020] [Accepted: 10/02/2020] [Indexed: 11/06/2022]
Abstract
OBJECTIVE Non-small cell lung cancer (NSCLC) is the most common primary tumor to develop brain metastasis. Prognostic markers are needed to better determine survival after neurosurgical resection of intracranial disease. Given the importance of mutation subtyping in determining systemic therapy and overall prognosis of NSCLC, the authors examined the prognostic value of mutation status for postresection survival of patients with NSCLC brain metastasis. METHODS The authors retrospectively analyzed all cases of NSCLC brain metastasis with available molecular testing data that were resected by a single surgeon at a single academic center from January 2009 to February 2019. Mutation status, demographic characteristics, clinical factors, and treatments were analyzed. Association between predictive variables and overall survival after neurosurgery was determined with Cox regression. RESULTS Of the included patients (n = 84), 40% were male, 76% were smokers, the mean ± SD Karnofsky Performance Status was 85 ± 14, and the mean ± SD age at surgery was 63 ± 11 years. In total, 23%, 26%, and 4% of patients had EGFR, KRAS, and ALK/ROS1 alterations, respectively. On multivariate analysis, survival of patients with EGFR (HR 0.495, p = 0.0672) and KRAS (HR 1.380, p = 0.3617) mutations were not significantly different from survival of patients with wild-type (WT) tumor. However, the subgroup of patients with EGFR mutation who also received tyrosine kinase inhibitor (TKI) therapy had significantly prolonged survival (HR 0.421, p = 0.0471). In addition, postoperative stereotactic radiosurgery (HR 0.409, p = 0.0177) and resected tumor diameter < 3 cm (HR 0.431, p = 0.0146) were also significantly associated with prolonged survival, but Graded Prognostic Assessment score ≤ 1.0 (HR 2.269, p = 0.0364) was significantly associated with shortened survival. CONCLUSIONS Patients with EGFR mutation who receive TKI therapy may have better survival after resection of brain metastasis than patients with WT tumor. These results may inform counseling and decision-making regarding the appropriateness of resection of NSCLC brain metastasis.
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Affiliation(s)
| | | | | | | | | | | | - Patrick M Forde
- 2Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland
| | - Julie R Brahmer
- 2Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland
| | - David S Ettinger
- 2Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland
| | - Josephine L Feliciano
- 2Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland
| | - Benjamin P Levy
- 2Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland
| | - Kristen A Marrone
- 2Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland
| | - Jarushka Naidoo
- 2Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland
| | - Kristin J Redmond
- 3Radiation Oncology, Johns Hopkins University School of Medicine; and
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25
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Galanti D, Inno A, La Vecchia M, Borsellino N, Incorvaia L, Russo A, Gori S. Current treatment options for HER2-positive breast cancer patients with brain metastases. Crit Rev Oncol Hematol 2021; 161:103329. [PMID: 33862249 DOI: 10.1016/j.critrevonc.2021.103329] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2020] [Revised: 03/03/2021] [Accepted: 03/26/2021] [Indexed: 11/29/2022] Open
Abstract
Brain metastases (BMs) are frequently associated with HER2+ breast cancer (BC). Their management is based on a multi-modal strategy including both local treatment and systemic therapy. Despite therapeutic advance, BMs still have an adverse impact on survival and quality of life and the development of effective systemic therapy to prevent and treat BMs from HER2 + BC represents an unmet clinical need. Trastuzumab-based therapy has long been the mainstay of systemic therapy and over the last two decades other HER2-targeted agents including lapatinib, pertuzumab and trastuzumab emtansine, have been introduced in the clinical practice. More recently, novel agents such as neratinib, tucatinib and trastuzumab deruxtecan have been developed, with interesting activity against BMs. Further research is needed to better elucidate the best sequence of these agents and their combination with local treatment.
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Affiliation(s)
- Daniele Galanti
- Medical Oncology Unit, Buccheri La Ferla Fatebenefratelli Hospital, Palermo, Italy
| | - Alessandro Inno
- Medical Oncology Unit, IRCCS Sacro Cuore don Calabria Hospital, Negrar di Valpolicella, Verona, Italy
| | | | - Nicolò Borsellino
- Medical Oncology Unit, Buccheri La Ferla Fatebenefratelli Hospital, Palermo, Italy
| | - Lorena Incorvaia
- Department of Biomedicine, Neuroscience and Advanced Diagnostics (Bi.N.D.), Section of Medical Oncology, University of Palermo, 90127, Palermo, Italy
| | - Antonio Russo
- Department of Surgical, Oncological & Oral Sciences, Section of Medical Oncology, University of Palermo, 90127, Palermo, Italy.
| | - Stefania Gori
- Medical Oncology Unit, Buccheri La Ferla Fatebenefratelli Hospital, Palermo, Italy
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26
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Proescholdt MA, Schödel P, Doenitz C, Pukrop T, Höhne J, Schmidt NO, Schebesch KM. The Management of Brain Metastases-Systematic Review of Neurosurgical Aspects. Cancers (Basel) 2021; 13:1616. [PMID: 33807384 PMCID: PMC8036330 DOI: 10.3390/cancers13071616] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2021] [Revised: 03/23/2021] [Accepted: 03/26/2021] [Indexed: 02/07/2023] Open
Abstract
The multidisciplinary management of patients with brain metastases (BM) consists of surgical resection, different radiation treatment modalities, cytotoxic chemotherapy, and targeted molecular treatment. This review presents the current state of neurosurgical technology applied to achieve maximal resection with minimal morbidity as a treatment paradigm in patients with BM. In addition, we discuss the contribution of neurosurgical resection on functional outcome, advanced systemic treatment strategies, and enhanced understanding of the tumor biology.
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Affiliation(s)
- Martin A. Proescholdt
- Department of Neurosurgery, University Hospital Regensburg, 93053 Regensburg, Germany; (M.A.P.); (P.S.); (C.D.); (J.H.); (N.O.S.)
- Wilhelm Sander Neuro-Oncology Unit, University Hospital Regensburg, 93053 Regensbur, Germany;
| | - Petra Schödel
- Department of Neurosurgery, University Hospital Regensburg, 93053 Regensburg, Germany; (M.A.P.); (P.S.); (C.D.); (J.H.); (N.O.S.)
- Wilhelm Sander Neuro-Oncology Unit, University Hospital Regensburg, 93053 Regensbur, Germany;
| | - Christian Doenitz
- Department of Neurosurgery, University Hospital Regensburg, 93053 Regensburg, Germany; (M.A.P.); (P.S.); (C.D.); (J.H.); (N.O.S.)
- Wilhelm Sander Neuro-Oncology Unit, University Hospital Regensburg, 93053 Regensbur, Germany;
| | - Tobias Pukrop
- Wilhelm Sander Neuro-Oncology Unit, University Hospital Regensburg, 93053 Regensbur, Germany;
- Department of Medical Oncology, University Hospital Regensburg, 93053 Regensburg, Germany
| | - Julius Höhne
- Department of Neurosurgery, University Hospital Regensburg, 93053 Regensburg, Germany; (M.A.P.); (P.S.); (C.D.); (J.H.); (N.O.S.)
- Wilhelm Sander Neuro-Oncology Unit, University Hospital Regensburg, 93053 Regensbur, Germany;
| | - Nils Ole Schmidt
- Department of Neurosurgery, University Hospital Regensburg, 93053 Regensburg, Germany; (M.A.P.); (P.S.); (C.D.); (J.H.); (N.O.S.)
- Wilhelm Sander Neuro-Oncology Unit, University Hospital Regensburg, 93053 Regensbur, Germany;
| | - Karl-Michael Schebesch
- Department of Neurosurgery, University Hospital Regensburg, 93053 Regensburg, Germany; (M.A.P.); (P.S.); (C.D.); (J.H.); (N.O.S.)
- Wilhelm Sander Neuro-Oncology Unit, University Hospital Regensburg, 93053 Regensbur, Germany;
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27
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Gao C, Wang F, Suki D, Strom E, Li J, Sawaya R, Hsu L, Raghavendra A, Tripathy D, Ibrahim NK. Effects of systemic therapy and local therapy on outcomes of 873 breast cancer patients with metastatic breast cancer to brain: MD Anderson Cancer Center experience. Int J Cancer 2021; 148:961-970. [PMID: 32748402 DOI: 10.1002/ijc.33243] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2020] [Revised: 07/16/2020] [Accepted: 07/20/2020] [Indexed: 12/14/2022]
Abstract
Outcomes of treatments for patients with breast cancer brain metastasis (BCBM) remain suboptimal, especially for systemic therapy. To evaluate the effectiveness of systemic and local therapy (surgery [S], stereotactic radiosurgery [SRS] and whole brain radiotherapy [WBRT]) in BCBM patients, we analyzed the data of 873 BCBM patients from 1999 to 2012. The median overall survival (OS) and time to progression in the brain (TTP-b) after diagnosis of brain metastases (BM) were 9.1 and 7.1 months, respectively. WBRT prolonged OS in patients with multiple BM (hazard ratio [HR], 0.68; 95% CI, 0.52-0.88; P = .004). SRS alone, and surgery or SRS followed by WBRT (S/SRS + WBRT), were equivalent in OS and TTP-b (median OS, 14.9 vs 17.2 months; median TTP-b, 8.2 vs 8.6 months). Continued chemotherapy prolonged OS (HR, 0.35; 95% CI, 0.30-0.41; P < .001) and TTP-b (HR, 0.48; 95% CI, 0.33-0.70; P < .001), however, with no advantage of capecitabine over other chemotherapy agents used (median OS, 11.8 vs 12.4 months; median TTP-b, 7.2 vs 7.4 months). Patients receiving trastuzumab at diagnosis of BM, continuation of anti-HER2 therapy increased OS (HR, 0.53; 95% CI, 0.34-0.83; P = .005) and TTP-b (HR, 0.41; 95% CI, 0.23-0.74; P = .003); no additional benefit was seen with switching over between trastuzumab and lapatinib (median OS, 18.4 vs 22.7 months; median TTP-b: 7.4 vs 8.7 months). In conclusion, SRS or S/SRS + WBRT were equivalent for patients' OS and local control. Continuation systemic chemotherapy including anti-HER2 therapy improved OS and TTP-b with no demonstrable advantage of capecitabine and lapatinib over other agents of physicians' choice was observed.
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Affiliation(s)
- Chao Gao
- Department of Breast Medical Oncology, University of Texas, MD Anderson Cancer Center, Houston, Texas, USA
- Department of Radiation Oncology, The Fourth Hospital of Hebei Medical University, Hebei Medical University, Shijiazhuang, China
| | - Fuchenchu Wang
- Department of Biostatistics, University of Texas, MD Anderson Cancer Center, Houston, Texas, USA
| | - Dima Suki
- Department of Neurosurgery, University of Texas, MD Anderson Cancer Center, Houston, Texas, USA
| | - Eric Strom
- Department of Radiation Oncology, University of Texas, MD Anderson Cancer Center, Houston, Texas, USA
| | - Jing Li
- Department of Radiation Oncology, University of Texas, MD Anderson Cancer Center, Houston, Texas, USA
| | - Raymond Sawaya
- Department of Neurosurgery, University of Texas, MD Anderson Cancer Center, Houston, Texas, USA
| | - Limin Hsu
- Department of Breast Medical Oncology, University of Texas, MD Anderson Cancer Center, Houston, Texas, USA
| | - Akshara Raghavendra
- Department of Breast Medical Oncology, University of Texas, MD Anderson Cancer Center, Houston, Texas, USA
| | - Debu Tripathy
- Department of Breast Medical Oncology, University of Texas, MD Anderson Cancer Center, Houston, Texas, USA
| | - Nuhad K Ibrahim
- Department of Breast Medical Oncology, University of Texas, MD Anderson Cancer Center, Houston, Texas, USA
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Holub K, Louvel G. Poor performance status and brain metastases treatment: who may benefit from the stereotactic radiotherapy? J Neurooncol 2021; 152:383-393. [PMID: 33590401 DOI: 10.1007/s11060-021-03712-y] [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] [Received: 12/23/2020] [Accepted: 01/29/2021] [Indexed: 10/22/2022]
Abstract
BACKGROUND Poor Performance Status (PS) of cancer patients, defined as PS score 2-3, is an impediment for many drug- and irradiation-based treatments, supported by the trials that exclude subjects with PS < 1. Reports on the benefits of stereotactic radiotherapy (SRT) for brain metastases (BMs) in poor PS patients are scarce. We sought to review the characteristics and survival outcomes of this cohort, to assess who may benefit most from SRT. METHODS We retrospectively evaluated 73 patients with PS 2 or 3 (63 and 10 cases) treated with SRT for 150 BMs from 2012 to 2018. Patients' characteristics and post-SRT survival, stratified by concomitant systemic treatment (CST) were assessed using the Kaplan-Meier method (p-value < 0.05). RESULTS Non-small cell lung cancer was the most frequent primary tumor. Extracranial metastases were present in 86.3% of patients. The median overall survival (mOS) after SRT was estimated as 6.0 months (range 0.2-37.7), with 6- and 12-month survival rates of 51.0% and 21.0%, respectively. CST was administrated to 59.7% of patients (immunotherapy, target therapy or chemotherapy). Patients treated with CST presented larger mOS (6.7 vs. 4.4 months for patients treated with SRT alone, p = 0.3), and better 6- and 12-month survival rates (59% and 24% vs. 37% and 18% in patients not treated with CST). CONCLUSIONS Survival rate after SRT for BMs in poor performance patients, especially with PS 2, can justify SRT, in particular if an effective systemic treatment is available. Both SRT and CST should be more accessible for these patients in clinical practice.
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Affiliation(s)
- Katarzyna Holub
- Radiotherapy Department, Gustave Roussy Cancer Campus, Villejuif, France. .,Universitat de Barcelona, Barcelona, Spain.
| | - Guillaume Louvel
- Radiotherapy Department, Gustave Roussy Cancer Campus, Villejuif, France
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29
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Sadik ZHA, Hanssens PEJ, Verheul JB, Ardon H, Lie ST, van der Pol B, Beute GN, Fleischeuer REM, Leenstra S. Stereotactic cyst aspiration directly followed by Gamma Knife radiosurgery for large cystic brain metastases. Acta Neurochir (Wien) 2021; 163:343-350. [PMID: 32291592 DOI: 10.1007/s00701-020-04273-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2019] [Accepted: 02/19/2020] [Indexed: 10/24/2022]
Abstract
BACKGROUND Gamma Knife radiosurgery (GKRS) has been proven to be a successful primary treatment for metastatic brain tumors (BM). BM can come in cystic lesions and are often too large for GKRS. An alternative approach to treat cystic BM is stereotactic cyst aspiration (SCA) for volume reduction, making it suitable for GKRS afterwards. OBJECTIVE Our objective is evaluation of volumetric reduction after SCA, tumor control, and complications after SCA directly followed by GKRS. METHODS We performed a retrospective analysis of all patients who underwent SCA directly followed by GKRS at the Gamma Knife Center of the Elisabeth-Tweesteden Hospital in Tilburg between 2002 and 2015. In total, 54 patients had undergone this combined approach. Two patients were excluded because of prior intracranial treatment. The other 52 patients were included for analysis. RESULTS SCA resulted in a mean volumetric reduction of 56.5% (range 5.50-87.00%). In 83.6% of the tumors (46 tumors), SCA led to sufficient volumetric reduction making GKRS possible. The overall local tumor control (OLTC) of the aspirated lesions post-GKRS was 60.9% (28 out of 46 tumors). Median progression-free survival (PFS) and overall survival (OS) for all patients were 3 (range 5 days-14 months) and 12 months (range 5 days-58 months), respectively. Leptomeningeal disease was reported in 5 (9.6%) cases. CONCLUSION SCA directly followed by GKRS is an effective and time-efficient treatment for large cystic BM in selected patients in which surgery is contraindicated and those with deeply located lesions.
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30
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Suki D, Hatiboglu MA, Sawaya R. Evolution of Neurosurgical Treatment for Brain Metastases Over a 20-Year Period. Neurosurgery 2020. [DOI: 10.1093/neuros/nyaa304] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
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31
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Donovan EK, Greenspoon J, Schnarr KL, Whelan TJ, Wright JR, Hann C, Whitton A, Chow T, Parpia S, Swaminath A. A pilot study of stereotactic boost for malignant epidural spinal cord compression: clinical significance and initial dosimetric evaluation. Radiat Oncol 2020; 15:267. [PMID: 33208170 PMCID: PMC7672889 DOI: 10.1186/s13014-020-01710-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2020] [Accepted: 11/06/2020] [Indexed: 12/25/2022] Open
Abstract
Purpose Metastatic epidural spinal cord compression (MESCC) is a devastating complication of advanced malignancy, which can result in neurologic complications and significant deterioration in overall function and quality of life. Most patients are not candidates for optimal surgical decompression and as a result, receive urgent 3D conformal radiotherapy (3DCRT) to prevent or attempt to reverse neurologic progression. Multiple trials indicate that response and ambulatory rates after 3DCRT are inferior to surgery. The advent of stereotactic body radiation therapy (SBRT) has created a method with which a “radiosurgical decompression” boost may facilitate improve outcomes for MESCC patients. Methods We are conducting a pilot study to investigate SBRT boost after urgent 3D CRT for patients with MESCC. The aim of the study is to establish feasibility of this two-phase treatment regimen, and secondarily to characterize post-treatment ambulation status, motor response, pain control, quality of life and survival. Discussion We describe the study protocol and present a case report of one patient. A quality assurance review was conducted after the first seven patients, and resultant dose-constraints were revised to improve safety and feasibility of planning through more conservative organ at risk constraints. There have been no severe adverse events (grade 3–5) to date. We have illustrated clinical and dosimetric data of an example case, where a patient regained full strength and ambulatory capacity. Conclusions Our study aims to determine if SBRT is a feasible option in addition to standard 3DCRT for MESCC patients, with the goal to consider future randomized trials if successful. Having a robust quality assurance process in this study ensures translatability going forward if future trials with multicenter and increased patient representation are to be considered. Trial registration clinicaltrials.gov; registration no. NCT03529708; https://clinicaltrials.gov/ct2/show/NCT03529708; First posted May 18, 2018.
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Affiliation(s)
- Elysia K Donovan
- Sunnybrook Odette Cancer Centre, Department of Radiation Oncology, University of Toronto, 2075 Bayview Avenue, T2 Wing, Toronto, ON, M4N3M5, Canada
| | - Jeffrey Greenspoon
- Juravinski Cancer Centre, Department of Radiation Oncology, McMaster University, 3rd Floor, 699 Concession Street, Hamilton, ON, L8V 5C2, Canada
| | - Kara L Schnarr
- Juravinski Cancer Centre, Department of Radiation Oncology, McMaster University, 3rd Floor, 699 Concession Street, Hamilton, ON, L8V 5C2, Canada
| | - Timothy J Whelan
- Juravinski Cancer Centre, Department of Radiation Oncology, McMaster University, 3rd Floor, 699 Concession Street, Hamilton, ON, L8V 5C2, Canada
| | - James R Wright
- Juravinski Cancer Centre, Department of Radiation Oncology, McMaster University, 3rd Floor, 699 Concession Street, Hamilton, ON, L8V 5C2, Canada
| | - Crystal Hann
- Juravinski Cancer Centre, Department of Radiation Oncology, McMaster University, 3rd Floor, 699 Concession Street, Hamilton, ON, L8V 5C2, Canada
| | - Anthony Whitton
- Juravinski Cancer Centre, Department of Radiation Oncology, McMaster University, 3rd Floor, 699 Concession Street, Hamilton, ON, L8V 5C2, Canada
| | - Tom Chow
- Juravinski Cancer Centre, Department of Medical Physics, McMaster University, 4th Floor, 699 Concession Street, Hamilton, ON, L8V 5C2, Canada
| | - Sameer Parpia
- Juravinski Cancer Centre, Department of Oncology, McMaster University, 1st Floor, 699 Concession Street, Hamilton, ON, L8V 5C2, Canada
| | - Anand Swaminath
- Juravinski Cancer Centre, Department of Radiation Oncology, McMaster University, 3rd Floor, 699 Concession Street, Hamilton, ON, L8V 5C2, Canada.
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Wijetunga A, Jayamanne D, Cook R, Parkinson J, Little N, Curtis J, Brown C, Back M. Hypofractionated adjuvant surgical cavity radiotherapy following resection of limited brain metastasis. J Clin Neurosci 2020; 82:155-161. [PMID: 33317725 DOI: 10.1016/j.jocn.2020.10.041] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2020] [Revised: 09/09/2020] [Accepted: 10/18/2020] [Indexed: 12/26/2022]
Abstract
BACKGROUND Following surgical resection of oligometastatic disease to the brain there is a high rate of local relapse which is reduced by the addition of focal radiation therapy, often delivered as single fraction stereotactic radiosurgery (SRS) to the surgical cavity. This study audited the outcomes of an alternative approach using hypofractionated radiation therapy (HFRT) to the surgical resection cavity. METHODS AND MATERIALS Seventy-nine patients who received surgical resection and focal radiation therapy to the surgical cavity using HFRT with intensity modulated radiation therapy with or without stereotactic radiotherapy were identified. Doses were delivered in five fractions every second day for 10 days. Follow-up involved MRI surveillance with three-monthly MRI scans post resection. The major endpoints were local control at the surgical cavity site, and presence of radiation necrosis at the treated site. RESULTS Seventy-nine patients were included for the analysis with a median follow-up of 10.8 months. Of the cohort, 56% experienced intracranial progression, with all patients progressing distant to the resection cavity, and 7% progressing locally in addition. The one-year local control rate was 89.8%. The median progression-free survival was 10.0 months and median overall survival was 14.3 months. There was one CTCAE grade 3 toxicity of symptomatic radiation necrosis with no grade 4-5 toxicities seen. CONCLUSIONS The rate of local relapse following HFRT to the surgical cavity is low with minimal risk of radiation necrosis. HFRT can be considered as an alternative to SRS for focal radiotherapy after brain metastasis resection.
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Affiliation(s)
- A Wijetunga
- Sydney Medical School, Northern Clinical School, Reserve Road, St Leonards 2065, Australia.
| | - D Jayamanne
- Sydney Medical School, Northern Clinical School, Reserve Road, St Leonards 2065, Australia; Department of Radiation Oncology, Royal North Shore Hospital, Reserve Road, St Leonards 2065, Australia
| | - R Cook
- Department of Neurosurgery, Royal North Shore Hospital, Reserve Road, St Leonards 2065, Australia; The Brain Cancer Group, North Shore Private Hospital, Westbourne Street, St Leonards 2065, Australia
| | - J Parkinson
- Sydney Medical School, Northern Clinical School, Reserve Road, St Leonards 2065, Australia; Department of Neurosurgery, Royal North Shore Hospital, Reserve Road, St Leonards 2065, Australia; The Brain Cancer Group, North Shore Private Hospital, Westbourne Street, St Leonards 2065, Australia
| | - N Little
- Department of Neurosurgery, Royal North Shore Hospital, Reserve Road, St Leonards 2065, Australia
| | - J Curtis
- Department of Neurosurgery, Royal North Shore Hospital, Reserve Road, St Leonards 2065, Australia
| | - C Brown
- NHMRC Clinical Trials Centre, University of Sydney, 92-94 Parramatta Rd, Camperdown 2050, Australia
| | - M Back
- Sydney Medical School, Northern Clinical School, Reserve Road, St Leonards 2065, Australia; Department of Radiation Oncology, Royal North Shore Hospital, Reserve Road, St Leonards 2065, Australia; The Brain Cancer Group, North Shore Private Hospital, Westbourne Street, St Leonards 2065, Australia; Central Coast Cancer Centre, Gosford Hospital, Holden Street, Gosford 2250, Australia
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de Franca SA, Tavares WM, Salinet ASM, Teixeira MJ, Paiva WS. Laser interstitial thermal therapy as an adjunct therapy in brain tumors: A meta-analysis and comparison with stereotactic radiotherapy. Surg Neurol Int 2020; 11:360. [PMID: 33194293 PMCID: PMC7656052 DOI: 10.25259/sni_152_2020] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2020] [Accepted: 10/01/2020] [Indexed: 11/30/2022] Open
Abstract
BACKGROUND Minimally invasive procedures are gaining widespread acceptance in difficult-to-access brain tumor treatment. Stereotactic radiosurgery (SRS) is the preferred choice, however, laser interstitial thermal therapy (LITT) has emerged as a tumor cytoreduction technique. The present meta-analysis compared current SRS therapy with LITT in brain tumors. METHODS A search was performed in Lilacs, PubMed, and Cochrane database. Patient's demographics, tumor location, therapy used, Karnofsky performance status score before treatment, and patient's outcome (median overall survival, progression-free survival, and adverse events) data were extracted from studies. The risk of bias was assessed by Cochrane collaboration tool. RESULTS Twenty-five studies were included in this meta-analysis. LITT and SRS MOS in brain metastasis patients were 12.8 months' versus 9.8 months (ranges 9.3-16.3 and 8.3-9.8; P = 0.02), respectively. In a combined comparison of adverse effects among LITT versus SRS in brain metastasis, we found 15% reduction in absolute risk difference (-0.16; 95% confidence interval P < 0.0001). CONCLUSION We could not state that LITT treatment is an optimal alternative therapy for difficult-to-access brain tumors due to the lack of systematic data that were reported in our pooled studies. However, our results identified a positive effect in lowering the absolute risk of adverse events compared with SRS therapy. Therefore, randomized trials are encouraged to ascertain LITT role, as upfront or postoperative/post-SRS therapy for brain tumor treatment.
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Affiliation(s)
| | - Wagner Malago Tavares
- Department of Research, Instituto Paulista De Saude Para Alta Complexidade, Brazil
- Institute of Neurology, University of São Paulo, São Paulo, Brazil
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Tai P, Joseph K, Assouline A, Souied O, Leong N, Ferguson M, Yu E. Metastatic Brain Tumors: To Treat or Not to Treat, and with What? CURRENT CANCER THERAPY REVIEWS 2020. [DOI: 10.2174/1573394715666181211150849] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
A long time ago, metastatic brain tumors were often not treated and patients were only
given palliative care. In the past decade, researchers selected those with single or 1-3 metastases
for more aggressive treatments like surgical resection, and/or stereotactic radiosurgery (SRS),
since the addition of whole brain radiotherapy (WBRT) did not increase overall survival for the
vast majority of patients. Different studies demonstrated significantly less cognitive deterioration
in 0-52% patients after SRS versus 85-94% after WBRT at 6 months. WBRT is the treatment of
choice for leptomeningeal metastases. WBRT can lower the risk for further brain metastases, particularly
in tumors of fast brain metastasis velocity, i.e. quickly relapsing, often seen in melanoma
or small cell lung carcinoma. Important relevant literature is quoted to clarify the clinical controversies
at point of care in this review. Synchronous primary lung cancer and brain metastasis
represent a special situation whereby the oncologist should exercise discretion for curative treatments,
with reported 5-year survival rates of 7.6%-34.6%. Recent research suggests that those
patients with Karnofsky performance status less than 70, not capable of caring for themselves, are
less likely to derive benefit from aggressive treatments. Among patients with brain metastases
from non-small cell lung cancer (NSCLC), the QUARTZ trial (Quality of Life after Radiotherapy
for Brain Metastases) helps the oncologist to decide when not to treat, depending on the performance
status and other factors.
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Affiliation(s)
- Patricia Tai
- Allan Blair Cancer Center, University of Saskatchewan, Saskatoon, SK, Canada
| | - Kurian Joseph
- Cross Cancer Center, University of Alberta, Edmonton, AB, Canada
| | - Avi Assouline
- Centre Clinique de la Porte de Saint-Cloud, 30 Rue de Paris, 92100 Boulogne- Billancourt, France
| | - Osama Souied
- Allan Blair Cancer Center, University of Saskatchewan, Saskatoon, SK, Canada
| | - Nelson Leong
- Allan Blair Cancer Center, University of Saskatchewan, Saskatoon, SK, Canada
| | - Michelle Ferguson
- Allan Blair Cancer Center, University of Saskatchewan, Saskatoon, SK, Canada
| | - Edward Yu
- London Regional Cancer Program, Western University, London, ON, Canada
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Liu Z, He S, Li L. Comparison of Surgical Resection and Stereotactic Radiosurgery in the Initial Treatment of Brain Metastasis. Stereotact Funct Neurosurg 2020; 98:404-415. [PMID: 32898850 DOI: 10.1159/000509319] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2020] [Accepted: 06/09/2020] [Indexed: 01/11/2023]
Abstract
BACKGROUND Brain metastasis (BM) is the most common brain malignancy and a common cause of death in cancer patients. However, the relative outcome-related advantages and disadvantages of surgical resection (SR) and stereotactic radiosurgery (SRS) in the initial treatment of BM are controversial. METHOD We systematically reviewed the English language literature up to March 2020 to compare the efficacy of SR and SRS in the initial treatment of BM. We identified cohort studies from the Cochrane Library, PubMed, and EMBASE databases and conducted a meta-analysis following the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. Twenty cohort studies involving 1,809 patients were included. Local control did not significantly differ between the SR and SRS groups overall (hazard ratio [HR] 1.02, 95% confidence interval (CI) 0.64-1.64, p = 0.92; I2 = 54%, p = 0.03) or in subgroup analyses of SR plus SRS vs. SRS alone, SR plus whole brain radiation therapy (WBRT) versus SRS plus WBRT, or SR plus WBRT versus SRS alone. Distant intracranial control did not significantly differ between the SR and SRS groups overall (HR 0.78, 95% CI 0.38-1.60, p = 0.49; I2 = 61%, p = 0.03) or in subgroup analyses of SR plus SRS versus SRS alone or SR plus WBRT versus SRS alone. In addition, overall survival (OS) did not significantly differ in the SR and SRS groups (HR 0.91, 95% CI 0.65-1.27, p = 0.57; I2 = 47%, p = 0.09) or in subgroup analyses of SR plus SRS versus SRS alone, SR plus WBRT versus SRS alone or SR plus WBRT versus SRS plus WBRT. CONCLUSION Initial treatment of BM with SRS may offer comparable local and distant intracranial control to SR in patients with single or solitary BM. OS did not significantly differ between the SR and SRS groups in people with single or solitary BM.
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Affiliation(s)
- Zhen Liu
- Department of Neurosurgery, Peking University First Hospital, Beijing, China
| | - Shuting He
- Department of Anesthesiology, Peking University First Hospital, Beijing, China
| | - Liang Li
- Department of Neurosurgery, Peking University First Hospital, Beijing, China,
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Brain metastases of lung cancer: comparison of survival outcomes among whole brain radiotherapy, whole brain radiotherapy with consecutive boost, and simultaneous integrated boost. J Cancer Res Clin Oncol 2020; 147:569-577. [PMID: 32851477 DOI: 10.1007/s00432-020-03359-8] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2020] [Accepted: 08/18/2020] [Indexed: 10/23/2022]
Abstract
PURPOSE Radiotherapy is the mainstay for treating brain metastasis (BM). The objective of this study is to evaluate the overall survival (OS) of patients with BM of lung cancer treated with different radiotherapy modalities. METHODS Patients with BM of lung cancer who underwent radiotherapy between July 2007 and November 2017 were collected, and their baseline demographics, clinicopathological characteristics and treatments were recorded. Survival was estimated by the Kaplan-Meier method and compared by using the log-rank test. Univariate and multivariate analysis of the prognostic factors were performed using the Cox proportional hazard regression model. RESULTS A total of 144 patients were enrolled, of whom 77 underwent whole-brain radiotherapy (WBRT), 39 underwent whole brain radiotherapy with consecutive boost (WBRT + boost), and 28 underwent integrated simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT). The OS in SIB-IMRT group was significantly longer than that in WBRT group (median OS 14 (95% confidence interval [CI] 8.8-19.1) vs.7 (95% CI 5.5-8.5) months, log-rank p < 0.001) and WBRT + boost group (median OS: 14 (95% CI 8.8-19.1) vs.11 (95% CI 8.3-13.7) months, log-rank p = 0.037). Multivariable analysis showed that mortality risk of patients treated with SIB-IMRT decrease by 56, 59, 64 and 64% in unadjusted model (hazard ratio [HR] = 0.44; 95% CI 0.28-0.70, p < 0.001), model 1 (HR = 0.41; 95% CI 0.26-0.65, p < 0.001), model 2 (HR = 0.36; 95% CI 0.21-0.61, p < 0.001), and model 3 (HR = 0.36; 95% CI 0.21-0.61, p < 0.001). CONCLUSIONS For patients with BM of lung cancer, SIB-IMRT seems to be associated with a more favorable prognosis.
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Panagopoulos D, Karydakis P, Giakoumettis D, Themistocleous M. The 100 Most Cited Papers About Brain Metastases. World Neurosurg 2020; 138:98-114. [PMID: 32147557 DOI: 10.1016/j.wneu.2020.02.156] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2020] [Revised: 02/23/2020] [Accepted: 02/24/2020] [Indexed: 12/25/2022]
Abstract
BACKGROUND A vast amount of articles centered on brain metastases have been published. OBJECTIVE To present the 100 most-cited articles dedicated to brain metastasis and to accomplish a broad literature review. METHODS In December 2019, we performed a title-focused search using the Thomson Reuters Web of Science database to identify the most cited articles centered on brain metastatic disease. Our search query term was based on using the following algorithm: "brain metastases" OR "brain metastasis" OR "brain metastatic disease" OR "cerebral metastases" OR "cerebral metastasis" OR "cerebral metastatic disease." Afterward, we reviewed the results to certify that they were relevant to the purposes of our research protocol. The 100 most cited papers were chosen and further analyzed. RESULTS Our search resulted in 11,579 articles, published from 1975 until the completion of our survey. The most cited article, by Patchell et al., was published in 1990, with 1862 citations, and an average of 62.07 citations per year, whereas the last in our list, by Gaspar et al., was published in 2010, with 195 total citations, and an average of 19.50 citations per year. Countries with the highest-cited articles included the United States (75 records), followed by Canada (16 records). CONCLUSIONS We discovered the top 100 most-cited articles centered on brain metastasis, all of which show a potentially increased level of interest, because they are meaningful scientific reports. In addition, we reviewed the historical development and advances in brain metastasis research and relevant points of interest, alongside the relevant contributions of different authors, fields of special interest, and countries. Many of the most cited articles were written by authors whose specialty was not neurosurgery or by neurosurgeons who were supported by colleagues from other medical fields. As a consequence, many of these articles were not published in neurosurgery-dedicated journals.
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Affiliation(s)
- Dimitrios Panagopoulos
- Department of Neurosurgery, Pediatric Hospital of Athens, Goudi, Athens, Attica, Greece.
| | - Ploutarchos Karydakis
- Department of Neurosurgery, 251 Greek Air Force Hospital, Goudi, Athens, Attica, Greece
| | - Dimitrios Giakoumettis
- Department of Neurosurgery, Centre Hospitalier de Wallonie, Picarde-CHwapi A.S.B.L, Tournai, Belgium
| | - Marios Themistocleous
- Department of Neurosurgery, Pediatric Hospital of Athens, Goudi, Athens, Attica, Greece
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Remick JS, Kowalski E, Khairnar R, Sun K, Morse E, Cherng HRR, Poirier Y, Lamichhane N, Becker SJ, Chen S, Patel AN, Kwok Y, Nichols E, Mohindra P, Woodworth GF, Regine WF, Mishra MV. A multi-center analysis of single-fraction versus hypofractionated stereotactic radiosurgery for the treatment of brain metastasis. Radiat Oncol 2020; 15:128. [PMID: 32466775 PMCID: PMC7257186 DOI: 10.1186/s13014-020-01522-6] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2019] [Accepted: 03/24/2020] [Indexed: 12/22/2022] Open
Abstract
Background Hypofractionated-SRS (HF-SRS) may allow for improved local control and a reduced risk of radiation necrosis compared to single-fraction-SRS (SF-SRS). However, data comparing these two treatment approaches are limited. The purpose of this study was to compare clinical outcomes between SF-SRS versus HF-SRS across our multi-center academic network. Methods Patients treated with SF-SRS or HF-SRS for brain metastasis from 2013 to 2018 across 5 radiation oncology centers were retrospectively reviewed. SF-SRS dosing was standardized, whereas HF-SRS dosing regimens were variable. The co-primary endpoints of local control and radiation necrosis were estimated using the Kaplan Meier method. Multivariate analysis using Cox proportional hazards modeling was performed to evaluate the impact of select independent variables on the outcomes of interest. Propensity score adjustments were used to reduce the effects confounding variables. To assess dose response for HF-SRS, Biologic Effective Dose (BED) assuming an α/β of 10 (BED10) was used as a surrogate for total dose. Results One-hundred and fifty six patients with 335 brain metastasis treated with SF-SRS (n = 222 lesions) or HF-SRS (n = 113 lesions) were included. Prior whole brain radiation was given in 33% (n = 74) and 34% (n = 38) of lesions treated with SF-SRS and HF-SRS, respectively (p = 0.30). After a median follow up time of 12 months in each cohort, the adjusted 1-year rate of local control and incidence of radiation necrosis was 91% (95% CI 86–96%) and 85% (95% CI 75–95%) (p = 0.26) and 10% (95% CI 5–15%) and 7% (95% CI 0.1–14%) (p = 0.73) for SF-SRS and HF-SRS, respectively. For lesions > 2 cm, the adjusted 1 year local control was 97% (95% CI 84–100%) for SF-SRS and 64% (95% CI 43–85%) for HF-SRS (p = 0.06). On multivariate analysis, SRS fractionation was not associated with local control and only size ≤2 cm was associated with a decreased risk of developing radiation necrosis (HR 0.21; 95% CI 0.07–0.58, p < 0.01). For HF-SRS, 1 year local control was 100% for lesions treated with a BED10 ≥ 50 compared to 77% (95% CI 65–88%) for lesions that received a BED10 < 50 (p = 0.09). Conclusions In this comparison study of dose fractionation for the treatment of brain metastases, there was no difference in local control or radiation necrosis between HF-SRS and SF-SRS. For HF-SRS, a BED10 ≥ 50 may improve local control.
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Affiliation(s)
- Jill S Remick
- Department of Radiation Oncology, University of Maryland Medical Center, Baltimore, MD, USA
| | - Emily Kowalski
- Department of Radiation Oncology, University of Maryland Medical Center, Baltimore, MD, USA
| | - Rahul Khairnar
- Department of Pharmaceutical Health Services Research, University of Maryland School of Pharmacy, Baltimore, MD, USA
| | - Kai Sun
- Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Emily Morse
- Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Hua-Ren R Cherng
- Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Yannick Poirier
- Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Narottam Lamichhane
- Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Stewart J Becker
- Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Shifeng Chen
- Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Akshar N Patel
- Chesapeake Oncology Hematology Associates, Glen Bernie, MD, USA
| | - Young Kwok
- Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Elizabeth Nichols
- Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Pranshu Mohindra
- Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Graeme F Woodworth
- Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD, USA
| | - William F Regine
- Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Mark V Mishra
- Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD, USA.
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Abstract
OPINION STATEMENT With greater understanding of underlying biology and development of effective BRAF-targeted therapy and immunotherapy, along with remarkable advances in local treatment such as stereotactic radiosurgery, melanoma brain metastasis (MBM) is witnessing continually improving outcome, with 1-year overall survival rate approaching 85%. Given disease complexity and myriad treatment options, all patients with MBM should ideally be evaluated in a multidisciplinary setting to allow an individualized treatment approach based on prognostic groups, molecular classification, number and size of brain metastasis, and performance status. With improving outcome, pendulum has now swayed to focus more on effective treatment modalities with minimal neurological toxicity while maintaining quality of life. Surgery is usually considered in symptomatic and large MBMs, while stereotactic radiosurgery considered in 1-4 lesions, and now also being explored for up to 15 brain metastases for improved local control. The role of whole brain radiotherapy is diminishing given its neurocognitive toxicities and is reserved for patients with diffuse brain involvement. Cytotoxic chemotherapy has largely been ineffective without evidence for survival benefit. Immune checkpoint inhibitors have become the cornerstone of management for melanoma brain metastasis with durable intracranial tumor control and excellent toxicity profile. For patients with asymptomatic MBMs, ipilimumab and nivolumab have shown intracranial response near 60% and provides comparable clinical benefit in MBMs as for extracranial metastases. For patients with driver BRAF mutation, BRAFi-/MEKi-targeted agents are proven to be effective in MBM with high rate intracranial responses (44-59%). However, the durability of intracranial responses induced by BRAFi/MEKi seems to be shorter than that of extracranial disease. Emerging data support novel combination of systemic therapy and stereotactic radiosurgery, which appears to be safe and effective; however, potential benefits and risks should be evaluated prospectively. Promising ongoing trials will further expand therapeutic evidence in MBM, and patients should be encouraged to participate in clinical trials.
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Affiliation(s)
- Anupam Rishi
- Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, 12902 USF Magnolia Dr, Tampa, FL, 33612, USA
| | - Hsiang-Hsuan Michael Yu
- Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, 12902 USF Magnolia Dr, Tampa, FL, 33612, USA.
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Challenges in the treatment of breast cancer brain metastases: evidence, unresolved questions, and a practical algorithm. Clin Transl Oncol 2020; 22:1698-1709. [PMID: 32207041 DOI: 10.1007/s12094-020-02333-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2020] [Accepted: 03/01/2020] [Indexed: 12/24/2022]
Abstract
Breast cancer is the leading cause of brain metastases in women. Large randomized clinical trials that have evaluated local therapies in patients with brain metastases include patients with brain metastases from a variety of cancer types. The incidence of brain metastases in the breast cancer population continues to grow, which is, aside from the rising breast cancer incidence, mainly attributable to improvements in systemic therapies leading to more durable control of extracranial metastatic disease and prolonged survival. The management of breast cancer brain metastases remains challenging, even more so with the continued advancement of local and highly effective systemic therapies. For most patients, a metastases-directed initial approach (i.e., radiation, surgery) represents the most appropriate initial therapy. Treatment should be based on multidisciplinary team discussions and a shared decision with the patients taking into account the risks and benefits of each therapeutic modality with the goal of prolonging survival while maintaining quality of life. In this narrative review, a multidisciplinary group of experts will address challenging questions in the context of current scientific literature and propose a therapeutic algorithm for breast cancer patients with brain metastases.
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Loo M, Pin Y, Thierry A, Clavier JB. Single-fraction radiosurgery versus fractionated stereotactic radiotherapy in patients with brain metastases: a comparative study. Clin Exp Metastasis 2020; 37:425-434. [PMID: 32185576 DOI: 10.1007/s10585-020-10031-5] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2019] [Accepted: 03/10/2020] [Indexed: 12/11/2022]
Abstract
To compare the local control and brain radionecrosis in patients with brain metastasis primarily treated by single-fraction radiosurgery (SRS) or hypofractionated stereotactic radiotherapy (HFSRT). Between January 2012 and December 2017, 179 patients with only 1-3 brain metastases (total: 287) primarily treated by SRS (14 Gy) or HFSRT (23.1 Gy in 3 fractions of 7.7 Gy, every other day) were retrospectively analyzed in a single center. Follow-up imaging data were available in 152 patients with 246 lesions. The corresponding Biological Effective Dose (BED) were 33.6 Gy and 40.9 Gy respectively for SRS and HFSRT group, assuming an α/β of 10 Gy. Local control (LC) and risk of radionecrosis (RN) were calculated by the Kaplan-Meier method. The actuarial local control rates at 6 and 12 months were 94% and 88.1% in SRS group, and 87.6% and 78.4%, in HFSRT group (p = 0.06), respectively. Only the total volume of edema was associated with worse LC (p = 0.01, HR 1.02, 95% CI [1.004-1.03]) in multivariate analysis. Brain radionecrosis occurred in 1 lesion in SRS group and 9 in HFSRT group. Median time to necrosis was 5.5 months (range 1-9). Only the volume of GTV was associated with RN (p = 0.02, HR 1.09, 95% CI [1.01-1.18]) in multivariate analysis. Multi-fraction SRT dose of 23.31 Gy in 3 fractions has similar efficacy to single-fraction SRT dose of 14 Gy in patients with brain metastases. A slightly higher occurrence of radionecrosis appeared in HFSRT group.
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Affiliation(s)
- Maxime Loo
- Radiotherapy Department, Centre Paul Strauss, Strasbourg Cedex, 67065, France.
| | - Yvan Pin
- Radiotherapy Department, Centre Paul Strauss, Strasbourg Cedex, 67065, France
| | - Alicia Thierry
- Public Health and Statistics Department, Centre Paul Strauss, Strasbourg Cedex, 67065, France
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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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Churilla TM, Chowdhury IH, Handorf E, Collette L, Collette S, Dong Y, Alexander BM, Kocher M, Soffietti R, Claus EB, Weiss SE. Comparison of Local Control of Brain Metastases With Stereotactic Radiosurgery vs Surgical Resection: A Secondary Analysis of a Randomized Clinical Trial. JAMA Oncol 2019; 5:243-247. [PMID: 30419088 DOI: 10.1001/jamaoncol.2018.4610] [Citation(s) in RCA: 77] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Importance Brain metastases are a common source of morbidity for patients with cancer, and limited data exist to support the local therapeutic choice between surgical resection and stereotactic radiosurgery (SRS). Objective To evaluate local control of brain metastases among patients treated with SRS vs surgical resection within the European Organization for the Research and Treatment of Cancer (EORTC) 22952-26001 phase 3 trial. Design, Setting, and Participants This unplanned, exploratory analysis of the international, multi-institutional randomized clinical trial EORTC 22952-26001 (conducted from 1996-2007) was performed from February 9, 2017, through July 25, 2018. The EORTC 22952-26001 trial randomized patients with 1 to 3 brain metastases to whole-brain radiotherapy vs observation after complete surgical resection or before SRS. Patients in the present analysis were stratified but not randomized according to local modality (SRS or surgical resection) and treated per protocol with 1 to 2 brain metastases and tumors with a diameter of no greater than 4 cm. Interventions Surgical resection or SRS. Main Outcomes and Measures The primary end point was local recurrence of treated lesions. Cumulative incidence of local recurrence was calculated according to modality (surgical resection vs SRS) with competing risk regression to adjust for prognostic factors and competing risk of death. Results A total of 268 patients were included in the analysis (66.4% men; median age, 60.7 years [range, 26.9-81.1 years]); 154 (57.5%) underwent SRS and 114 (42.5%) underwent surgical resection. Median follow-up time was 39.9 months (range, 26.0-1982.0 months). Compared with the SRS group, patients undergoing surgical resection had larger metastases (median 28 mm [range, 10-40 mm] vs 20 mm [range, 4-40 mm]; P < .001), more frequently had 1 brain metastasis (112 [98.2%] vs 114 [74.0%]; P < .001), and differed in location (parietal, 21 [18.4%] vs 61 [39.6%]; posterior fossa, 30 [26.3%] vs 12 [7.8%]; P < .001). In adjusted models, local recurrence was similar between the SRS and surgical resection groups (hazard ratio [HR], 1.15; 95% CI, 0.72-1.83). However, when stratified by interval, patients with surgical resection had a much higher risk of early (0-3 months) local recurrence compared with those undergoing SRS (HR, 5.94; 95% CI, 1.72-20.45), but their risk decreased with time (HR for 3-6 months, 1.37 [95% CI, 0.64-2.90]; HR for 6-9 months, 0.75 [95% CI, 0.28-2.00]). At 9 months or longer, the surgical resection group had a lower risk of local recurrence (HR, 0.36; 95% CI, 0.14-0.93). Conclusions and Relevance In this exploratory analysis, local control of brain metastases was similar between SRS and surgical resection groups. Stereotactic radiosurgery was associated with improved early local control of treated lesions compared with surgical resection, although the relative benefit decreased with time. Trial Registration ClinicalTrials.gov Identifier: NCT00002899.
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Affiliation(s)
- Thomas M Churilla
- Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania
| | - Imran H Chowdhury
- Department of Radiation Oncology, Tufts Medical Center, Boston, Massachusetts
| | - Elizabeth Handorf
- Biostatistics and Bioinformatics Facility, Fox Chase Cancer Center, Philadelphia, Pennsylvania
| | | | | | - Yanqun Dong
- Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania
| | - Brian M Alexander
- Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts
| | - Martin Kocher
- Department of Stereotaxy and Functional Neurosurgery, University Hospital of Cologne, Cologne, Germany
| | - Riccardo Soffietti
- Department of Neuro-oncology, University of Turin and City of Health and Science Hospital, Torino, Italy
| | - Elizabeth B Claus
- Yale School of Public Health, New Haven, Connecticut.,Department of Neurosurgery, Brigham and Women's Hospital, Boston, Massachusetts
| | - Stephanie E Weiss
- Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania
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Sankey EW, Tsvankin V, Grabowski MM, Nayar G, Batich KA, Risman A, Champion CD, Salama AKS, Goodwin CR, Fecci PE. Operative and peri-operative considerations in the management of brain metastasis. Cancer Med 2019; 8:6809-6831. [PMID: 31568689 PMCID: PMC6853809 DOI: 10.1002/cam4.2577] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2019] [Revised: 09/07/2019] [Accepted: 09/09/2019] [Indexed: 12/24/2022] Open
Abstract
The number of patients who develop metastatic brain lesions is increasing as the diagnosis and treatment of systemic cancers continues to improve, resulting in longer patient survival. The role of surgery in the management of brain metastasis (BM), particularly multiple and recurrent metastases, remains controversial and continues to evolve. However, with appropriate patient selection, outcomes after surgery are typically favorable. In addition, surgery is the only means to obtain a tissue diagnosis and is the only effective treatment modality to quickly relieve neurological complications or life-threatening symptoms related to significant mass effect, CSF obstruction, and peritumoral edema. As such, a thorough understanding of the role of surgery in patients with metastatic brain lesions, as well as the factors associated with surgical outcomes, is essential for the effective management of this unique and growing patient population.
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Affiliation(s)
- Eric W. Sankey
- Department of NeurosurgeryDuke University Medical CenterDurhamNCUSA
| | - Vadim Tsvankin
- Department of NeurosurgeryDuke University Medical CenterDurhamNCUSA
| | | | - Gautam Nayar
- Department of NeurosurgeryUniversity of Pittsburgh Medical CenterPittsburghPAUSA
| | | | - Aida Risman
- School of MedicineMedical College of GeorgiaAugustaGAUSA
| | | | | | - C. Rory Goodwin
- Department of NeurosurgeryDuke University Medical CenterDurhamNCUSA
| | - Peter E. Fecci
- Department of NeurosurgeryDuke University Medical CenterDurhamNCUSA
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Couñago F, Luna J, Guerrero LL, Vaquero B, Guillén-Sacoto MC, González-Merino T, Taboada B, Díaz V, Rubio-Viqueira B, Díaz-Gavela AA, Marcos FJ, del Cerro E. Management of oligometastatic non-small cell lung cancer patients: Current controversies and future directions. World J Clin Oncol 2019; 10:318-339. [PMID: 31799148 PMCID: PMC6885452 DOI: 10.5306/wjco.v10.i10.318] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2019] [Revised: 08/30/2019] [Accepted: 09/13/2019] [Indexed: 02/06/2023] Open
Abstract
Oligometastatic non-small cell lung cancer (NSCLC) describes an intermediate stage of NSCLC between localized and widely-disseminated disease. This stage of NSCLC is characterized by a limited number of metastases and a more indolent tumor biology. Currently, the management of oligometastatic NSCLC involves radical treatment (radiotherapy or surgery) that targets the metastatic lesions and the primary tumor to achieve disease control. This approach offers the potential to achieve prolonged survival in patients who, in the past, would have only received palliative measures. The optimal therapeutic strategies for the different scenarios of oligometastatic disease (intracranial vs extracranial disease, synchronous vs metachronous) remain undefined. Given the lack of head-to-head studies comparing radiotherapy to surgery in these patients, the decision to apply surgery or radiotherapy (with or without systemic treatment) must be based on prognostic factors that allow us to classify patients. This classification will allow us to select the most appropriate therapeutic strategy on an individualized basis. In the future, the molecular or microRNA profiles will likely improve the treatment selection process. The objective of the present article is to review the most relevant scientific evidence on the management of patients with oligometastatic NSCLC, focusing on the role of radiotherapy and surgery. We also discuss areas of controversy and future directions.
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Affiliation(s)
- Felipe Couñago
- Department of Radiation Oncology, Hospital Universitario Quirónsalud Madrid, Pozuelo de Alarcón, Madrid 28223, Spain
- Department of Radiation Oncology, Hospital La Luz, Madrid 28003, Spain
- Clinical Department, Faculty of Biomedicine, Universidad Europea, Madrid 28223, Spain
| | - Javier Luna
- Department of Radiation Oncology, Hospital Fundación Jiménez Díaz, Madrid 28040, Spain
| | | | - Blanca Vaquero
- Department of Radiation Oncology, Hospital La Luz, Madrid 28003, Spain
| | | | | | - Begoña Taboada
- Department of Radiation Oncology, Complexo Hospitalario Universitario Santiago de Compostela, Santiago de Compostela 15706, Spain
| | - Verónica Díaz
- Department of Radiation Oncology, Hospital Universitario Puerta del Mar, Cádiz 11009, Spain
| | - Belén Rubio-Viqueira
- Department of Medical Oncology, Hospital Universitario Quirónsalud Madrid, Pozuelo de Alarcón, Madrid 28223, Spain
| | - Ana Aurora Díaz-Gavela
- Department of Radiation Oncology, Hospital Universitario Quirónsalud Madrid, Pozuelo de Alarcón, Madrid 28223, Spain
- Department of Radiation Oncology, Hospital La Luz, Madrid 28003, Spain
- Clinical Department, Faculty of Biomedicine, Universidad Europea, Madrid 28223, Spain
| | - Francisco José Marcos
- Department of Radiation Oncology, Hospital Universitario Quirónsalud Madrid, Pozuelo de Alarcón, Madrid 28223, Spain
- Department of Radiation Oncology, Hospital La Luz, Madrid 28003, Spain
- Clinical Department, Faculty of Biomedicine, Universidad Europea, Madrid 28223, Spain
| | - Elia del Cerro
- Department of Radiation Oncology, Hospital Universitario Quirónsalud Madrid, Pozuelo de Alarcón, Madrid 28223, Spain
- Department of Radiation Oncology, Hospital La Luz, Madrid 28003, Spain
- Clinical Department, Faculty of Biomedicine, Universidad Europea, Madrid 28223, Spain
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Yuan M, Behrami E, Pannullo S, Schwartz TH, Wernicke AG. The Relationship Between Tumor Volume and Timing of Post-resection Stereotactic Radiosurgery to Maximize Local Control: A Critical Review. Cureus 2019; 11:e5762. [PMID: 31723521 PMCID: PMC6825444 DOI: 10.7759/cureus.5762] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
After maximally safe neurosurgical resection of brain metastases, stereotactic radiosurgery (SRS) is now recommended as an alternative to whole-brain radiation therapy (WBRT), which has been associated with cognitive decline. One complicating factor associated with SRS is that postoperative cavity dynamics can change dramatically, creating significant variability in the recommended timing of SRS. While SRS has been shown to improve local control (LC) in smaller tumor cavities, achieving excellent LC rates still remains a challenge in larger ones. Furthermore, factors predicting the optimal timing of SRS in relation to the cavity size need to be defined and implemented. Variables such as the delay between postoperative MRI and treatment are critical but poorly understood. One potential treatment option that may improve outcomes is brachytherapy, but the widespread implementation of this technique has been slow. This critical review analyzes the relationship between preoperative tumor volume, resection cavity size, and timing of SRS and explores how these variables must be understood in order to achieve the highest LC possible.
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Affiliation(s)
- Melissa Yuan
- Neurological Surgery, NewYork-Presbyterian/Weill Cornell Medical Center, New York, USA
| | - Eltion Behrami
- Radiation Oncology, NewYork-Presbyterian/Weill Cornell Medical Center, New York, USA
| | - Susan Pannullo
- Neurological Surgery, NewYork-Presbyterian/Weill Cornell Medical Center, New York, USA
| | | | - A Gabriella Wernicke
- Radiation Oncology, NewYork-Presbyterian/Weill Cornell Medical Center, New York, USA
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Michaelidesová A, Konířová J, Bartůněk P, Zíková M. Effects of Radiation Therapy on Neural Stem Cells. Genes (Basel) 2019; 10:E640. [PMID: 31450566 PMCID: PMC6770913 DOI: 10.3390/genes10090640] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2019] [Revised: 08/19/2019] [Accepted: 08/22/2019] [Indexed: 12/29/2022] Open
Abstract
Brain and nervous system cancers in children represent the second most common neoplasia after leukemia. Radiotherapy plays a significant role in cancer treatment; however, the use of such therapy is not without devastating side effects. The impact of radiation-induced damage to the brain is multifactorial, but the damage to neural stem cell populations seems to play a key role. The brain contains pools of regenerative neural stem cells that reside in specialized neurogenic niches and can generate new neurons. In this review, we describe the advances in radiotherapy techniques that protect neural stem cell compartments, and subsequently limit and prevent the occurrence and development of side effects. We also summarize the current knowledge about neural stem cells and the molecular mechanisms underlying changes in neural stem cell niches after brain radiotherapy. Strategies used to minimize radiation-related damages, as well as new challenges in the treatment of brain tumors are also discussed.
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Affiliation(s)
- Anna Michaelidesová
- Laboratory of Cell Differentiation, Institute of Molecular Genetics of the Czech Academy of Sciences, v. v. i., Vídeňská 1083, 142 20 Prague 4, Czech Republic
- Department of Radiation Dosimentry, Nuclear Physics Institute of the Czech Academy of Sciences, v. v. i., Na Truhlářce 39/64, 180 00 Prague 8, Czech Republic
| | - Jana Konířová
- Laboratory of Cell Differentiation, Institute of Molecular Genetics of the Czech Academy of Sciences, v. v. i., Vídeňská 1083, 142 20 Prague 4, Czech Republic
- Department of Radiation Dosimentry, Nuclear Physics Institute of the Czech Academy of Sciences, v. v. i., Na Truhlářce 39/64, 180 00 Prague 8, Czech Republic
| | - Petr Bartůněk
- Laboratory of Cell Differentiation, Institute of Molecular Genetics of the Czech Academy of Sciences, v. v. i., Vídeňská 1083, 142 20 Prague 4, Czech Republic
| | - Martina Zíková
- Laboratory of Cell Differentiation, Institute of Molecular Genetics of the Czech Academy of Sciences, v. v. i., Vídeňská 1083, 142 20 Prague 4, Czech Republic.
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Ayandipo OO, Adeleye AO, Ulasi IB, Ogundiran TO. Outcome of Cerebral Metastasectomy in Select Cases of Brain Metastases from Breast Cancer in Ibadan, Nigeria. World Neurosurg 2019; 127:186-193. [PMID: 30954731 DOI: 10.1016/j.wneu.2019.03.279] [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: 01/03/2019] [Revised: 03/27/2019] [Accepted: 03/28/2019] [Indexed: 10/27/2022]
Abstract
BACKGROUND Brain metastasis (BM) from breast cancer is increasingly encountered clinically because of the continuing success in the oncological control of the primary disease. Data-driven reports on the surgical treatment of BM from breast cancer are sparse in sub-Saharan Africa. METHODS This is a prospective cohort study of the outcome of surgical excision of BM from breast cancer in an academic surgical practice in Ibadan, Nigeria. RESULTS A total of 12 consecutive cerebral metastasectomies, all in females with primary breast cancer, were recorded over the study period. The median age (range) at breast cancer diagnosis was 41 (27-72) years, and the time interval from primary disease to BM was 19 (12-29) months. The BM was the first site of systemic disease progression in all, and was heralded by headache, seizures, and hemiparesis in more than two-thirds of the patients. The brain lesions were multiple in a quarter: >4 cm large in 42% and were located supratentorial in >80%. They all achieved good recovery and in-hospital outcome after surgical lesionectomy-infra- and supratentorial craniotomies-but only two-thirds could access postsurgical adjuvant whole brain radiation therapy. Median survival after cerebral metastasectomy was 18 (11-55) months, and more than a quarter were alive for ≥3years. These survival statistics were significantly better than those of a contemporary cohort of our patients with breast cancer who also had BMs that were not surgically treated for various clinical and logistic limitations. CONCLUSIONS Surgical resection is feasible for BM from breast cancer even in low-resource clinical practice. It has a salutary effect on the patients' quality of life.
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Affiliation(s)
- Omobolaji Oladayo Ayandipo
- Division of Oncological Surgery, Department of Surgery, College of Medicine, University of Ibadan/University College Hospital Ibadan, Ibadan, Nigeria
| | - Amos Olufemi Adeleye
- Division of Neurological Surgery, Department of Surgery, College of Medicine, University of Ibadan/University College Hospital Ibadan, Ibadan, Nigeria.
| | | | - Temidayo Olusade Ogundiran
- Division of Oncological Surgery, Department of Surgery, College of Medicine, University of Ibadan/University College Hospital Ibadan, Ibadan, Nigeria
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Faramand A, Niranjan A, Kano H, Flickinger J, Lunsford LD. Primary or salvage stereotactic radiosurgery for brain metastatic small cell lung cancer. J Neurooncol 2019; 144:217-225. [PMID: 31230250 DOI: 10.1007/s11060-019-03224-w] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2019] [Accepted: 06/16/2019] [Indexed: 01/30/2023]
Abstract
PURPOSE We evaluated the outcomes after stereotactic radiosurgery (SRS) for patients who developed new or progressive brain disease regardless of whether they had no prior radiation, PCI, or WBRT. METHODS We retrospectively identified 90 SCLC patients who had SRS between 1991 and 2018. Thirty-one patients had no evidence of brain disease at the time of initial diagnosis but received prophylactic cranial irradiation. Twenty-six without initial brain disease underwent delayed SRS after brain disease was identified. Seventeen patients with synchronous systemic and brain disease underwent WBRT at the time of diagnosis. Fifteen patients had brain disease detected at the time of initial diagnosis and had initial SRS. RESULTS We found no difference in overall survival between patients who received initial PCI or WBRT compared to patients treated with SRS alone at the time when brain metastases were identified. PCI was not associated with a longer duration between initial diagnosis and the development of brain metastasis. Local tumor control was achieved in 49 out of 58 patients who had follow up MRI available for review (84.5%). Actuarial local tumor control at 3, 6, and 12 months was calculated as 92%, 85%, and 80%, respectively. Radiation therapy (PCI or WBRT) before SRS was not associated with better or worse local tumor control. CONCLUSION In this experience neither prior PCI nor WBRT improved survival or local tumor control in SCLC patients who underwent SRS for new or recurrent brain disease.
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Affiliation(s)
- Andrew Faramand
- Department of Neurosurgery and Radiation Oncology, University of Pittsburgh Medical Center, Pittsburgh, USA.
- Department of Neurological Surgery, University of Pittsburgh, Suit B-400, UPMC Presbyterian, 200 Lothrop St, Pittsburgh, PA, 15213, USA.
| | - Ajay Niranjan
- Department of Neurosurgery and Radiation Oncology, University of Pittsburgh Medical Center, Pittsburgh, USA
| | - Hideyuki Kano
- Department of Neurosurgery and Radiation Oncology, University of Pittsburgh Medical Center, Pittsburgh, USA
| | - John Flickinger
- Department of Neurosurgery and Radiation Oncology, University of Pittsburgh Medical Center, Pittsburgh, USA
| | - L Dade Lunsford
- Department of Neurosurgery and Radiation Oncology, University of Pittsburgh Medical Center, Pittsburgh, USA
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50
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Outcome after surgery in supratentorial and infratentorial solitary brain metastasis. Acta Neurochir (Wien) 2019; 161:1047-1053. [PMID: 30859322 DOI: 10.1007/s00701-019-03865-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2018] [Accepted: 03/03/2019] [Indexed: 01/06/2023]
Abstract
BACKGROUND The aim of this retrospective study was to investigate and compare the outcome after surgery in patients with a supratentorial solitary metastasis (SSM) and an infratentorial solitary metastasis (ISM). A worse prognosis has been reported in ISM. METHODS Fifty-two patients with a newly diagnosed solitary brain metastasis on MRI were included to identify risk factors affecting the outcome. Key variables included tumor size, staging of the primary tumor, time span of presurgical work-up, and surgical technique. Outcome variables included postoperative complications, tumor recurrence, and mortality. Kaplan-Meier survival analysis was applied. RESULTS Thirty patients with a SSM and 22 patients with an ISM underwent gross total resection. The tumor size did not have a statistical significant effect on survival. Presurgical work-up time was similar in SSM and ISM. Postoperative complications were more frequently encountered in ISM. Recurrence rate was comparable in SSM and ISM. Carcinomatous meningitis (CM) was more frequently seen in ISM, and CM was seen more often with the piecemeal resection technique. There was no statistical difference in overall survival between SSM and ISM. CONCLUSIONS This study identified factors that play a role in the outcome after surgery in patients with ISM and SSM on MRI. Postoperative complications seemed to be higher in ISM and CM was more often seen in ISM, but the worse prognosis in patients with ISM compared with SSM could not be confirmed.
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