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Şenkesen Ö, Ispir EB, Göksel EO, Akdeniz Y. Dosimetric comparison of advanced radiotherapy planning techniques for hippocampal sparing whole brain radiotherapy. Cancer Radiother 2025; 29:104643. [PMID: 40398377 DOI: 10.1016/j.canrad.2025.104643] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2025] [Revised: 05/03/2025] [Accepted: 05/05/2025] [Indexed: 05/23/2025]
Abstract
PURPOSE Hippocampal-sparing whole-brain radiotherapy aims to reduce neurocognitive decline in patients receiving cranial irradiation. Advances in radiotherapy planning systems offer improved sparing of organs at risk while maintaining target coverage. This study compared the dosimetric performance of five planning techniques for hippocampal-sparing whole-brain radiotherapy: Radixact with 1cm and 2.5cm field widths, Ethos, HyperArc, and volumetric modulated arctherapy using advanced optimization algorithms. MATERIALS AND METHODS Eleven patients who underwent whole brain irradiation were included in this retrospective planning study. The prescribed dose was 30Gy in 12 fractions, with hippocampus dose constraints of D98 %≤9Gy and D2 %≤17Gy. Radixact plans were created using the VOLO™ Ultra optimizer with normal tissue objective parameters for dose fall-off control. Ethos plans were generated using an intelligent optimization engine with automated planning. HyperArc employed four non-coplanar arcs with SRS normal tissue objective optimization, while volumetric modulated arctherapy utilized six arcs. Dosimetric parameters, including planning target volume coverage, hippocampal doses, and organs at risk constraints, were analyzed using one-way ANOVA. RESULTS Radixact with 1cm field width achieved the lowest hippocampal doses, whereas HyperArc and volumetric modulated arctherapy provided superior planning target volume coverage. Ethos resulted in the lowest doses to organs at risk, while HyperArc had the shortest treatment duration. Statistically significant differences (P<0.05) were observed across techniques for hippocampal D98 %, D2 %, and sparing of organs at risk. CONCLUSION Advanced planning techniques offer distinct dosimetric advantages for hippocampal-sparing whole-brain radiotherapy. Radixact with 1cm field width optimally spares the hippocampus, while HyperArc and volumetric modulated arctherapy balance sparing of organs at risk with shorter treatment times. Selection of an optimal planning approach should consider both dosimetric outcomes and clinical workflow efficiency.
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Affiliation(s)
- Öznur Şenkesen
- Acıbadem Mehmet Ali Aydınlar University, Istanbul, Turkey; Department of Radiation Oncology, Acıbadem Ataşehir Hospital, Istanbul, Turkey.
| | - Emine Burçin Ispir
- Department of Radiation Oncology, Acıbadem Ataşehir Hospital, Istanbul, Turkey
| | - Evren Ozan Göksel
- Acıbadem Mehmet Ali Aydınlar University, Istanbul, Turkey; Department of Radiation Oncology, Acıbadem Altunizade Hospital, Istanbul, Turkey
| | - Yücel Akdeniz
- Department of Radiation Oncology, Acıbadem Adana Hospital, Istanbul, Turkey
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Gutiérrez-García B, Cáceres CM, Núñez-Marín F, Molero J, Prats L, Mestre N, Martínez S, Teixidor P, Comas S, Balañà C, Villà S. Early region-specific impact of adjuvant radiation therapy on cognition and quality of life in adult patients with primary brain tumors. Clin Transl Oncol 2025; 27:2143-2159. [PMID: 39367900 DOI: 10.1007/s12094-024-03740-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: 08/29/2024] [Accepted: 09/16/2024] [Indexed: 10/07/2024]
Abstract
PURPOSE While treatments for primary brain tumors increase survival, they have cognitive sequelae. Neurocognition's anatomical distribution makes it susceptible to brain damage. This study aims to evaluate the contribution of radiotherapy on short-term cognitive impairment. METHODS/PATIENTS Using a prospective database of cognitive rehabilitation in adults operated on for primary brain tumors, a retrospective sub-analysis of the contribution of radiotherapy was performed. Thirty-four subdivisions of 12 neurocognitive regions were delineated in 48 irradiated patients and 30 non-irradiated patients. In the first group, the correlation between radiation dose and deterioration was evaluated. In all patients, the impact of tumor and surgical changes on dysfunction was calculated and compared with dose-dependent response. RESULTS The correlation between cognitive status and radiation dose is especially strong and significant in the left hemisphere and in specific subdivisions such as the posterior hippocampus or the dorsolateral prefrontal cortex, with the left prevailing over posterior dominance. Memory is the most affected domain 1 month after radiotherapy, as attention is three months later. The hippocampus is involved in various cognitive domains in addition to memory. The prefrontal subregions and the genu of the corpus callosum are more affected by the relationship with disease and surgical changes than by radiation exposure. Patients ongoing a course of radiotherapy do not benefit from concurrent cognitive rehabilitation. CONCLUSIONS There is a correlation between the dose of radiation received by several encephalic regions and degree of short-term domain-specific cognition decline, considering other factors of risk and cognitive rehabilitation.
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Affiliation(s)
- Beatriz Gutiérrez-García
- Radiation Oncology, Institut Català d'Oncologia, Hospital Universitari Germans Trias i Pujol, Badalona, Spain.
| | - Cynthia M Cáceres
- Neuropsychology, Hospital Universitari Germans Trias i Pujol, Badalona, Spain
| | | | - Jaume Molero
- Radiophysics and Radiological Protection, Institut Català d'Oncologia, Hospital Universitari Germans Trias i Pujol, Badalona, Spain
| | - Lluis Prats
- Radiophysics and Radiological Protection, Institut Català d'Oncologia, Hospital Universitari Germans Trias i Pujol, Badalona, Spain
| | - Neus Mestre
- Biostatistics, Centro de Regulación Genómica, Barcelona, Spain
| | - Silvia Martínez
- Neuropsychology, Hospital Universitari Germans Trias i Pujol, Badalona, Spain
| | - Pilar Teixidor
- Neurosurgery, Hospital Universitari Germans Trias i Pujol, Badalona, Spain
| | - Silvia Comas
- Radiation Oncology, Institut Català d'Oncologia, Hospital Universitari Germans Trias i Pujol, Badalona, Spain
| | - Carme Balañà
- Medical Oncology, Institut Català d'Oncologia, Hospital Universitari Germans Trias i Pujol, Badalona, Spain
| | - Salvador Villà
- Radiation Oncology, Institut Català d'Oncologia, Hospital Universitari Germans Trias i Pujol, Badalona, Spain
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Ryu H, Li X, Lee TH, Kim TM, Choi SH, Park CK, Lee ST, Park SH, Won JK, Jang BS, Kim IH, Lee JH. Distribution and failure patterns of primary central nervous system lymphoma related to the hippocampus: implications for hippocampal avoidance irradiation. J Neurooncol 2025; 173:95-104. [PMID: 39969784 PMCID: PMC12041158 DOI: 10.1007/s11060-025-04965-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2025] [Accepted: 02/04/2025] [Indexed: 02/20/2025]
Abstract
PURPOSE Hippocampal injury from WBRT contributes to neurocognitive decline in brain malignancy patients. HA-WBRT may mitigate this by reducing hippocampal radiation exposure, but its feasibility in PCNSL remains unassessed regarding hippocampal involvement and failure rates. This study evaluates hippocampal involvement at diagnosis and after treatment in PCNSL patients. MATERIALS AND METHODS We conducted a retrospective analysis of 278 immunocompetent PCNSL patients diagnosed between 2000 and 2021. Following high-dose methotrexate-based induction chemotherapy, patients either received consolidation therapy, including RT, cytarabine alone, or autologous stem cell transplantation or underwent observation. Hippocampus was outlined on T1 MRI images and expanded by a 5 mm margin to create the hippocampal avoidance region (HAR). Hippocampal failure was defined as recurrence or progression at HAR. The median follow-up was 38.7 months (range 3.1-239.4 months). RESULTS Of the 278 patients diagnosed with PCNSL, 39.9% presented initial lesions at HAR. After induction therapy, 212 evaluable patients received consolidation treatments or observation. Intracranial failures occurred in 47.6% (n = 101), with 66.3% (n = 67) occurring outside the HAR and 33.7% (n = 34) inside the HAR. Unifocal disease (HR 0.61, 95% CI 0.39-0.96, p = 0.025) was associated with a lower risk of hippocampal failures, while initial HAR involvement significantly increased the risk (HR 2.26, 95% CI 1.18-4.47, p = 0.018). Patients with unifocal disease outside the HAR had the lowest 3-year hippocampal failure rate (6.2%). RT that included the hippocampus did not significantly affect hippocampal failure rates in patients without initial HAR lesions (p = 0.282), with three-year rates of 9.2 vs. 14.6% for other treatments. However, among patients with initial HAR involvement, RT including the hippocampus significantly reduced hippocampal failure rates compared to other approaches (p = 0.002). Hippocampal failure rates were comparable, with conventional WBRT at 14.6% and HA-WBRT at 19% in patients without initial HAR lesions (p = 0.734). CONCLUSION The routine application of the HA-WBRT strategy is not supported due to the high risk of hippocampal failures in general and requires further investigation to establish its feasibility and safety in well-defined subgroups. Our results suggest that the HA-WBRT strategy could be evaluated for select PCNSL patients with unifocal lesions or those located outside the HAR.
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Affiliation(s)
- Hyejo Ryu
- Department of Radiation Oncology, Chung-Ang University Gwangmyeong Hospital, Gwangmyeong, Gyeonggii-Do, Republic of Korea
- Department of Radiation Oncology, Seoul National University Hospital, Seoul National University College of Medicine, 101 Daehak-Ro, Jongno-Gu, Seoul, 03080, Republic of Korea
| | - Xue Li
- Department of Radiation Oncology, Seoul National University Hospital, Seoul National University College of Medicine, 101 Daehak-Ro, Jongno-Gu, Seoul, 03080, Republic of Korea
- Department of Radiation Oncology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, People's Republic of China
- Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
- Institute of Radiation Medicine, Medical Research Center, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Tae Hoon Lee
- Department of Radiation Oncology, Seoul National University Hospital, Seoul National University College of Medicine, 101 Daehak-Ro, Jongno-Gu, Seoul, 03080, Republic of Korea
- Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Tae Min Kim
- Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Seung Hong Choi
- Department of Radiology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Chul-Kee Park
- Department of Neurosurgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Soon Tae Lee
- Department of Neurology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Sung-Hye Park
- Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Jae-Kyung Won
- Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Bum-Sup Jang
- Department of Radiation Oncology, Seoul National University Hospital, Seoul National University College of Medicine, 101 Daehak-Ro, Jongno-Gu, Seoul, 03080, Republic of Korea
| | - Il Han Kim
- Department of Radiation Oncology, Seoul National University Hospital, Seoul National University College of Medicine, 101 Daehak-Ro, Jongno-Gu, Seoul, 03080, Republic of Korea
| | - Joo Ho Lee
- Department of Radiation Oncology, Seoul National University Hospital, Seoul National University College of Medicine, 101 Daehak-Ro, Jongno-Gu, Seoul, 03080, Republic of Korea.
- Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
- Institute of Radiation Medicine, Medical Research Center, Seoul National University College of Medicine, Seoul, Republic of Korea.
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Tari SY, Heikal A, Le C, Yang F, Dinakaran D, Amanie J, Murtha A, Rowe LS, Roa WH, Patel S. Left hippocampus sparing model for glioblastoma radiotherapy by utilizing knowledge-based planning and multi-criteria optimization. J Appl Clin Med Phys 2025; 26:e70014. [PMID: 39955265 PMCID: PMC12059297 DOI: 10.1002/acm2.70014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2024] [Revised: 09/21/2024] [Accepted: 12/03/2024] [Indexed: 02/17/2025] Open
Abstract
PURPOSE Results of a prospective, randomized controlled trial at our institute demonstrate an association between the dose to the left hippocampus and neurocognitive decline post-radiotherapy for patients with glioblastoma. To minimize the dose to the left hippocampus, a left hippocampus sparing model was created using RapidPlan (RP) and multi-criteria optimization (MCO). MATERIALS AND METHODS For 147 patients with newly diagnosed glioblastoma treated with volumetric modulated arc therapy (VMAT), the left and right hippocampus were delineated. Ninety-seven of 147 VMAT plans were used to configure a RP model named HCS1. The remaining 50 VMAT plans were used for the model validation. All 97 plans were replanned with the HCS1 and further optimized using MCO (HCS1+MCO). MCO was used to explore the trade-off between reducing the left hippocampus mean dose and planning objectives for the targets and other organs-at-risk (OAR) for HCS1 plans. These plans were used to create a new model called HCS2. MCO and RP model configuration were done within the Eclipse treatment planning system. RESULTS The final HCS2 model decreased the mean dose to the left hippocampus by 26% compared to clinically treated plans without reducing target coverage for 50 validation data. The mean dose to the left hippocampus decreased from 32.65 Gy in clinically treated plans, 30.45 Gy in HCS1-generated plans, and 24.04 Gy in HCS2-generated plans. The mean volume receiving 95% of the prescription dose (V95%) of the planning target volume was 99.08% ± 1.39% in clinically treated plans, 99.03% ± 1.37% in HCS1-generated plans, and 98.80% ± 1.48% in HCS2-generated plans. Mean dose to 0.1 cc of the brainstem improved from 45.91 Gy in clinically treated plans to 39.29 Gy in HCS2-generated plans. CONCLUSIONS The RP model and MCO helps to decrease left hippocampus mean dose while maintaining the target volume coverage and OAR sparing comparable to clinically treated plans for glioblastoma patients.
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Affiliation(s)
- Shima Y. Tari
- Department of Medical PhysicsCross Cancer InstituteEdmontonAlbertaCanada
- Department of OncologyDivision of Medical PhysicsUniversity of AlbertaEdmontonAlbertaCanada
| | - Amr Heikal
- Department of Medical PhysicsCross Cancer InstituteEdmontonAlbertaCanada
- Department of OncologyDivision of Medical PhysicsUniversity of AlbertaEdmontonAlbertaCanada
| | - Connie Le
- Division of Radiation OncologyDepartment of OncologyUniversity of AlbertaEdmontonAlbertaCanada
| | - Fan Yang
- Division of Radiation OncologyDepartment of OncologyUniversity of AlbertaEdmontonAlbertaCanada
- Present address:
Mayo ClinicDepartment of Radiation OncologyPhoenixAZUSA
| | - Deepak Dinakaran
- Division of Radiation OncologyDepartment of OncologyUniversity of AlbertaEdmontonAlbertaCanada
- Present address:
Sunnybrook Health Science CenterDepartment of Radiation OncologyTorontoOntarioCanada
| | - John Amanie
- Division of Radiation OncologyDepartment of OncologyUniversity of AlbertaEdmontonAlbertaCanada
| | - Albert Murtha
- Division of Radiation OncologyDepartment of OncologyUniversity of AlbertaEdmontonAlbertaCanada
| | - Lindsay S. Rowe
- Division of Radiation OncologyDepartment of OncologyUniversity of AlbertaEdmontonAlbertaCanada
| | - Wilson H. Roa
- Division of Radiation OncologyDepartment of OncologyUniversity of AlbertaEdmontonAlbertaCanada
| | - Samir Patel
- Division of Radiation OncologyDepartment of OncologyUniversity of AlbertaEdmontonAlbertaCanada
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Mireștean CC, Buzea CG, Zară AD, Iancu RI, Iancu DPT. Potential Risk of Cognitive Impairment Due to Irradiation of Neural Structures in Locally Advanced Nasopharyngeal Cancer Treated by Curative Radiotherapy. MEDICINA (KAUNAS, LITHUANIA) 2025; 61:810. [PMID: 40428768 DOI: 10.3390/medicina61050810] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/09/2025] [Revised: 03/29/2025] [Accepted: 04/18/2025] [Indexed: 05/29/2025]
Abstract
Background and Objectives: Brain radionecrosis is an under-recognized but potentially life-altering late complication of radiotherapy in patients with locally advanced nasopharyngeal cancer. Temporal lobe radionecrosis and high-dose exposure to the hippocampus are strongly associated with cognitive decline and radiation-induced dementia, negatively impacting patients' long-term quality of life (QoL). This study aimed to evaluate and compare radiation dose distributions to critical brain structures across three radiotherapy techniques-3D conformal radiotherapy (3D-CRT), intensity-modulated radiotherapy (IMRT), and volumetric-modulated arc therapy (VMAT)-in order to assess potential neurocognitive risks and support hippocampal-sparing protocols. Materials and Methods: Ten patients previously treated with 3D-CRT were retrospectively replanned using IMRT and VMAT techniques on the Eclipse v13.3 (VARIAN) planning system. Bilateral hippocampi and temporal lobes were delineated as organs at risk (OARs) according to the RTOG atlas, and dosimetric parameters including D_max, D_mean, and D_min were recorded. V7.3 values were evaluated for hippocampal avoidance regions. Results: While IMRT and VMAT provided improved target volume coverage and reduced high-dose exposure to many standard OARs, both techniques were associated with increased D_mean and D_min to the hippocampus and temporal lobes compared to 3D-CRT. The highest D_max values to the temporal lobes were observed in 3D-CRT plans, indicating a potential risk of radionecrosis. VMAT plans showed hippocampal mean doses exceeding 10 Gy in some cases, with V7.3 > 40%, breaching established neurocognitive risk thresholds. Conclusions: These findings support the routine delineation of the hippocampus and temporal lobes as OARs in radiotherapy planning for nasopharyngeal cancer. The implementation of hippocampal-sparing strategies, particularly in IMRT and VMAT, is recommended to reduce the risk of radiation-induced cognitive toxicity and preserve long-term QoL in survivors.
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Affiliation(s)
| | | | | | - Roxana Irina Iancu
- Oral Pathology Department, Faculty of Dental Medicine, "Gr. T. Popa" University of Medicine and Pharmacy, 700115 Iaşi, Romania
- "St. Spiridon" Emergency Hospital, 700111 Iaşi, Romania
| | - Dragoș Petru Teodor Iancu
- Regional Institute of Oncology, 700483 Iaşi, Romania
- Oncology and Radiotherapy Department, Faculty of Medicine, "Gr. T. Popa" University of Medicine and Pharmacy, 700115 Iaşi, Romania
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Oh J, Patel S, Schlosser MP, Arifin AJ, Oliveira C, Charpentier AM, Tsang DS. Pediatric CNS Radiation Oncology: Recent Developments and Novel Techniques. Curr Oncol 2025; 32:180. [PMID: 40136384 PMCID: PMC11941344 DOI: 10.3390/curroncol32030180] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2025] [Revised: 03/11/2025] [Accepted: 03/12/2025] [Indexed: 03/27/2025] Open
Abstract
Radiation therapy (RT) is a cornerstone in the management of pediatric central nervous system (CNS) tumors. Recent advancements in RT delivery and techniques aim to enhance therapeutic effectiveness while minimizing both acute and long-term complications associated with pediatric brain RT. This paper highlights innovative developments in the field, including the clinical indications, benefits, and challenges of proton therapy and stereotactic radiotherapy. The ongoing refinement of risk-adapted RT volumes is highlighted, with examples of newly proposed germinoma RT volumes and hippocampal-sparing RT. Additionally, emerging experimental approaches, including FLASH therapy and theranostics, are also discussed as promising future directions. Further prospective, multi-institutional collaborative studies are essential to validate and expand upon the benefits outlined in this review.
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Affiliation(s)
- Justin Oh
- BC Cancer—Vancouver, Vancouver, BC V5Y 4E6, Canada
| | - Samir Patel
- Cross Cancer Institute, Edmonton, AB T6G 1Z2, Canada;
| | | | | | - Carol Oliveira
- McGill University Health Centre, Montreal, QC H4A 0B1, Canada;
| | | | - Derek S. Tsang
- Princess Margaret Cancer Centre, Toronto, ON M5G 2C4, Canada;
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Ziemann C, Cremers F, MacPherson M, Rades D, Löser A. A New Approach to Highly Conformal Hippocampal-sparing Whole-brain Radiotherapy: A Feasibility Study. In Vivo 2025; 39:834-843. [PMID: 40010946 PMCID: PMC11884443 DOI: 10.21873/invivo.13886] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2024] [Revised: 11/25/2024] [Accepted: 11/27/2024] [Indexed: 02/28/2025]
Abstract
BACKGROUND/AIM Hippocampal-sparing whole-brain radiotherapy (HS-WBRT) is increasingly used for multiple brain metastases. However, most studies have not reported dose conformity indices (CI). In the only study indicating the CI, conformity was low (CI=0.7). We developed a new technique to achieve a significantly higher CI and better dose coverage. PATIENTS AND METHODS Ten patients received 30 Gy of HS-WBRT for brain metastases. Three variants of treatment plans (VAR1, VAR2, VAR3) were investigated. Volumetric modulated arc therapy plans with two (2ROT) or three rotations (3ROT) were created for each variant. Plans were compared for compliance with hippocampal sparing criteria, CI (where a higher value indicates better conformity), and homogeneity index (HI, where a lower value indicates better homogeneity). RESULTS Best results (highest CI, lowest HI) were achieved with the VAR3-3ROT technique (a new method), which yielded a CI=0.92-0.95 and a HI=0.05-0.09. VAR3-2ROT led to a CI=0.90-0.95 and a HI=0.06-0.11. With the other techniques, CI and HI ranged between 0.77-0.87 and 0.15-0.32, respectively. CONCLUSION Our new technique achieved both appropriate hippocampal sparing and very high dose conformity of ≥0.9. Significant underdosage outside the hippocampal-sparing area was avoided.
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Affiliation(s)
- Christian Ziemann
- Department of Radiation Oncology, University of Lübeck, Lübeck, Germany;
| | - Florian Cremers
- Department of Radiation Oncology, University of Lübeck, Lübeck, Germany
| | - Miller MacPherson
- Division of Medical Physics, Department of Radiology, Faculty of Medicine, University of Ottawa, Ottawa, Canada
| | - Dirk Rades
- Department of Radiation Oncology, University of Lübeck, Lübeck, Germany
| | - Anastassia Löser
- Department of Radiation Oncology, University of Lübeck, Lübeck, Germany
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McCarthy S, Clark R, Magliari A, St. Clair W, Pokhrel D. Automated hippocampal sparing whole brain radiotherapy with simultaneous integrated boost for multiple brain metastases: Halcyon, HyperArc on TrueBeam, and coplanar TrueBeam. J Appl Clin Med Phys 2025; 26:e14570. [PMID: 39611851 PMCID: PMC11799903 DOI: 10.1002/acm2.14570] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2024] [Revised: 09/15/2024] [Accepted: 10/01/2024] [Indexed: 11/30/2024] Open
Abstract
PURPOSE To demonstrate the ease and feasibility that hippocampal sparing whole brain (WB) simultaneous integrated boost (HSWB-SIB) plans can be generated using knowledge-based planning and Eclipse Scripting Application Programming Interface (ESAPI) for three different modalities, HyperArc on TrueBeam (TB-HA), a coplanar beam arrangement on TrueBeam (TB-Co), and the ring-mounted Halcyon LINAC (Hal). METHODS Twelve patients with 2-14 brain metastases were retrospectively replanned for HSWB-SIB using a published HSWB RapidPlan model with modifications for the automated addition of SIB to metastases. Prescribed dose was 30 Gy to the WB planning target volume (PTV) and 50 Gy to the metastases in 10 fractions. Eclipse treatment planning system (v16.1) was used with a 6 MV-FFF beam and Acuros XB dose algorithm. RESULTS The methodology was successfully used for all modalities, generating plans in under 30 min. The plan doses were normalized to the WB PTV D95% receiving 30 Gy. Reporting values in the order of Hal, TB-Co, and TB-HA: The WB PTV received a V48 Gy of 4.58, 3.98, and 4.45 cc with statistically insignificant differences (p = 0.806). The boost PTVs received a D95% of 50.60, 50.43, and 51.13 Gy with statistically significant comparisons between TB-HA and the other two modalities (p = 0.005). The hippocampus maximum dose was 11.81, 11.51, and 11.13 Gy with no statistically significant comparisons (p = 0.105). All other oragns-at-risk (OAR) doses were clinically acceptable. The modalities were evaluated using a dosimetric scorecard, achieving average scores of 84.85%, 86.45%, and 87.39%. End-to-end testing ensured the deliverability of the HSWB-SIB plans for all modalities. CONCLUSION The novel modification of the preexisting HSWB RapidPlan model with the automated inclusion of SIB objectives allows for easy, intuitive planning of complex HSWB-SIB treatments. All modalities demonstrated can be used with clinically comparable results. Other institutions are recommended to pursue and validate this HSWB-SIB technique to increase the accessibility of a single-course of high-quality treatment for patients with multiple brain lesions.
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Affiliation(s)
- Shane McCarthy
- Department of Radiation MedicineUniversity of KentuckyLexingtonKentuckyUSA
| | - Ryan Clark
- Varian Medical SystemsPalo AltoCaliforniaUSA
| | | | - William St. Clair
- Department of Radiation MedicineUniversity of KentuckyLexingtonKentuckyUSA
| | - Damodar Pokhrel
- Department of Radiation MedicineUniversity of KentuckyLexingtonKentuckyUSA
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Zeng H, Zhong M, Chen Z, Tang S, Wen Z. A dosimetric comparison of non-coplanar volumetric modulated arc therapy and non-coplanar fixed field intensity modulated radiation therapy in hippocampus-avoidance whole-brain radiation therapy with a simultaneous integrated boost for brain metastases. Front Oncol 2025; 14:1428329. [PMID: 39917360 PMCID: PMC11799273 DOI: 10.3389/fonc.2024.1428329] [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: 05/06/2024] [Accepted: 12/23/2024] [Indexed: 02/09/2025] Open
Abstract
Objective The aim of this study was to investigate the dosimetric differences between non-coplanar volumetric modulated arc therapy (VMAT) and non-coplanar fixed-field intensity-modulated radiotherapy (IMRT) in hippocampus-avoidance whole-brain radiation therapy with a simultaneous integrated boost (HA-WBRT+SIB) for brain metastases using the Monaco treatment planning system (TPS). Method A total of 22 patients with brain metastases were retrospectively enrolled. Two radiotherapy treatment plans were designed for each patient: non-coplanar VMAT and non-coplanar fixed field IMRT. The dose distribution of targets and organs at risk (OAR), the number of monitor units (MUs), and pre-treatment plan verification were compared between the two plans while meeting the prescribed dose requirements of the target volume. Results There were no significant differences in V50, V55, Dmax, heterogeneity index (HI) and conformity index (CI) of target PGTV between the two plans (p>0.05). For PTV-brain-SIB, there was no significant difference in D98% between IMRT and VMAT (p=0.103). VMAT significantly improved the V30 of PTV-brain-SIB (p<0.001), decreased HI (p=0.003), and increased CI (p<0.001). There were no significant differences in the Dmax to the brain stem, left and right lens, optic chiasm, pituitary gland, and left and right hippocampus between the two plans (p>0.05). Compared with IMRT, VMAT significantly reduced the Dmax to the left and right eyes (p<0.001) and significantly increased the Dmax to the right inner ear (p=0.010). There was no significant difference in the Dmax to the left inner ear between VMAT and IMRT (p=0.458). Compared with IMRT, VMAT significantly reduced the Dmax to the left optic nerve (p=0.006), but significantly increased the Dmax to the right optic nerve (p=0.001). There was no significant difference in the Dmax to the left and right hippocampus between VMAT and IMRT (p>0.05), but VMAT significantly increased the D100% (p<0.05) compared with IMRT. Compared with VMAT, IMRT significantly reduced the MU (p<0.001) but VMAT has a higher treatment efficiency than IMRT, with an average reduction of 41 seconds (294.1 ± 16.4 s for VMAT, 335.8 ± 34.9 s for IMRT, p<0.001). Under the conditions of 3%/2 mm, and 2%/2 mm, the gamma passing rate of the IMRT QA was improved compared to VMAT, with an average increase of 0.6%, p=0.013, and 1.7%, p<0.001, respectively. Conclusion Both non-coplanar VMAT and non-coplanar fixed field IMRT based on the Monaco TPS produce clinically acceptable results for HA-WBRT+SIB in patients with brain metastases. Compared with IMRT, VMAT has better dose distribution in the target volume and treatment efficiency, but IMRT can better protect the hippocampus and reduce the number of MUs.
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Affiliation(s)
- Huaqu Zeng
- Radiotherapy Center, Gaozhou People’s Hospital, Gaozhou, China
| | - MinZhi Zhong
- Department of Radiology, Guangzhou Red Cross Hospital, Guangzhou, China
| | - Zongyou Chen
- Radiotherapy Center, Gaozhou People’s Hospital, Gaozhou, China
| | - Shukui Tang
- Radiotherapy Center, Gaozhou People’s Hospital, Gaozhou, China
| | - Zunbei Wen
- Radiotherapy Center, Gaozhou People’s Hospital, Gaozhou, China
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10
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Lens M, Schachter J. The Role of Radiotherapy in the Management of Melanoma Brain Metastases: An Overview. Curr Treat Options Oncol 2025; 26:36-44. [PMID: 39752093 PMCID: PMC11769869 DOI: 10.1007/s11864-024-01289-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/13/2024] [Indexed: 01/04/2025]
Abstract
OPINION STATEMENT Clinical management of melanoma brain metastases is complex and requires multidisciplinary approach. With close collaboration between neurosurgeons, radiation oncologists and medical oncologists, melanoma patients with brain are offered different treatment modalities: surgery, radiation therapy, systemic therapy or combined treatments. Radiation therapy (whole brain radiotherapy- WBRT and stereotactic radiosurgery- SRS) is an integral part of treating melanoma brain metastases. Use of immunotherapy (checkpoint inhibitors) and targeted therapy (BRAF/MEK inhibitors) significantly changed the outcome in patients with melanoma metastases. Currently, ipilimumab and nivolumab (COMBO) is the preferred first-line systemic therapy for all patients with asymptomatic brain metastases, regardless of BRAF status (BRAF wild-type and BRAF-mutated). Although at the moment there is no consensus on the concomitant use of SRS and COMBO, results from clinical trials suggest that this combined treatment modality should be considered the standard of care for melanoma patients with brain metastases. However, further clinical research is required to define optimal treatment modalities for routine management of melanoma brain lesions.
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Affiliation(s)
- Marko Lens
- University of Leeds, Beckett Street, Leeds, LS9 7TF, UK.
| | - Jacob Schachter
- Ella Lemelbaum Institute for Immuno Oncology, Chaim Sheba Medical Center, 6997801, Tel Aviv, Israel
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11
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Porter EM, Vu C, Sala IM, Guerrero T, Siddiqui ZA. Deep learning for contour quality assurance for RTOG 0933: In-silico evaluation. Radiother Oncol 2024; 201:110519. [PMID: 39222847 DOI: 10.1016/j.radonc.2024.110519] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2023] [Revised: 08/14/2024] [Accepted: 08/30/2024] [Indexed: 09/04/2024]
Abstract
PURPOSE To validate a CT-based deep learning (DL) hippocampal segmentation model trained on a single-institutional dataset and explore its utility for multi-institutional contour quality assurance (QA). METHODS A DL model was trained to contour hippocampi from a dataset generated by an institutional observer (IO) contouring on brain MRIs from a single-institution cohort. The model was then evaluated on the RTOG 0933 dataset by comparing the treating physician (TP) contours to blinded IO and DL contours using Dice and Haussdorf distance (HD) agreement metrics as well as evaluating differences in dose to hippocampi when TP vs. IO vs. DL contours are used for planning. The specificity and sensitivity of the DL model to capture planning discrepancies was quantified using criteria of HD > 7 mm and Dmax hippocampi > 17 Gy. RESULTS The DL model showed greater agreement with IO contours compared to TP contours (DL:IO L/R Dice 74%/73%, HD 4.86/4.74; DL:TP L/R Dice 62%/65%, HD 7.23/6.94, all p < 0.001). Thirty percent of contours and 53 % of dose plans failed QA. The DL model achieved an AUC L/R 0.80/0.79 on the contour QA task via Haussdorff comparison and AUC of 0.91 via Dmax comparison. The false negative rate was 17.2%/20.5% (contours) and 5.8% (dose). False negative cases tended to demonstrate a higher DL:IO Dice agreement (L/R p = 0.42/0.03) and better qualitative visual agreement compared with true positive cases. CONCLUSION Our study demonstrates the feasibility of using a single-institutional DL model to perform contour QA on a multi-institutional trial for the task of hippocampal segmentation.
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Affiliation(s)
- Evan M Porter
- Department of Medical Physics, Wayne State University, Detroit, MI, United States.
| | - Charles Vu
- Department of Radiation Oncology, Corewell Health-East, Royal Oak, MI, United States
| | - Ina M Sala
- Department of Medical Physics, Wayne State University, Detroit, MI, United States; Department of Radiation Oncology, Corewell Health-East, Royal Oak, MI, United States
| | - Thomas Guerrero
- Department of Radiation Oncology, Corewell Health-East, Royal Oak, MI, United States
| | - Zaid A Siddiqui
- Department of Radiation Oncology, Corewell Health-East, Royal Oak, MI, United States.
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12
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Knight JA, Mourad WF, Nebbache H, Kaushal A. Atypical Cerebral Carcinoids Treated with Hippocampal-Sparing Whole Brain Radiotherapy. Cureus 2024; 16:e74997. [PMID: 39749082 PMCID: PMC11695048 DOI: 10.7759/cureus.74997] [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: 10/10/2024] [Accepted: 12/02/2024] [Indexed: 01/04/2025] Open
Abstract
Central nervous system (CNS) metastases of atypical carcinoid tumors are exceptionally rare. Isolated studies suggest a survival benefit in patients who receive whole-brain radiotherapy (WBRT); however, it has been known to have detrimental effects on long-term memory and executive function. Here, we present a case of a patient initially diagnosed with stage IIB bronchopulmonary carcinoid who later developed hepatic and intracranial metastases despite receiving adjuvant systemic therapy over a two-year period. She underwent hippocampal-sparing WBRT (HS-WBRT), receiving 30 Gy in 10 fractions via daily image-guided photon therapy using two coplanar arcs. Subsequent clinical evaluations and magnetic resonance imaging (MRI) of the brain at 11 months post-treatment demonstrated a decrease in the size and number of brain metastases, with the patient reporting stable memory and cognition. This case demonstrates the efficacious delivery of palliative HS-WBRT in a patient with a rare presentation of brain-metastatic atypical carcinoid, conferring effective local control and preservation of cognition. Multi-therapy regimens that incorporate HS-WBRT may be considered for improved disease control and quality of life. Further investigation of systemic agents, and possible molecular targets that could confer greater efficacy against treatment-progressive atypical carcinoids, is also warranted.
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Affiliation(s)
- James A Knight
- Radiation Medicine, University of Kentucky, Lexington, USA
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13
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Ospina JP, Wen PY. Medical and neurologic management of brain tumor patients. Curr Opin Neurol 2024; 37:657-665. [PMID: 39221926 DOI: 10.1097/wco.0000000000001315] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/04/2024]
Abstract
PURPOSE OF REVIEW This article discusses commonly encountered medical and neurological complications in patients with brain tumors and highlights recommendations for their management based on updated evidence. RECENT FINDINGS Use of dexamethasone is correlated with worse prognosis in patients with glioblastoma, and in brain metastases, high doses may lead to increased side effects without additional clinical benefit. There are multiple antiseizure medications (ASM) to choose from and possible interactions and toxicity must be considered when choosing an agent. Additionally, there is growing interest in the use of AMPA receptor blockers as ASM in patients with brain tumors. Nonpharmacological strategies for the management of fatigue remain paramount. Cognitive decline is common after whole brain radiation (WBRT) and hippocampal-sparing WBRT results in superior cognitive outcomes. Venous thromboembolism is a common complication and there is growing evidence on the use of direct oral anticoagulants (DOACs) in this population. SUMMARY There is evolving evidence on the management of medical and neurological complications in patients with brain tumors. These complications, require early identification and multidisciplinary collaboration and expertise.
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Affiliation(s)
- Juan Pablo Ospina
- Center for Neuro-Oncology, Dana-Farber Cancer Institute
- Division of Neuro-Oncology, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School
- Department of Neurology, Pappas Center for Neuro-Oncology, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Patrick Y Wen
- Center for Neuro-Oncology, Dana-Farber Cancer Institute
- Division of Neuro-Oncology, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School
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14
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Zhan TY, Deng L, Wang WQ, Zhang T, Wang JY, Wang X, Liu WY, Zhai YR, Xiao ZF, Feng QF, Bi N, Li YX, Zhou ZM. Implementing the optimized hippo-avoidance prophylactic cranial irradiation for limited-stage small cell lung cancer by tomotherapy and volumetric modulated arc therapy. Thorac Cancer 2024. [PMID: 39440477 DOI: 10.1111/1759-7714.15462] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2024] [Revised: 09/13/2024] [Accepted: 09/24/2024] [Indexed: 10/25/2024] Open
Abstract
BACKGROUND Hippo-avoidance prophylactic cranial irradiation (HA-PCI) requires a hippocampal avoidance zone expanded from hippocampus to ensure dose fall-off and compensate for setup errors. Most studies recommend a 5-mm margin, while it could be optimized to a 2-mm expansion. Here, we showed the details of optimized HA-PCI for limited-stage small cell lung cancer (LS-SCLC). METHODS This cohort study reviewed patients with LS-SCLC receiving optimized HA-PCI from August 2014 to June 2020 in the National Cancer Center of China. The hippo-related dose parameters were summarized. The comparison of the Hopkins Verbal Learning Test-Revised (HVLT-R) scores in different time points was conducted. The Kaplan-Meier method was used to calculate the survival rates. RESULTS A total of 112 patients were included. The average doses of hippocampus and hippocampal avoidance zone were 6.80 Gy (IQR: 6.40-7.44) and 7.63 Gy (IQR: 7.14-8.39). No differences were observed in the two radiation techniques (tomotherapy [TOMO] vs. volumetric-modulated arc therapy [VMAT]). The decline of HVLT-R score remained in a low level and not significant in assessable patients (p = 0.095). With a median follow-up of 52 months (95% CI: 47.2-56.7), the 2-year overall survival and progression-free survival were 74.1% and 50.0%, respectively. Two intracranial recurrence lesions (2.3%) located <2 mm from the hippocampus. CONCLUSIONS Optimized HA-PCI could achieve similar dose limitation by TOMO and VMAT techniques with favorable efficacy and minor toxicity.
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Affiliation(s)
- Tian-You Zhan
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China
| | - Lei Deng
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China
| | - Wen-Qing Wang
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China
| | - Tao Zhang
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China
| | - Jian-Yang Wang
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China
| | - Xin Wang
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China
| | - Wen-Yang Liu
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China
| | - Yi-Rui Zhai
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China
| | - Ze-Fen Xiao
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China
| | - Qin-Fu Feng
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China
| | - Nan Bi
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China
| | - Ye-Xiong Li
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China
| | - Zong-Mei Zhou
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China
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15
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Li L, Lu Z, Jiang A, Sha G, Luo Z, Xie X, Ding X. Swin Transformer-based automatic delineation of the hippocampus by MRI in hippocampus-sparing whole-brain radiotherapy. Front Neurosci 2024; 18:1441791. [PMID: 39464425 PMCID: PMC11502472 DOI: 10.3389/fnins.2024.1441791] [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: 07/03/2024] [Accepted: 09/26/2024] [Indexed: 10/29/2024] Open
Abstract
Objective This study aims to develop and validate SwinHS, a deep learning-based automatic segmentation model designed for precise hippocampus delineation in patients receiving hippocampus-protected whole-brain radiotherapy. By streamlining this process, we seek to significantly improve workflow efficiency for clinicians. Methods A total of 100 three-dimensional T1-weighted MR images were collected, with 70 patients allocated for training and 30 for testing. Manual delineation of the hippocampus was performed according to RTOG0933 guidelines. The SwinHS model, which incorporates a 3D ELSA Transformer module and an sSE CNN decoder, was trained and tested on these datasets. To prove the effectiveness of SwinHS, this study compared the segmentation performance of SwinHS with that of V-Net, U-Net, ResNet and VIT. Evaluation metrics included the Dice similarity coefficient (DSC), Jaccard similarity coefficient (JSC), and Hausdorff distance (HD). Dosimetric evaluation compared radiotherapy plans generated using automatic segmentation (plan AD) versus manual hippocampus segmentation (plan MD). Results SwinHS outperformed four advanced deep learning-based models, achieving an average DSC of 0.894, a JSC of 0.817, and an HD of 3.430 mm. Dosimetric evaluation revealed that both plan (AD) and plan (MD) met treatment plan constraints for the target volume (PTV). However, the hippocampal Dmax in plan (AD) was significantly greater than that in plan (MD), approaching the 17 Gy constraint limit. Nonetheless, there were no significant differences in D100% or maximum doses to other critical structures between the two plans. Conclusion Compared with manual delineation, SwinHS demonstrated superior segmentation performance and a significantly shorter delineation time. While plan (AD) met clinical requirements, caution should be exercised regarding hippocampal Dmax. SwinHS offers a promising tool to enhance workflow efficiency and facilitate hippocampal protection in radiotherapy planning for patients with brain metastases.
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Affiliation(s)
- Liang Li
- Department of Radiotherapy, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
| | - Zhennan Lu
- Department of Equipment, Affiliated Hospital of Nanjing University of Chinese Medicine (Jiangsu Province Hospital of Chinese Medicine), Nanjing, China
| | - Aijun Jiang
- Department of Radiotherapy, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
| | - Guanchen Sha
- Department of Radiation Oncology, Xuzhou Central Hospital, Xuzhou, China
| | - Zhaoyang Luo
- HaiChuang Future Medical Technology Co., Ltd., Zhejiang, China
| | - Xin Xie
- Department of Radiotherapy, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
| | - Xin Ding
- Department of Radiotherapy, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
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16
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Martín-Tovar EA, Badillo-Alvarado AH, Cocom-Poot LE, Gaxiola-Sosa JL. Modulated Arc Therapy for hippocampal-avoidance whole brain radiation therapy: planning comparison with intensity modulated Radiation Therapy. RADIATION AND ENVIRONMENTAL BIOPHYSICS 2024; 63:443-454. [PMID: 38809486 DOI: 10.1007/s00411-024-01075-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/09/2023] [Accepted: 05/25/2024] [Indexed: 05/30/2024]
Abstract
This study aimed to evaluate the modulated arc therapy (mARC) technique as a planning and treatment option for hippocampal sparing whole brain radiotherapy (HS-WBRT) following the Radiation Therapy Oncology Group (RTOG) 0933 dosimetric criteria. Computed tomography (CT) and magnetic resonance imaging (MRI) were selected retrospectively for 15 patients. Two types of plans were created for each patient, namely an intensity-modulated radiation therapy (IMRT) and a mARC plan. IMRT and mARC plans were compared in terms of plan quality indices, absorbed dose to organs at risk (OARs), number of monitor units (MUs), and treatment time. All plans in both techniques were considered clinically acceptable for treatment. However, IMRT plans presented a higher conformity (p = 0.01) as well as a higher homogeneity as compared to mARC plans, but this difference was not statistically significant (p > 0.05). In terms of the preservation of the hippocampus, it was observed that the IMRT plans achieved significantly lower doses for both 100% of its volume and for its maximum dose (p < 0.001). The evaluation of the remaining OARs showed that the IMRT technique resulted in lower doses, and significant differences were observed for the following organs: left cochlea (p < 0.001), left eye (p < 0.001), right eye (p = 0.03), both lenses of the eye (p < 0.001), and right optic nerve (p = 0.02). Despite these differences, the absolute differences in all dosimetric parameters were low enough to bear any clinical relevance. A drastic (close to 65%) and significant (p < 0.001) decrease was observed in the number of MUs for the mARC plans. This resulted in a substantial decrease in treatment time (60.45%, p < 0.001). It is concluded that the mARC technique is a feasible planning and treatment solution for HS-WBRT that meets the RTOG 0933 criteria. The main advantage of using mARC over IMRT for HS-WBRT is the considerable reduction in MUs and treatment time.
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Affiliation(s)
- E A Martín-Tovar
- División de Oncología y Uronefrología, Departamento de Radioterapia, Unidad Médica de Alta Especialidad, Hospital de Especialidades del Centro Médico Nacional "Ignacio García Téllez", Instituto Mexicano del Seguro Social, Mérida Yucatán, CP 97150, México.
| | - A H Badillo-Alvarado
- División de Oncología y Uronefrología, Departamento de Radioterapia, Unidad Médica de Alta Especialidad, Hospital de Especialidades del Centro Médico Nacional "Ignacio García Téllez", Instituto Mexicano del Seguro Social, Mérida Yucatán, CP 97150, México
| | - L E Cocom-Poot
- División de Oncología y Uronefrología, Departamento de Radioterapia, Unidad Médica de Alta Especialidad, Hospital de Especialidades del Centro Médico Nacional "Ignacio García Téllez", Instituto Mexicano del Seguro Social, Mérida Yucatán, CP 97150, México
| | - J L Gaxiola-Sosa
- División de Oncología y Uronefrología, Departamento de Radioterapia, Unidad Médica de Alta Especialidad, Hospital de Especialidades del Centro Médico Nacional "Ignacio García Téllez", Instituto Mexicano del Seguro Social, Mérida Yucatán, CP 97150, México
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17
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Wiegreffe S, Sarria GR, Layer JP, Dejonckheere E, Nour Y, Schmeel FC, Anton Giordano F, Schmeel LC, Popp I, Grosu AL, Gkika E, Stefaan Dejonckheere C. Incidence of hippocampal and perihippocampal brain metastases and impact on hippocampal-avoiding radiotherapy: A systematic review and meta-analysis. Radiother Oncol 2024; 197:110331. [PMID: 38772476 DOI: 10.1016/j.radonc.2024.110331] [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: 03/28/2024] [Revised: 04/25/2024] [Accepted: 05/03/2024] [Indexed: 05/23/2024]
Abstract
BACKGROUND AND PURPOSE In patients requiring prophylactic cranial irradiation (PCI) or whole-brain radiotherapy (WBRT) for brain metastases (BMs), hippocampal avoidance (HA) has been shown to preserve neurocognitive function and quality of life. Here, we aim to estimate the incidence of hippocampal and perihippocampal BMs and the subsequent risk of local undertreatment in patients undergoing hippocampal sparing radiotherapy. MATERIALS AND METHODS MEDLINE, Embase, and Scopus were searched with the terms "Hippocampus", "Brain Neoplasms", and related terms. Trials reporting on the incidence of hippocampal and/or perihippocampal BMs or hippocampal failure rate after PCI or WBRT were included. RESULTS Forty records were included, encompassing a total of 5,374 patients with over 32,570 BMs. Most trials employed a 5 mm margin to define the HA zone. In trials reporting on BM incidence, 4.4 % (range 0 - 27 %) and 9.2 % (3 - 41 %) of patients had hippocampal and perihippocampal BMs, respectively. The most common risk factor for hippocampal BMs was the total number of BMs. The reported failure rate within the HA zone after HA-PCI or HA-WBRT was 4.5 % (0 - 13 %), salvageable with radiosurgery in most cases. SCLC histology was not associated with a higher risk of hippocampal failure (OR = 2.49; p = 0.23). In trials comparing with a conventional (non-HA) PCI or WBRT group, HA did not increase the hippocampal failure rate (OR = 1.90; p = 0.17). CONCLUSION The overall incidence of hippocampal and perihippocampal BMs is considerably low, with a subsequent low risk of local undertreatment following HA-PCI or HA-WBRT. In patients without involvement, the hippocampus should be spared to preserve neurocognitive function and quality of life.
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Affiliation(s)
- Shari Wiegreffe
- Department of Radiation Oncology, University Hospital Bonn, 53127 Bonn, Germany
| | | | - Julian Philipp Layer
- Department of Radiation Oncology, University Hospital Bonn, 53127 Bonn, Germany; Institute of Experimental Oncology, University Hospital Bonn, 53127 Bonn, Germany
| | - Egon Dejonckheere
- Faculty of Psychology and Educational Sciences, KU Leuven, 3000 Leuven, Belgium; Department of Medical and Clinical Psychology, Tilburg School of Social and Behavioural Sciences, 5037 Tilburg, the Netherlands
| | - Younèss Nour
- Department of Radiation Oncology, University Hospital Bonn, 53127 Bonn, Germany
| | | | - Frank Anton Giordano
- Department of Radiation Oncology, University Medical Center Mannheim, 68167 Mannheim, Germany; DKFZ-Hector Cancer Institute, University Medical Center Mannheim, 68167 Mannheim, Germany
| | | | - Ilinca Popp
- Department of Radiation Oncology, Medical Faculty, University Freiburg, 79106 Freiburg, Germany
| | - Anca-Ligia Grosu
- Department of Radiation Oncology, Medical Faculty, University Freiburg, 79106 Freiburg, Germany
| | - Eleni Gkika
- Department of Radiation Oncology, University Hospital Bonn, 53127 Bonn, Germany
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18
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Tang L, Tian G, Li N. Current dilemma and future directions over prophylactic cranial irradiation in SCLC: a systematic review in MRI and immunotherapy era. Front Oncol 2024; 14:1382220. [PMID: 39139283 PMCID: PMC11319250 DOI: 10.3389/fonc.2024.1382220] [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: 02/10/2024] [Accepted: 07/15/2024] [Indexed: 08/15/2024] Open
Abstract
Small cell lung cancer (SCLC) is the most malignant pathological type of lung cancer with the highest mortality, and the incidence of brain metastasis (BM) is in high frequency. So far, prophylactic cranial irradiation (PCI) has been suggested as an effective treatment for preventing brain metastasis of SCLC. PCI has long been applied to limited-stage SCLC (LS-SCLC) patients who have achieved complete remission after radiotherapy and chemotherapy as a standard treatment. However, the neurocognitive decline is a major concern surrounding PCI. New therapeutic approaches targeting PCI-induced neurotoxicity, including hippocampal protection or memantine, have been increasingly incorporated into the therapeutic interventions of PCI. Helical tomotherapy, RapidArc, and Volumetric-modulated arc therapy (VMAT) with a head-tilting baseplate are recommended for hippocampal protection. Besides, in the MRI and immunotherapy era, the significance of PCI in SCLC patients is controversial. SCLC patients with PCI should be recruited in clinical trials since this is the only way to improve the existing standard of care. This review summarizes the current therapeutic strategy and dilemma over PCI for SCLC, providing a theoretical basis for clinical decision-making and suggestions for PCI practice in clinical.
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Affiliation(s)
| | | | - Nan Li
- Department of Radiation Oncology, the First Hospital of China Medical University, Shenyang, China
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19
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Mahajan A, Stavinoha PL, Rongthong W, Brodin NP, McGovern SL, El Naqa I, Palmer JD, Vennarini S, Indelicato DJ, Aridgides P, Bowers DC, Kremer L, Ronckers C, Constine L, Avanzo M. Neurocognitive Effects and Necrosis in Childhood Cancer Survivors Treated With Radiation Therapy: A PENTEC Comprehensive Review. Int J Radiat Oncol Biol Phys 2024; 119:401-416. [PMID: 33810950 DOI: 10.1016/j.ijrobp.2020.11.073] [Citation(s) in RCA: 32] [Impact Index Per Article: 32.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2020] [Revised: 11/08/2020] [Accepted: 11/12/2020] [Indexed: 12/12/2022]
Abstract
PURPOSE A PENTEC review of childhood cancer survivors who received brain radiation therapy (RT) was performed to develop models that aid in developing dose constraints for RT-associated central nervous system (CNS) morbidities. METHODS AND MATERIALS A comprehensive literature search, through the PENTEC initiative, was performed to identify published data pertaining to 6 specific CNS toxicities in children treated with brain RT. Treatment and outcome data on survivors were extracted and used to generate normal tissue complication probability (NTCP) models. RESULTS The search identified investigations pertaining to 2 of the 6 predefined CNS outcomes: neurocognition and brain necrosis. For neurocognition, models for 2 post-RT outcomes were developed to (1) calculate the risk for a below-average intelligence quotient (IQ) (IQ <85) and (2) estimate the expected IQ value. The models suggest that there is a 5% risk of a subsequent IQ <85 when 10%, 20%, 50%, or 100% of the brain is irradiated to 35.7, 29.1, 22.2, or 18.1 Gy, respectively (all at 2 Gy/fraction and without methotrexate). Methotrexate (MTX) increased the risk for an IQ <85 similar to a generalized uniform brain dose of 5.9 Gy. The model for predicting expected IQ also includes the effect of dose, age, and MTX. Each of these factors has an independent, but probably cumulative effect on IQ. The necrosis model estimates a 5% risk of necrosis for children after 59.8 Gy or 63.6 Gy (2 Gy/fraction) to any part of the brain if delivered as primary RT or reirradiation, respectively. CONCLUSIONS This PENTEC comprehensive review establishes objective relationships between patient age, RT dose, RT volume, and MTX to subsequent risks of neurocognitive injury and necrosis. A lack of consistent RT data and outcome reporting in the published literature hindered investigation of the other predefined CNS morbidity endpoints.
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Affiliation(s)
- Anita Mahajan
- Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota.
| | - Peter L Stavinoha
- Division of Pediatrics, University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Warissara Rongthong
- Division of Radiation Oncology, Department of Radiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - N Patrik Brodin
- Department of Radiation Oncology, Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, New York
| | - Susan L McGovern
- Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Issam El Naqa
- Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan
| | - Joshua D Palmer
- Department of Radiation Oncology, James Cancer Hospital at Ohio State University, Nationwide Children's Hospital, Columbus, Ohio
| | - Sabina Vennarini
- Proton Therapy Center, Azienda Provinciale per I Servizi Sanitari, Trento, Italy
| | - Daniel J Indelicato
- Department of Radiation Oncology, University of Florida, Gainesville, Florida
| | - Paul Aridgides
- Department of Radiation Oncology, SUNY Upstate Medical University, Syracuse, New York
| | - Daniel C Bowers
- Division of Pediatric Hematology and Oncology, University of Texas Southwestern Medical School, Dallas, Texas
| | - Leontien Kremer
- Department of Pediatrics, UMC Amsterdam, Location AMC, Amsterdam, the Netherlands; Department of Pediatric Oncology, Princess Máxima Center for Paediatric Oncology, Utrecht, the Netherlands
| | - Cecile Ronckers
- Department of Pediatrics, UMC Amsterdam, Location AMC, Amsterdam, the Netherlands; Department of Pediatric Oncology, Princess Máxima Center for Paediatric Oncology, Utrecht, the Netherlands; Institute of Biostatistics and Registry Research, Medical University Brandenburg-Theodor Fontane, Neuruppin, Germany
| | - Louis Constine
- Department of Radiation Oncology, University of Rochester Medical Center, Rochester, New York
| | - Michele Avanzo
- Medical Physics Department, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy
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Han YM, Ou D, Chai WM, Yang WL, Liu YL, Xiao JF, Zhang W, Qi WX, Chen JY. Exploration of anatomical distribution of brain metastasis from breast cancer at first diagnosis assisted by artificial intelligence. Heliyon 2024; 10:e29350. [PMID: 38694110 PMCID: PMC11061689 DOI: 10.1016/j.heliyon.2024.e29350] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2023] [Revised: 04/03/2024] [Accepted: 04/05/2024] [Indexed: 05/03/2024] Open
Abstract
Objectives This study aimed to explore the spatial distribution of brain metastases (BMs) from breast cancer (BC) and to identify the high-risk sub-structures in BMs that are involved at first diagnosis. Methods Magnetic resonance imaging (MRI) scans were retrospectively reviewed at our centre. The brain was divided into eight regions according to its anatomy and function, and the volume of each region was calculated. The identification and volume calculation of metastatic brain lesions were accomplished using an automatically segmented 3D BUC-Net model. The observed and expected rates of BMs were compared using 2-tailed proportional hypothesis testing. Results A total of 250 patients with BC who presented with 1694 BMs were retrospectively identified. The overall observed incidences of the substructures were as follows: cerebellum, 42.1 %; frontal lobe, 20.1 %; occipital lobe, 9.7 %; temporal lobe, 8.0 %; parietal lobe, 13.1 %; thalamus, 4.7 %; brainstem, 0.9 %; and hippocampus, 1.3 %. Compared with the expected rate based on the volume of different brain regions, the cerebellum, occipital lobe, and thalamus were identified as higher risk regions for BMs (P value ≤ 5.6*10-3). Sub-group analysis according to the type of BC indicated that patients with triple-negative BC had a high risk of involvement of the hippocampus and brainstem. Conclusions Among patients with BC, the cerebellum, occipital lobe and thalamus were identified as higher-risk regions than expected for BMs. The brainstem and hippocampus were high-risk areas of the BMs in triple negative breast cancer. However, further validation of this conclusion requires a larger sample size.
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Affiliation(s)
- Yi-min Han
- Department of Radiation Oncology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Dan Ou
- Department of Radiation Oncology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Wei-min Chai
- Department of Radiology, RuiJin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Wen-lei Yang
- Department of Neurosurgery, RuiJin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Ying-long Liu
- United Imaging Research Institute of Innovative Medical Equipment, Shenzhen, China
| | - Ji-feng Xiao
- United Imaging Research Institute of Innovative Medical Equipment, Shenzhen, China
| | - Wei Zhang
- Shanghai United Imaging Healthcare Co., Ltd. Shanghai, China
| | - Wei-xiang Qi
- Department of Radiation Oncology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Jia-yi Chen
- Department of Radiation Oncology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
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21
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Crooks J, Dominic O, Shepard M, Yu A, Liang Y, Karlovits SM, Wegner RE. Cost of Treatment for Brain Metastases Using Data From a National Health Insurance. Adv Radiat Oncol 2024; 9:101438. [PMID: 38567144 PMCID: PMC10985802 DOI: 10.1016/j.adro.2024.101438] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2023] [Accepted: 12/29/2023] [Indexed: 04/04/2024] Open
Abstract
Purpose In the United States, brain metastases (BMs) affect 10% to 20% of patients with cancer, presenting a significant health care challenge and necessitating intricate, high-cost treatments. Few studies have explored the comprehensive care cost for BMs, and none have used real insurance claims data. Partnering with a northeastern health care insurer, we investigated the true costs of various brain-directed radiation methods, aiming to shed light on treatment expenses, modalities, and their efficacy. Methods and Materials We analyzed medical claims from Highmark Health-insured patients in Pennsylvania, Delware, West Virginia, and New York diagnosed with BMs (ICD-10 code C79.31) and treated with radiation from January 1, 2020 to July 1, 2022. Costs for radiation techniques were grouped by specific current procedural terminology claim codes. We subdivided costs into technical and physician components and separated hospital from freestanding costs for some modalities. Results From January 1, 2020 to July 1, 2022, 1048 Highmark Health members underwent treatment for BMs. Females (n = 592) significantly outnumbered males (n = 456), with an average age of 64.4 years. Each member had, on average, 5.309 claims costing $2015 per claim. Total cost totaled $10,697,749. Per-treatment analysis showed that hippocampal avoidance intensity modulated radiation therapy was the costliest treatment at $47,748, followed by stereotactic radiation therapy at $37,230, linear accelerator stereotactic radiosurgery (SRS) at $30,737, Gamma Knife SRS at $30,711, and whole-brain radiation therapy at $5225. Conclusions Whole-brain radiation therapy was the least costly radiation technique. Similar per-treatment prices for Gamma Knife and linear accelerator SRS support their use in treating BMs. Stereotactic radiation therapy in general was costlier on a per-use basis than SRS, prompting further scrutiny on its frequent use. Hippocampal avoidance intensity modulated radiation therapy was the costliest radiation therapy on a per-use basis by a moderate amount, prompting further discussion about its comparative cost effectiveness against other radiation modalities. This study underscores the importance of multiple considerations in treating BMs, such as tumor control, survival, side effects, and costs.
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Affiliation(s)
- Joseph Crooks
- Department of Medicine, Drexel University College of Medicine, Philadelphia, Pennsylvania
| | - Oralia Dominic
- Medical Policy Research Department, Highmark Health, Pittsburgh, Pennsylvania
| | - Matthew Shepard
- Department of Neurosurgery, Allegheny Health Network, Pittsburgh, Pennsylvania
| | - Alexander Yu
- Department of Neurosurgery, Allegheny Health Network, Pittsburgh, Pennsylvania
| | - Yun Liang
- Department of Radiation Oncology, Allegheny Health Network, Pittsburgh, Pennsylvania
| | - Stephen M. Karlovits
- Department of Radiation Oncology, Allegheny Health Network, Pittsburgh, Pennsylvania
| | - Rodney E. Wegner
- Department of Radiation Oncology, Allegheny Health Network, Pittsburgh, Pennsylvania
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22
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Balasubramanian S, Shobana MK, Anabalagan D, Thanasekar P, Joel S, Chaudhary P. Dosimetric and radiobiological comparison of IMRT, VMAT, and helical tomotherapy planning techniques in hippocampal sparing whole brain radiotherapy with simultaneous integrated boost for multiple brain metastases. RADIATION AND ENVIRONMENTAL BIOPHYSICS 2024; 63:47-57. [PMID: 38194100 DOI: 10.1007/s00411-023-01052-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/11/2023] [Accepted: 11/19/2023] [Indexed: 01/10/2024]
Abstract
To compare treatment planning and dosimetric outcomes for hippocampal sparing whole brain radiotherapy (WBRT) with the simultaneous integrated boost (SIB) in brain metastasis (BM) patients using tumour control probability (TCP) and normal tissue complication probability (NTCP) formalism between IMRT, VMAT, and HT techniques. In this retrospective study, the treatment data of 20 BM patients who typically received whole brain radiation with SIB treatment were used. Prescription doses of 30 Gy and 36 Gy was delivered in 10 fractions for WBRT and SIB, respectively. Niemierko and LKB models were applied for calculating TCP and NTCP. All the plans were evaluated for the RTOG 0933 protocol criteria and found acceptable. Additionally, the homogeneity of the PTV boost is 0.07 ± 0.01, 0.1 ± 0.04, and 0.08 ± 0.02 for IMRT, VMAT, and HT, respectively (P < 0.05). The percentage of TCP for the PTV boost was 99.99 ± 0.003, 99.98 ± 0.004, and 99.99 ± 0.002 of IMRT, VMAT, and HT, respectively, (P < 0.005). The NTCP value of the lenses was higher with the VMAT plan as compared to IMRT and HT Plans. The hippocampal NTCP values are equal in all three planning proficiencies. The techniques like IMRT, VMAT, and HT can reduce the dose received by hippocampus to the dosimetric threshold during the delivery of WBRT with hippocampal sparing and can simultaneously boost multiple metastases. Overall, the high-quality dose distribution, TCP, and NTCP comparison between all three planning techniques show that the HT technique has better results when compared to the VMAT and IMRT techniques.
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Affiliation(s)
- S Balasubramanian
- School of Advanced Sciences, Vellore Institute of Technology, Vellore, 632014, India
- Department of Radiation Oncology, Max Super Specialty Hospital, Ghaziabad, 201010, India
| | - M K Shobana
- School of Advanced Sciences, Vellore Institute of Technology, Vellore, 632014, India.
| | - D Anabalagan
- Department of Radiation Oncology, Max Super Specialty Hospital, Ghaziabad, 201010, India
| | - P Thanasekar
- Department of Radiation Oncology, Max Super Specialty Hospital, Ghaziabad, 201010, India
| | - S Joel
- Department of Radiation Oncology, Max Super Specialty Hospital, Ghaziabad, 201010, India
| | - Prekshi Chaudhary
- Department of Radiation Oncology, Max Super Specialty Hospital, Ghaziabad, 201010, India
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23
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Corrao G, Bergamaschi L, Eleonora Pierini V, Gaeta A, Volpe S, Pepa M, Zaffaroni M, Vincini MG, Fodor CI, Piperno G, Emiro F, Ferrari A, Gandini S, Cattani F, Orecchia R, Marvaso G, Jereczek-Fossa BA. Hippocampal region avoidance in whole brain radiotherapy in brain metastases: For all or for some? A real-world feasibility report. TUMORI JOURNAL 2024; 110:34-43. [PMID: 38182553 DOI: 10.1177/03008916231206926] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2024]
Abstract
PURPOSE Hippocampal sparing whole-brain radiotherapy (HS-WBRT) showed significantly lower long-term side effects compared to standard WBRT. Aim of this study is to describe a HS-WBRT real-world monoinstitutional experience within a retrospective cohort. METHODS Patients who completed HS-WBRT course, with Karnofsky Performance Status ⩾ 60 and radiological diagnosis of brain metastases (BMs) were enrolled. Treatment was performed using helical Tomotherapy scheduled in 30 Gy in 10 or 12 fractions or 25 Gy in 10 fractions. Oncological outcomes were clinically and radiologically assessed every three months. Toxicity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events 4.3. RESULTS One hundred and nineteen patients from 2016 to 2020 met inclusion criteria; after a median follow-up of 18 months, 29 patients were alive; 6- and 12-months overall survival rates were 66% and 41%, respectively. HS-WBRT response was assessed for 72 patients. Median time to any progression and intracranial failure (IF) was 4.5 and 13.7 months, respectively. The 6- and 12-month IF rates were 85% and 57%. Among 40 patients (34%) who experienced IF, 17 (42%) were oligometastatic, 23 (58%) polymetastatic and 15/40 developed IF within the hippocampi avoidance zone. No grade (G) ⩾ 2 acute toxicities were reported and one G2 (dizziness) late toxicity was described. CONCLUSIONS HS-WBRT is well tolerated, and despite the hippocampal sparing region, the oncological control is satisfying. Further investigation is warranted to find patients who could most benefit from a HS-WBRT approach.
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Affiliation(s)
- Giulia Corrao
- Division of Radiation Oncology, IEO, European Institute of Oncology IRCCS, Milan, Italy
| | - Luca Bergamaschi
- Division of Radiation Oncology, IEO, European Institute of Oncology IRCCS, Milan, Italy
| | - Vanessa Eleonora Pierini
- Division of Radiation Oncology, IEO, European Institute of Oncology IRCCS, Milan, Italy
- Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy
| | - Aurora Gaeta
- Molecular and Pharmaco-Epidemiology Unit, Department of Experimental Oncology, IEO, European Institute of Oncology IRCCS, Milan, Italy
| | - Stefania Volpe
- Division of Radiation Oncology, IEO, European Institute of Oncology IRCCS, Milan, Italy
- Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy
| | - Matteo Pepa
- Division of Radiation Oncology, IEO, European Institute of Oncology IRCCS, Milan, Italy
| | - Mattia Zaffaroni
- Division of Radiation Oncology, IEO, European Institute of Oncology IRCCS, Milan, Italy
| | - Maria Giulia Vincini
- Division of Radiation Oncology, IEO, European Institute of Oncology IRCCS, Milan, Italy
| | | | - Gaia Piperno
- Division of Radiation Oncology, IEO, European Institute of Oncology IRCCS, Milan, Italy
| | - Francesca Emiro
- Unit of Medical Physics, IEO, European Institute of Oncology IRCCS, Milan, Italy
| | - Annamaria Ferrari
- Division of Radiation Oncology, IEO, European Institute of Oncology IRCCS, Milan, Italy
| | - Sara Gandini
- Molecular and Pharmaco-Epidemiology Unit, Department of Experimental Oncology, IEO, European Institute of Oncology IRCCS, Milan, Italy
| | - Federica Cattani
- Unit of Medical Physics, IEO, European Institute of Oncology IRCCS, Milan, Italy
| | - Roberto Orecchia
- Scientific Direction, IEO, European Institute of Oncology IRCCS, Milan, Italy
| | - Giulia Marvaso
- Division of Radiation Oncology, IEO, European Institute of Oncology IRCCS, Milan, Italy
| | - Barbara Alicja Jereczek-Fossa
- Division of Radiation Oncology, IEO, European Institute of Oncology IRCCS, Milan, Italy
- Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy
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24
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Perlow HK, Nalin AP, Ritter AR, Addington M, Ward A, Liu M, Nappi C, Blakaj DM, Beyer SJ, Thomas EM, Grecula JC, Raval RR, Kotecha R, Boulter D, Dawson EL, Zoller W, Palmer JD. Advancing Beyond the Hippocampus to Preserve Cognition for Patients With Brain Metastases: Dosimetric Results From a Phase 2 Trial of Memory-Avoidance Whole Brain Radiation Therapy. Adv Radiat Oncol 2024; 9:101337. [PMID: 38405310 PMCID: PMC10885551 DOI: 10.1016/j.adro.2023.101337] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2023] [Accepted: 07/18/2023] [Indexed: 02/27/2024] Open
Abstract
Purpose Recent advances to preserve neurocognitive function in patients treated for brain metastases include stereotactic radiosurgery, hippocampal avoidance whole brain radiation therapy (WBRT), and memantine administration. The hippocampus, corpus callosum, fornix, and amygdala are key neurocognitive substructures with a low propensity for brain metastases. Herein, we report our preliminary experience using a "memory-avoidance" WBRT (MA-WBRT) approach that spares these substructures for patients with >15 brain metastases. Methods and Materials Ten consecutive patients treated with MA-WBRT on a phase 2 clinical trial were reviewed. In each patient, the hippocampi, amygdalae, corpus callosum, and fornix were contoured. Patients were not eligible for MA-WBRT if they had metastases in these substructures. A memory-avoidance region was created using a 5-mm volumetric expansion around these substructures. Hotspots were avoided in the hypothalamus and pituitary gland. Coverage of brain metastases was prioritized over memory avoidance dose constraints. Dose constraints for these avoidance structures included a D100% ≤ 9 Gy and D0.03 cm3 ≤ 16 Gy (variation acceptable to 20 Gy). LINAC-based volumetric modulated arc therapy plans were generated for a prescription dose of 30 Gy in 10 fractions. Results On average, the memory avoidance structure volume was 37.1 cm3 (range, 25.2-44.6 cm3), occupying 2.5% of the entire whole brain target volume. All treatment plans met the D100% dose constraint, and 8 of 10 plans met the D0.03 cm3 constraint, with priority given to tumor coverage for the remaining 2 cases. Target coverage (D98% > 25 Gy) and homogeneity (D2% ≤ 37.5 Gy) were achieved for all plans. Conclusions Modern volumetric modulated arc therapy techniques allow for sparing of the hippocampus, amygdala, corpus callosum, and fornix with good target coverage and homogeneity. After enrollment is completed, quality of life and cognitive data will be evaluated to assess the efficacy of MA-WBRT to mitigate declines in quality of life and cognition after whole brain radiation.
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Affiliation(s)
- Haley K. Perlow
- Department of Radiation Oncology, The Ohio State University Wexner Medical Center, Columbus, Ohio
| | - Ansel P. Nalin
- College of Medicine, The Ohio State University, Columbus, Ohio
| | - Alex R. Ritter
- Department of Radiation Oncology, The Ohio State University Wexner Medical Center, Columbus, Ohio
| | - Mark Addington
- Department of Radiation Oncology, The Ohio State University Wexner Medical Center, Columbus, Ohio
| | - Aubrie Ward
- Department of Radiation Oncology, The Ohio State University Wexner Medical Center, Columbus, Ohio
| | - Michal Liu
- Department of Radiation Oncology, The Ohio State University Wexner Medical Center, Columbus, Ohio
| | - Collin Nappi
- Department of Radiation Oncology, The Ohio State University Wexner Medical Center, Columbus, Ohio
| | - Dukagjin M. Blakaj
- Department of Radiation Oncology, The Ohio State University Wexner Medical Center, Columbus, Ohio
| | - Sasha J. Beyer
- Department of Radiation Oncology, The Ohio State University Wexner Medical Center, Columbus, Ohio
| | - Evan M. Thomas
- Department of Radiation Oncology, The Ohio State University Wexner Medical Center, Columbus, Ohio
| | - John C. Grecula
- Department of Radiation Oncology, The Ohio State University Wexner Medical Center, Columbus, Ohio
| | - Raju R. Raval
- Department of Radiation Oncology, The Ohio State University Wexner Medical Center, Columbus, Ohio
| | - Rupesh Kotecha
- Department of Radiation Oncology, Miami Cancer Institute, Baptist Health South Florida, Miami, Florida
| | - Daniel Boulter
- Department of Radiology, The Ohio State University Wexner Medical Center, Columbus, Ohio
| | - Erica L. Dawson
- Department of Neurology, The Ohio State University Wexner Medical Center, Columbus, Ohio
| | - Wesley Zoller
- Department of Radiation Oncology, The Ohio State University Wexner Medical Center, Columbus, Ohio
| | - Joshua D. Palmer
- Department of Radiation Oncology, The Ohio State University Wexner Medical Center, Columbus, Ohio
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25
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Laskowski M, Błaszczyk B, Setlak M, Kuca M, Lech A, Kłos K, Rudnik A. Assessment of Radiation Dosage to the Hippocampi during Treatment of Multiple Brain Metastases Using Gamma Knife Therapy. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:246. [PMID: 38399534 PMCID: PMC10889917 DOI: 10.3390/medicina60020246] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/21/2023] [Revised: 01/15/2024] [Accepted: 01/28/2024] [Indexed: 02/25/2024]
Abstract
Background and Objectives: Brain metastases (BMs) pose significant clinical challenges in systemic cancer patients. They often cause symptoms related to brain compression and are typically managed with multimodal therapies, such as surgery, chemotherapy, whole brain radiotherapy (WBRT), and stereotactic radiosurgery (SRS). With modern oncology treatments prolonging survival, concerns about the neurocognitive side effects of BM treatments are growing. WBRT, though widely used for multiple BMs, has recognized neurocognitive toxicity. SRS, particularly Gamma Knife (GK) therapy, offers a minimally invasive alternative with fewer side effects, suitable for patients with a quantifiable number of metastases and better prognoses. Materials and Methods: A retrospective analysis was conducted on 94 patients with multiple BMs treated exclusively with GK at an academic medical center. Patients with prior WBRT were excluded. This study focused on the mean radiation dose received by the hippocampal area, estimated according to the 'Hippocampal Contouring: A Contouring Atlas for RTOG 0933' guidelines. Results: The precision of GK equipment results in mean doses of radiation that are lower than those suggested by RTOG 0933 and observed in other studies. This precision may help mitigate cognitive dysfunction and other side effects of hippocampal irradiation. Conclusions: GK therapy facilitates the administration of smaller, safer radiation doses to the hippocampi, which is advantageous even for lesions in the temporal lobe. It is feasible to treat multiple metastases, including cases with more than 10, but it is typically reserved for patients with fewer metastases, with an average of 3 in this study. This underlines GK's potential for reducing adverse effects while managing BMs effectively.
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Affiliation(s)
- Maciej Laskowski
- Student Scientific Society, Department of Neurosurgery, Faculty of Medical Sciences in Katowice, Medical University of Silesia, 40-055 Katowice, Poland
| | - Bartłomiej Błaszczyk
- Department of Neurosurgery, University Clinical Center, Faculty of Medical Sciences in Katowice, Medical University of Silesia, 40-752 Katowice, Poland
- Exira Gamma Knife, 40-952 Katowice, Poland
| | - Marcin Setlak
- Department of Neurosurgery, University Clinical Center, Faculty of Medical Sciences in Katowice, Medical University of Silesia, 40-752 Katowice, Poland
| | - Maciej Kuca
- Student Scientific Society, Department of Neurosurgery, Faculty of Medical Sciences in Katowice, Medical University of Silesia, 40-055 Katowice, Poland
| | | | - Kamil Kłos
- Student Scientific Society, Department of Neurosurgery, Faculty of Medical Sciences in Katowice, Medical University of Silesia, 40-055 Katowice, Poland
| | - Adam Rudnik
- Department of Neurosurgery, University Clinical Center, Faculty of Medical Sciences in Katowice, Medical University of Silesia, 40-752 Katowice, Poland
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Williamson A, Houston P, Paterson J, Chalmers AJ, McLoone P, Fullerton N, Foo SY, James A, Nowicki S. Dosimetric comparison of hippocampal-sparing technologies in patients with low-grade glioma. Neurooncol Adv 2024; 6:vdae131. [PMID: 39220244 PMCID: PMC11364934 DOI: 10.1093/noajnl/vdae131] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/04/2024] Open
Abstract
Background Radiotherapy (RT) plays an integral role in the management of low-grade gliomas (LGG). Late toxicity from RT can cause progressive neurocognitive dysfunction. Radiation-induced damage to the hippocampus (HCP) plays a considerable role in memory decline. Advancements in photon planning software have resulted in the development of multi-criteria optimization (MCO) and HyperArc technologies which may improve HCP sparing while maintaining planning target volume (PTV) target coverage. Methods Three planning methods for hippocampal sparing (HS) were compared, volumetric modulated arc therapy (VMAT) without HS (VMAT_noHS), VMAT with HS (VMAT_HS), MCO with HS (MCO_HS), and HyperArc with HS (HyperArc_HS). Results Twenty-five patients were identified. The contralateral HCP was spared in 16 patients and bilateral HCP in 9 patients with superiorly located tumors. All 3 HS planning techniques showed significant reductions in dose to the spared HCP in contralateral cases but only VMAT_HS and MCO_HS achieved this in bilateral cases (P < .008). Only MCO_HS was superior to VMAT_HS in lowering the dose to both contralateral HCP and bilateral HCP in all measured metrics (P < .008). PTV and OAR (organ at risk) dose constraints were achieved for all plans. Conclusions This retrospective dosimetric study demonstrated the feasibility of HS for low-grade glioma. All 3 HS planning techniques achieved significant dose reductions to the spared contralateral hippocampus, but only MCO_HS and VMAT_HS achieved this in bilateral cases. MCO was superior to other planning techniques for sparing both bilateral and contralateral hippocampi.
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Affiliation(s)
- Aoife Williamson
- Department of Clinical Oncology, Beatson West of Scotland Cancer Centre, Glasgow, UK
| | - Peter Houston
- Department of Clinical Oncology, Beatson West of Scotland Cancer Centre, Glasgow, UK
| | - Jennifer Paterson
- Department of Clinical Oncology, Beatson West of Scotland Cancer Centre, Glasgow, UK
| | | | - Philip McLoone
- School of Health & Wellbeing, University of Glasgow, Glasgow, UK
| | - Natasha Fullerton
- Department of Neuroradiology, Institute of Neurosciences, QEUH, Glasgow, UK
| | - Sin Yee Foo
- Department of Neuroradiology, Institute of Neurosciences, QEUH, Glasgow, UK
| | - Allan James
- Department of Clinical Oncology, Beatson West of Scotland Cancer Centre, Glasgow, UK
| | - Stefan Nowicki
- Department of Clinical Oncology, Beatson West of Scotland Cancer Centre, Glasgow, UK
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Shah K, Bhartia V, Biswas C, Sahu A, Shetty PM, Singh V, Velayutham P, Awate SP, Moiyadi AV. Tumor location and neurocognitive function-Unravelling the association and identifying relevant anatomical substrates in intra-axial brain tumors. Neurooncol Adv 2024; 6:vdae020. [PMID: 38464948 PMCID: PMC10924535 DOI: 10.1093/noajnl/vdae020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/12/2024] Open
Abstract
Background Neurocognitive function is a key outcome indicator of therapy in brain tumors. Understanding the underlying anatomical substrates involved in domain function and the pathophysiological basis of dysfunction can help ameliorate the effects of therapy and tailor directed rehabilitative strategies. Methods Hundred adult diffuse gliomas were co-registered onto a common demographic-specific brain template to create tumor localization maps. Voxel-based lesion symptom (VLSM) technique was used to assign an association between individual voxels and neuropsychological dysfunction in various domains (attention and executive function (A & EF), language, memory, visuospatial/constructive abilities, and visuomotor speed). The probability maps thus generated were further co-registered to cortical and subcortical atlases. A permutation-based statistical testing method was used to evaluate the statistically and clinically significant anatomical parcels associated with domain dysfunction and to create heat maps. Results Neurocognition was affected in a high proportion of subjects (93%), with A & EF and memory being the most affected domains. Left-sided networks were implicated in patients with A & EF, memory, and language deficits with the perisylvian white matter tracts being the most common across domains. Visuospatial dysfunction was associated with lesions involving the right perisylvian cortical regions, whereas deficits in visuomotor speed were associated with lesions involving primary visual and motor output pathways. Conclusions Significant baseline neurocognitive deficits are prevalent in gliomas. These are multidomain and the perisylvian network especially on the left side seems to be very important, being implicated in dysfunction of many domains.
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Affiliation(s)
- Kanchi Shah
- Neurosurgical Services, Department of Surgical Oncology, Tata Memorial Center, Mumbai, Maharashtra, India
- Department of Health Sciences, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Vinayak Bhartia
- Computer Science and Engineering Department, Indian Institute of Technology (IIT) Bombay. Mumbai, Maharashtra, India
| | - Chandrima Biswas
- Neurosurgical Services, Department of Surgical Oncology, Tata Memorial Center, Mumbai, Maharashtra, India
- Department of Health Sciences, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Arpita Sahu
- Department of Health Sciences, Homi Bhabha National Institute, Mumbai, Maharashtra, India
- Department of Radiodiagnosis, Tata Memorial Center, Mumbai, Maharashtra, India
| | - Prakash M Shetty
- Neurosurgical Services, Department of Surgical Oncology, Tata Memorial Center, Mumbai, Maharashtra, India
- Department of Health Sciences, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Vikas Singh
- Neurosurgical Services, Department of Surgical Oncology, Tata Memorial Center, Mumbai, Maharashtra, India
- Department of Health Sciences, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Parthiban Velayutham
- Neurosurgical Services, Department of Surgical Oncology, Tata Memorial Center, Mumbai, Maharashtra, India
- Department of Health Sciences, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Suyash P Awate
- Computer Science and Engineering Department, Indian Institute of Technology (IIT) Bombay. Mumbai, Maharashtra, India
| | - Aliasgar V Moiyadi
- Neurosurgical Services, Department of Surgical Oncology, Tata Memorial Center, Mumbai, Maharashtra, India
- Department of Health Sciences, Homi Bhabha National Institute, Mumbai, Maharashtra, India
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Li Y, Yuan C, Chen D, Xu S, Jiang W, Huang J, Ye S, Zhang Y, Liang J, Liu C. Comparison of Different Head Tilt Angles in Tomotherapy and Volumetric Modulated Arc Therapy for Hippocampal-Avoidance Whole-Brain Radiotherapy. Technol Cancer Res Treat 2024; 23:15330338241281326. [PMID: 39233627 PMCID: PMC11375751 DOI: 10.1177/15330338241281326] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/06/2024] Open
Abstract
PURPOSE Hippocampal-avoidance whole-brain radiotherapy (HA-WBRT) planning can present challenges. This study examines the influence of head tilt angles on the dosimetric characteristics of target and organs at risk (OARs), aiming to identify the optimal tilt angle that yields optimal dosimetric outcomes using tomotherapy (TOMO). METHODS Eight patients diagnosed with brain metastases underwent CT scans at five tilt angles: [0°, 10°), [10°, 20°), [20°, 30°), [30°, 40°), and [40°, 45°]. Treatment plans were generated using TOMO and volumetric modulated arc therapy (VMAT). Dosimetric parameters including conformity index (CI), homogeneity index (HI), D2cc, D98%, and Dmean of PTV, as well as Dmax, and Dmean of OARs were analyzed. Furthermore, a comparison was made between the dosimetric parameters of TOMO and VMAT plans. Finally, delivery efficiency of TOMO plans were assessed. RESULTS For the PTV, [40°, 45°] tilt angle demonstrated significantly better conformity, homogeneity, lower D2cc, and lower Dmean for the PTV. Regarding the OARs, the [40°, 45°] head tilt angle demonstrated significantly lower Dmax and Dmean in hippocampus, eyes, optic chiasm, and optic nerves. The [40°, 45°] tilt angle also showed significantly lower Dmax for brainstem and cochleas, as well as a lower Dmean for lens. In the [40°,45°] tilt angle for HA-WBRT, TOMO showed superior performance over VMAT for the PTV. TOMO achieved lower Dmax for brainstem, cochleas, optic nerves, and optic chiasm, as well as a lower Dmean for hippocampus. Furthermore, a significant correlation was found between delivery time and the PTV projection length in the sagittal plane. CONCLUSION The TOMO plan utilizing a tilt angle range of [40°, 45°] demonstrated superior PTV conformity and uniformity, along with enhanced OARs sparing. Furthermore, it exhibited a dosimetric advantage over VMAT for PTV and most OARs at the same angle range.
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Affiliation(s)
- Yang Li
- National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, China
| | - Cuiyun Yuan
- National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, China
| | - Dongjie Chen
- National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, China
| | - Sisi Xu
- National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, China
| | - Wei Jiang
- National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, China
| | - Jiaxin Huang
- National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, China
| | - Shanshan Ye
- National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, China
| | - Yin Zhang
- National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, China
| | - Jun Liang
- National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, China
| | - Chenbin Liu
- National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, China
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Zhang H, Hu B, Pang H. Dosimetric comparison of helical tomotherapy and volumetric modulated arc therapy in hippocampal avoidance whole-brain radiotherapy. J Appl Clin Med Phys 2024; 25:e14218. [PMID: 38013656 PMCID: PMC10795432 DOI: 10.1002/acm2.14218] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2023] [Revised: 09/06/2023] [Accepted: 11/12/2023] [Indexed: 11/29/2023] Open
Abstract
OBJECTIVE This study aimed to discuss the dosimetric advantages of helical tomotherapy (HT) and volumetric modulated arc therapy (VMAT) technology in hippocampal avoidance whole-brain radiotherapy and provide references for clinical selection of ideal radiotherapy technology. METHODS A total of 20 patients with hippocampal avoidance whole-brain radiotherapy were chosen randomly. Computed tomography (CT) and MRI scanning images were input into the treatment planning system (TPS). After the CT and enhanced magnetic resonance T1 weighted images were fused and registered, the same radiation therapy physician was invited to outline the tumor target volume. PTV-HS refers to the whole brain subtracted by 5 mm outward expansion of the hippocampus (HP). The prescribed dose was 30 Gy/10 fractions. HT and VMAT plans were designed for each patient in accordance with PTV. Under the premise that the 95% isodose curve covers the PTV, dose-volume histogram was applied to evaluate the PTV, conformal index (CI), heterogeneity index (HI), maximum dose (Dmax), mean dose (Dmean), minimum dose (Dmin) and absorbed doses of organs at risk (OARs) in HT and VMAT plans. Paired t-test was performed to compare the differences between two radiation therapy plans, and p < 0.05 was considered statistically significant. RESULTS These two plans had no significant difference in PTV-HS (max, min, and mean). However, the HI and CI of the HT plan were significantly better than those of the VMAT plan, showing statistically significant difference (p < 0.05). The HT plan was significantly superior to the VMAT plan in terms of the Dmax, Dmin, and Dmean of HP, left and right eye lens, left and right eye, and spinal cord, showing statistically significant difference (p < 0.05). The HT plan was also better than the VMAT plan in terms of the Dmax of the left optic nerve. However, the two plans showed no obvious differences in terms of the absorbed doses of the right optic nerve and brainstem, without statistical significance. CONCLUSIONS Compared with the VMAT plan of hippocampal avoidance, HT technology has significant dosimetric advantages. HT plans significantly decreased the radiation dose and radiation volume of OARs surrounding the target area (e.g., surrounding eye lens and eye, especially hippocampal avoidance area) while increasing the CI and HI of PTV dose in whole brain radiotherapy (WBRT) greatly, thus enabling the decrease in the incidence rate of radioactive nerve function impairment.
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Affiliation(s)
- Huai‐wen Zhang
- Department of RadiotherapyJiangxi Cancer HospitalThe Second Affiliated Hospital of Nanchang Medical College NHCKey Laboratory of Personalized Diagnosis and Treatment of Nasopharyngeal CarcinomaNanchangChina
- Department of Oncology, The third people's hospital of JingdezhenThe third people's hospital of Jingdezhen affiliated to Nanchang Medical CollegeJingdezhenChina
| | - Bo Hu
- Key Laboratory of Nondestructive Testing of Ministry of EducationNanchang HangKong UniversityNanchangChina
| | - Hao‐wen Pang
- Department of OncologyThe Affiliated Hospital of Southwest Medical UniversitySichuanChina
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Akdeniz Y, Ispir B. Whole-brain radiotherapy with hippocampus sparing and simultaneous integrated boost to metastases: A plan quality comparison study between Ethos, HyperArc, VMAT and Tomotherapy. Med Dosim 2023; 49:185-191. [PMID: 38101995 DOI: 10.1016/j.meddos.2023.11.004] [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: 08/13/2023] [Accepted: 11/10/2023] [Indexed: 12/17/2023]
Abstract
This study provides a concise and structured overview of a dosimetric comparison study conducted to assess the feasibility and effectiveness of 4 advanced radiotherapy techniques in treating brain metastases with hippocampus sparing and simultaneous integrated boost (HS-WBRT+SIB). Eleven patients with brain metastases previously treated with radiotherapy were included in the study. Planning CT scans with 2 mm slice thickness and MR imaging were used for contouring and dose prescription. The bilateral hippocampus and other organs at risk (OARs) were automatically contoured, and hippocampal avoidance regions (HAR) were defined as a 7 mm 3D expansion around the hippocampus. Gross tumor volume for each metastasis (GTVmet) and planning target volume for metastases (PTVmet) were delineated. The whole-brain CTV (CTVWB) and planning target volume for whole brain (PTVWB) were defined accordingly. Treatment planning and optimization were conducted using state-of-the-art radiotherapy techniques: Ethos, HyperArc, VMAT, and Tomotherapy. Tomotherapy achieved the highest D98% for PTVmet, indicating the best metastasis coverage. HyperArc plans showed the highest D98% for PTVWB, suggesting superior whole-brain coverage. Tomotherapy demonstrated significantly lower D98%, D2%, and Dmean values for the hippocampus, indicating its superiority in sparing the hippocampus. VMAT resulted in the lowest D2% values for the eyes, optic nerves, brainstem, and hypophysis, showing the best sparing of these critical structures. Tomotherapy consistently achieved lower Dmean values for parotids, oral cavity, and lips compared to the other techniques. The dosimetric comparison revealed distinct strengths and weaknesses for each radiotherapy technique. Tomotherapy excelled in sparing the hippocampus, while VMAT showed promise in sparing OARs. HyperArc plans demonstrated the best overall whole-brain coverage. These findings should guide clinicians in selecting the most suitable technique based on patient characteristics and institutional resources.
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Affiliation(s)
- Yucel Akdeniz
- Radiation Oncology Department, Acıbadem Adana Hospital, Adana, Turkey.
| | - Burcin Ispir
- Radiation Oncology Department, Acıbadem Ataşehir Hospital, İstanbul, Turkey
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Hardy SJ, Finkelstein A, Milano MT, Schifitto G, Sun H, Holley K, Usuki K, Weber MT, Zheng D, Seplaki CL, Janelsins M. Association of Radiation Dose to the Amygdala-Orbitofrontal Network with Emotion Recognition Task Performance in Patients with Low-Grade and Benign Brain Tumors. Cancers (Basel) 2023; 15:5544. [PMID: 38067248 PMCID: PMC10705220 DOI: 10.3390/cancers15235544] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2023] [Revised: 11/16/2023] [Accepted: 11/18/2023] [Indexed: 02/12/2024] Open
Abstract
BACKGROUND Although data are limited, difficulty in social cognition occurs in up to 83% of patients with brain tumors. It is unknown whether cranial radiation therapy (RT) dose to the amygdala-orbitofrontal network can impact social cognition. METHODS We prospectively enrolled 51 patients with low-grade and benign brain tumors planned for cranial RT. We assessed longitudinal changes on an emotion recognition task (ERT) that measures the ability to recognize emotional states by displaying faces expressing six basic emotions and their association with the RT dose to the amygdala-orbitofrontal network. ERT outcomes included the median time to choose a response (ERTOMDRT) or correct response (ERTOMDCRT) and total correct responses (ERTHH). RESULTS The RT dose to the amygdala-orbitofrontal network was significantly associated with longer median response times on the ERT. Increases in median response times occurred at lower doses than decreases in total correct responses. The medial orbitofrontal cortex was the most important variable on regression trees predicting change in the ERTOMDCRT. DISCUSSION This is, to our knowledge, the first study to show that off-target RT dose to the amygdala-orbitofrontal network is associated with performance on a social cognition task, a facet of cognition that has previously not been mechanistically studied after cranial RT.
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Affiliation(s)
- Sara J. Hardy
- Department of Radiation Oncology, University of Rochester, Rochester, NY 14620, USA; (M.T.M.); (D.Z.); (M.J.)
- Department of Neurology, University of Rochester Medical Center, Rochester, NY 14642, USA;
| | - Alan Finkelstein
- Department of Biomedical Engineering, University of Rochester, Rochester, NY 14627, USA;
- Center for Advanced Brain Imaging and Neurophysiology, University of Rochester Medical Center, Rochester, NY 14642, USA
| | - Michael T. Milano
- Department of Radiation Oncology, University of Rochester, Rochester, NY 14620, USA; (M.T.M.); (D.Z.); (M.J.)
| | - Giovanni Schifitto
- Department of Neurology, University of Rochester Medical Center, Rochester, NY 14642, USA;
- Department of Imaging Sciences, University of Rochester Medical Center, Rochester, NY 14642, USA;
| | - Hongying Sun
- Department of Surgery, Supportive Care in Cancer, University of Rochester Medical Center, Rochester, NY 14642, USA; (H.S.); (M.T.W.)
| | - Koren Holley
- Department of Imaging Sciences, University of Rochester Medical Center, Rochester, NY 14642, USA;
| | - Kenneth Usuki
- Department of Radiation Oncology, University of Rochester, Rochester, NY 14620, USA; (M.T.M.); (D.Z.); (M.J.)
| | - Miriam T. Weber
- Department of Surgery, Supportive Care in Cancer, University of Rochester Medical Center, Rochester, NY 14642, USA; (H.S.); (M.T.W.)
- Department of Obstetrics and Gynecology, University of Rochester Medical Center, Rochester, NY 14642, USA
| | - Dandan Zheng
- Department of Radiation Oncology, University of Rochester, Rochester, NY 14620, USA; (M.T.M.); (D.Z.); (M.J.)
| | - Christopher L. Seplaki
- Department of Public Health Sciences, University of Rochester Medical Center, Rochester, NY 14642, USA;
- Office for Aging Research and Health Services, University of Rochester Medical Center, Rochester, NY 14642, USA
| | - Michelle Janelsins
- Department of Radiation Oncology, University of Rochester, Rochester, NY 14620, USA; (M.T.M.); (D.Z.); (M.J.)
- Department of Surgery, Supportive Care in Cancer, University of Rochester Medical Center, Rochester, NY 14642, USA; (H.S.); (M.T.W.)
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Gondi V, Deshmukh S, Brown PD, Wefel JS, Armstrong TS, Tome WA, Gilbert MR, Konski A, Robinson CG, Bovi JA, Benzinger TLS, Roberge D, Kundapur V, Kaufman I, Shah S, Usuki KY, Baschnagel AM, Mehta MP, Kachnic LA. Sustained Preservation of Cognition and Prevention of Patient-Reported Symptoms With Hippocampal Avoidance During Whole-Brain Radiation Therapy for Brain Metastases: Final Results of NRG Oncology CC001. Int J Radiat Oncol Biol Phys 2023; 117:571-580. [PMID: 37150264 PMCID: PMC11070071 DOI: 10.1016/j.ijrobp.2023.04.030] [Citation(s) in RCA: 25] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2022] [Revised: 04/18/2023] [Accepted: 04/29/2023] [Indexed: 05/09/2023]
Abstract
PURPOSE Initial report of NRG Oncology CC001, a phase 3 trial of whole-brain radiation therapy plus memantine (WBRT + memantine) with or without hippocampal avoidance (HA), demonstrated neuroprotective effects of HA with a median follow-up of fewer than 8 months. Herein, we report the final results with complete cognition, patient-reported outcomes, and longer-term follow-up exceeding 1 year. METHODS AND MATERIALS Adult patients with brain metastases were randomized to HA-WBRT + memantine or WBRT + memantine. The primary endpoint was time to cognitive function failure, defined as decline using the reliable change index on the Hopkins Verbal Learning Test-Revised (HVLT-R), Controlled Oral Word Association, or the Trail Making Tests (TMT) A and B. Patient-reported symptom burden was assessed using the MD Anderson Symptom Inventory with Brain Tumor Module and EQ-5D-5L. RESULTS Between July 2015 and March 2018, 518 patients were randomized. The median follow-up for living patients was 12.1 months. The addition of HA to WBRT + memantine prevented cognitive failure (adjusted hazard ratio, 0.74, P = .016) and was associated with less deterioration in TMT-B at 4 months (P = .012) and HVLT-R recognition at 4 (P = .055) and 6 months (P = .011). Longitudinal modeling of imputed data showed better preservation of all HVLT-R domains (P < .005). Patients who received HA-WBRT + Memantine reported less symptom burden at 6 (P < .001 using imputed data) and 12 months (P = .026 using complete-case data; P < .001 using imputed data), less symptom interference at 6 (P = .003 using complete-case data; P = .0016 using imputed data) and 12 months (P = .0027 using complete-case data; P = .0014 using imputed data), and fewer cognitive symptoms over time (P = .043 using imputed data). Treatment arms did not differ significantly in overall survival, intracranial progression-free survival, or toxicity. CONCLUSIONS With median follow-up exceeding 1 year, HA during WBRT + memantine for brain metastases leads to sustained preservation of cognitive function and continued prevention of patient-reported neurologic symptoms, symptom interference, and cognitive symptoms with no difference in survival or toxicity.
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Affiliation(s)
- Vinai Gondi
- Northwestern Medicine Cancer Center Warrenville and Northwestern Medicine Proton Center, Department of Radiation Oncology, Warrenville, Illinois.
| | - Snehal Deshmukh
- NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania
| | - Paul D Brown
- Mayo Clinic, Department of Radiation Oncology, Rochester, Minnesota
| | - Jeffrey S Wefel
- University of Texas MD Anderson Cancer Center, Department of Neuro-Oncology, Houston, Texas
| | - Terri S Armstrong
- National Cancer Institute Center for Cancer Research, Bethesda, Maryland
| | - Wolfgang A Tome
- Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, New York
| | - Mark R Gilbert
- University of Texas MD Anderson Cancer Center, Department of Neuro-Oncology, Houston, Texas
| | - Andre Konski
- University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania
| | | | - Joseph A Bovi
- Froedtert and the Medical College of Wisconsin, Milwaukee, Wisconsin
| | | | | | | | - Isaac Kaufman
- Wayne State University/Karmanos Cancer Institute, Detroit, Michigan
| | - Sunjay Shah
- Delaware/Christiana Care National Cancer Institute Community Oncology Research Program, Wilmington, Delaware
| | | | | | | | - Lisa A Kachnic
- Columbia University, Vagelos Colleg of Physicians and Surgeons, New York, New York
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Mazzarella C, Chiesa S, Toppi L, Hohaus S, Gaudino S, D'Alo F, Dinapoli N, Davide R, Zinicola T, Bracci S, Martino A, Beghella Bartoli F, Lepre E, Bertolini R, Mariani S, Colosimo C, Frascino V, Mattiucci GC, Gambacorta MA, Valentini V, Balducci M. May we routinely spare hippocampal region in primary central nervous system lymphoma during whole brain radiotherapy? Radiat Oncol 2023; 18:161. [PMID: 37784190 PMCID: PMC10546760 DOI: 10.1186/s13014-023-02251-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2022] [Accepted: 03/27/2023] [Indexed: 10/04/2023] Open
Abstract
PURPOSE One of the main limiting factors of whole-brain radiation therapy (WBRT) for primary central nervous system lymphoma (PCNSL) is the impairment of neurocognitive functions (NCFs), which is mainly caused by radiation-induced injury to the hippocampus. With a view to preventing NCF impairment and personalizing treatment, we explored the feasibility of sparing the hippocampus during WBRT by correlating the sites of PCNSL lesions with the hippocampus. METHODS AND MATERIALS Pre-treatment MR images from patients who underwent WBRT between 2010 and January 2020-and post-radiotherapy images in cases of relapse-were imported into the Varian Eclipse treatment-planning system and registered with the simulation CT. We constructed three 3-dimensional envelopes around the hippocampus at distances of 5, 10 and 15 mm and also contoured primary lesions and recurrences. RESULTS We analyzed 43 patients with 66 primary lesions: 9/66 (13.6%) involved the hippocampus and 11/66 (16.7%) were located within 5 mm of it. Thirty-six lesions (54.5%) were situated more than 15 mm from the hippocampus, while 10/66 (15.2%) were between 5 and 15 mm from it. The most common location was in deep brain structures (31%). Thirty-five of the 66 lesions relapsed: in field in 14/35 (40%) and outfield in 21/35 (60%) in different sites. Globally, 16/35 recurrences (45.7%) were located in the hippocampus or within 5 mm of it. CONCLUSION These data show that routinely sparing the hippocampus is not feasible. This approach could be considered in selected patients, when the lesion is more than 15 mm from the hippocampus.
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Affiliation(s)
- Ciro Mazzarella
- UOC di Radioterapia Oncologica, Dipartimento Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, largo A. Gemelli, Rome, Italy.
| | - Silvia Chiesa
- UOC di Radioterapia Oncologica, Dipartimento Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, largo A. Gemelli, Rome, Italy
| | - Lucrezia Toppi
- UOC di Radioterapia Oncologica, Dipartimento Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, largo A. Gemelli, Rome, Italy
| | - Stefan Hohaus
- UOC di Ematologia, Dipartimento Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Rome, Italy
- Istituto di Ematologia, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Simona Gaudino
- UOC di Neuroradiologia, Dipartimento Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Rome, Italy
| | - Francesco D'Alo
- UOC di Ematologia, Dipartimento Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Rome, Italy
- Istituto di Ematologia, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Nicola Dinapoli
- UOC di Radioterapia Oncologica, Dipartimento Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, largo A. Gemelli, Rome, Italy
| | - Resta Davide
- UOC di Ematologia, Dipartimento Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Rome, Italy
| | - Tiziano Zinicola
- UOC di Radioterapia Oncologica, Dipartimento Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, largo A. Gemelli, Rome, Italy
| | - Serena Bracci
- UOC di Radioterapia Oncologica, Dipartimento Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, largo A. Gemelli, Rome, Italy
| | - Antonella Martino
- UOC di Radioterapia Oncologica, Dipartimento Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, largo A. Gemelli, Rome, Italy
| | - Francesco Beghella Bartoli
- UOC di Radioterapia Oncologica, Dipartimento Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, largo A. Gemelli, Rome, Italy
| | - Elisabetta Lepre
- UOC di Radioterapia Oncologica, Dipartimento Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, largo A. Gemelli, Rome, Italy
| | - Roberta Bertolini
- UOC di Radioterapia Oncologica, Dipartimento Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, largo A. Gemelli, Rome, Italy
| | - Silvia Mariani
- UOC di Radioterapia Oncologica, Dipartimento Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, largo A. Gemelli, Rome, Italy
| | - Cesare Colosimo
- Istituto di Radiologia, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Vincenzo Frascino
- UOC di Radioterapia Oncologica, Dipartimento Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, largo A. Gemelli, Rome, Italy
| | - Gian Carlo Mattiucci
- UOC di Radioterapia Oncologica, Dipartimento Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, largo A. Gemelli, Rome, Italy
- Istituto di Radiologia, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Maria Antonietta Gambacorta
- UOC di Radioterapia Oncologica, Dipartimento Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, largo A. Gemelli, Rome, Italy
- Istituto di Radiologia, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Vincenzo Valentini
- UOC di Radioterapia Oncologica, Dipartimento Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, largo A. Gemelli, Rome, Italy
- Istituto di Radiologia, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Mario Balducci
- UOC di Radioterapia Oncologica, Dipartimento Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, largo A. Gemelli, Rome, Italy
- Istituto di Radiologia, Università Cattolica del Sacro Cuore, Rome, Italy
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Price AT, Kang KH, Reynoso FJ, Laugeman E, Abraham CD, Huang J, Hilliard J, Knutson NC, Henke LE. In silico trial of simulation-free hippocampal-avoidance whole brain adaptive radiotherapy. Phys Imaging Radiat Oncol 2023; 28:100491. [PMID: 37772278 PMCID: PMC10523006 DOI: 10.1016/j.phro.2023.100491] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2023] [Revised: 08/26/2023] [Accepted: 08/31/2023] [Indexed: 09/30/2023] Open
Abstract
Background and Purpose Hippocampal-avoidance whole brain radiotherapy (HA-WBRT) can be a time-consuming process compared to conventional whole brain techniques, thus potentially limiting widespread utilization. Therefore, we evaluated the in silico clinical feasibility, via dose-volume metrics and timing, by leveraging a computed tomography (CT)-based commercial adaptive radiotherapy (ART) platform and workflow in order to create and deliver patient-specific, simulation-free HA-WBRT. Materials and methods Ten patients previously treated for central nervous system cancers with cone-beam computed tomography (CBCT) imaging were included in this study. The CBCT was the adaptive image-of-the-day to simulate first fraction on-board imaging. Initial contours defined on the MRI were rigidly matched to the CBCT. Online ART was used to create treatment plans at first fraction. Dose-volume metrics of these simulation-free plans were compared to standard-workflow HA-WBRT plans on each patient CT simulation dataset. Timing data for the adaptive planning sessions were recorded. Results For all ten patients, simulation-free HA-WBRT plans were successfully created utilizing the online ART workflow and met all constraints. The median hippocampi D100% was 7.8 Gy (6.6-8.8 Gy) in the adaptive plan vs 8.1 Gy (7.7-8.4 Gy) in the standard workflow plan. All plans required adaptation at first fraction due to both a failing hippocampal constraint (6/10 adaptive fractions) and sub-optimal target coverage (6/10 adaptive fractions). Median time for the adaptive session was 45.2 min (34.0-53.8 min). Conclusions Simulation-free HA-WBRT, with commercially available systems, was clinically feasible via plan-quality metrics and timing, in silico.
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Affiliation(s)
- Alex T. Price
- Corresponding author at: Department of Radiation Oncology, University Hospitals Seidman Cancer Center, 11100 Euclid Ave, Cleveland OH 44106, USA
| | - Kylie H. Kang
- Department of Radiation Oncology, Washington University School of Medicine, 4511 Forest Park Ave, St. Louis, MO 63108, USA
| | - Francisco J. Reynoso
- Department of Radiation Oncology, Washington University School of Medicine, 4511 Forest Park Ave, St. Louis, MO 63108, USA
| | - Eric Laugeman
- Department of Radiation Oncology, Washington University School of Medicine, 4511 Forest Park Ave, St. Louis, MO 63108, USA
| | - Christopher D. Abraham
- Department of Radiation Oncology, Washington University School of Medicine, 4511 Forest Park Ave, St. Louis, MO 63108, USA
| | - Jiayi Huang
- Department of Radiation Oncology, Washington University School of Medicine, 4511 Forest Park Ave, St. Louis, MO 63108, USA
| | - Jessica Hilliard
- Department of Radiation Oncology, Washington University School of Medicine, 4511 Forest Park Ave, St. Louis, MO 63108, USA
| | - Nels C. Knutson
- Department of Radiation Oncology, Washington University School of Medicine, 4511 Forest Park Ave, St. Louis, MO 63108, USA
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Pertz M, Schlömer S, Seidel C, Hentschel B, Löffler M, Schackert G, Krex D, Juratli T, Tonn JC, Schnell O, Vatter H, Simon M, Westphal M, Martens T, Sabel M, Bendszus M, Dörner N, Wick A, Fliessbach K, Hoppe C, Klingner M, Felsberg J, Reifenberger G, Gramatzki D, Weller M, Schlegel U. Long-term neurocognitive function and quality of life after multimodal therapy in adult glioma patients: a prospective long-term follow-up. J Neurooncol 2023; 164:353-366. [PMID: 37648934 PMCID: PMC10522752 DOI: 10.1007/s11060-023-04419-y] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2023] [Accepted: 08/09/2023] [Indexed: 09/01/2023]
Abstract
PURPOSE Multimodal therapies have significantly improved prognosis in glioma. However, in particular radiotherapy may induce long-term neurotoxicity compromising patients' neurocognition and quality of life. The present prospective multicenter study aimed to evaluate associations of multimodal treatment with neurocognition with a particular focus on hippocampal irradiation. METHODS Seventy-one glioma patients (WHO grade 1-4) were serially evaluated with neurocognitive testing and quality of life questionnaires. Prior to (baseline) and following further treatment (median 7.1 years [range 4.6-11.0] after baseline) a standardized computerized neurocognitive test battery (NeuroCog FX) was applied to gauge psychomotor speed and inhibition, verbal short-term memory, working memory, verbal and non-verbal memory as well as verbal fluency. Mean ipsilateral hippocampal radiation dose was determined in a subgroup of 27 patients who received radiotherapy according to radiotherapy plans to evaluate its association with neurocognition. RESULTS Between baseline and follow-up mean performance in none of the cognitive domains significantly declined in any treatment modality (radiotherapy, chemotherapy, combined radio-chemotherapy, watchful-waiting), except for selective attention in patients receiving chemotherapy alone. Apart from one subtest (inhibition), mean ipsilateral hippocampal radiation dose > 50 Gy (Dmean) as compared to < 10 Gy showed no associations with long-term cognitive functioning. However, patients with Dmean < 10 Gy showed stable or improved performance in all cognitive domains, while patients with > 50 Gy numerically deteriorated in 4/8 domains. CONCLUSIONS Multimodal glioma therapy seems to affect neurocognition less than generally assumed. Even patients with unilateral hippocampal irradiation with > 50 Gy showed no profound cognitive decline in this series.
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Affiliation(s)
- Milena Pertz
- Department of Medical Psychology and Medical Sociology, Ruhr University Bochum, Universitätsstraße 105, 44789, Bochum, Germany.
- Department of Neurology, University Hospital Knappschaftskrankenhaus, Ruhr University Bochum, Bochum, Germany.
| | - Sabine Schlömer
- Department of Neurology, University Hospital Knappschaftskrankenhaus, Ruhr University Bochum, Bochum, Germany
| | - Clemens Seidel
- Department of Radiation Oncology, University Hospital Leipzig, Leipzig, Germany
| | - Bettina Hentschel
- Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany
| | - Markus Löffler
- Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany
| | - Gabriele Schackert
- Department of Neurosurgery, University Hospital Carl Gustav Carus, Technical University of Dresden, Dresden, Germany
| | - Dietmar Krex
- Department of Neurosurgery, University Hospital Carl Gustav Carus, Technical University of Dresden, Dresden, Germany
| | - Tareq Juratli
- Department of Neurosurgery, University Hospital Carl Gustav Carus, Technical University of Dresden, Dresden, Germany
| | - Joerg Christian Tonn
- Department of Neurosurgery, University Hospital, Ludwig Maximilians University of Munich, Munich, Germany
| | - Oliver Schnell
- Department of Neurosurgery, University Hospital, Ludwig Maximilians University of Munich, Munich, Germany
- Department of Neurosurgery, Medical Center, University of Freiburg, Freiburg, Germany
| | - Hartmut Vatter
- Department of Neurosurgery, University Hospital Bonn, Bonn, Germany
| | - Matthias Simon
- Department of Neurosurgery, University Hospital Bonn, Bonn, Germany
- Department of Neurosurgery, Medical Center Bethel, University Hospital Bielefeld, Bielefeld, Germany
| | - Manfred Westphal
- Department of Neurosurgery, University Hospital Hamburg-Eppendorf, Hamburg, Germany
| | - Tobias Martens
- Department of Neurosurgery, University Hospital Hamburg-Eppendorf, Hamburg, Germany
- Department of Neurosurgery, Medical Center Asklepios St. Georg, Hamburg, Germany
| | - Michael Sabel
- Department of Neurosurgery, Heinrich Heine University Medical Faculty and University Hospital Düsseldorf, Düsseldorf, Germany
| | - Martin Bendszus
- Department of Neuroradiology, Medical Center of Neurology, University Hospital Heidelberg, Heidelberg, Germany
| | - Nils Dörner
- Department of Neuroradiology, Medical Center of Neurology, University Hospital Heidelberg, Heidelberg, Germany
- Institute for Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, Essen, Germany
| | - Antje Wick
- Neurology Clinic and National Centre for Tumour Diseases, University Hospital Heidelberg, Heidelberg, Germany
- Clinical Cooperation Unit Neurooncology, German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), Heidelberg, Germany
| | - Klaus Fliessbach
- Department of Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, Bonn, Germany
| | - Christian Hoppe
- Department of Epileptology, University Hospital Bonn, Bonn, Germany
| | - Marcel Klingner
- Department of Radiation Oncology, University Hospital Leipzig, Leipzig, Germany
| | - Jörg Felsberg
- Institute of Neuropathology, Heinrich Heine University Medical Faculty and University Hospital Düsseldorf, Düsseldorf, Germany
| | - Guido Reifenberger
- Institute of Neuropathology, Heinrich Heine University Medical Faculty and University Hospital Düsseldorf, Düsseldorf, Germany
| | - Dorothee Gramatzki
- Department of Neurology, University Hospital and University of Zurich, Zurich, Switzerland
| | - Michael Weller
- Department of Neurology, University Hospital and University of Zurich, Zurich, Switzerland
- Department of General Neurology, University Hospital Tübingen, Tübingen, Germany
| | - Uwe Schlegel
- Department of Neurology, University Hospital Knappschaftskrankenhaus, Ruhr University Bochum, Bochum, Germany
- Department of Neurology, Hirslanden Hospital, Zurich, Switzerland
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Deepsikha G, Maji T, Lahiri D, Roy S, Bhanja S, Rangineni S, Ray DK, Mohanta BK, Misra DK, De P. Hippocampal avoidance whole brain radiotherapy in brain metastasis using volumetric modulated arc therapy: experience from a Regional Cancer Centre of Eastern India. Rep Pract Oncol Radiother 2023; 28:468-477. [PMID: 37795235 PMCID: PMC10547418 DOI: 10.5603/rpor.a2023.0048] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2022] [Accepted: 07/19/2023] [Indexed: 10/06/2023] Open
Abstract
Background Whole-brain radiotherapy is associated with neurocognitive decline and decreased quality-of-life (QOL) among survivors of brain metastasis. Hippocampal-avoidance whole-brain radiotherapy (HA-WBRT) has shown advantage in delaying or preventing the neurocognitive decline while maintaining disease control. This study was done to assess the benefits and feasibility of HA-WBRT in patients with cerebral metastasis in terms of preservation of neurocognitive function and quality of life. Materials and methods 27 patients with brain metastasis treated by HA-WBRT and having the records of detailed neurocognitive-assessments were analysed from the database of our hospital. The patients were treated with HA-WBRT to a total dose of 30 Gy in 10 fractions with LINAC based IMRT using the VMAT technique. Cognitive function assessment was carried out using "Examination of the Cognitive Functions" scale provided by Bangur-Institute-of-Neurosciences, Kolkata, 2 weeks prior to radiotherapy and post-treatment two-monthly up to 6 months followed by every 3 months till the last follow up. QOL was assessed at the same interval using the Functional Assessment of Cancer Therapy with Brain Subscale (FACT-BR). Follow-up was done till the date of death. Results Mean relative cognitive decline percentage decreased over subsequent follow-up visits and was 13% (SD ± 6%), 5% (SD ± 5%), 5% (SD ± 9%) and 2% (SD ± 12%) at 2 months, 6 months, 9 months and 12 months, respectively (p ≤ 0.05). Statistically significant improvement was seen in the mean social-wellbeing (SWB) parameter of QOL (8%. ± 13%, 12%. ± 16%, 7%. ± 20%, no change at 2 months, 4 months, 6 months and 9 months, respectively) (p ≤ 0.05). Mean relative decline in the Emotional-Well Being (EWB) parameter was significant only at 12 months and was 20% (SD ± 35%) (p = 0.04). Mean FACT-BR total Score showed a slight decrease till 9 months from baseline, and then showed a slight improvement up to 12 months. Conclusion HA-WBRT is feasible with LINAC-based IMRT using the VMAT technique and beneficial to the patients in preserving neurocognitive function and quality of life without compromising disease control.
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Affiliation(s)
- Goyel Deepsikha
- Radiation Oncology, Chittaranjan National Cancer Institute, Kolkata, India
| | - Tapas Maji
- Radiation Oncology, Chittaranjan National Cancer Institute, Kolkata, India
| | - Debarshi Lahiri
- Radiation Oncology, Chittaranjan National Cancer Institute, Kolkata, India
| | - Sanjoy Roy
- Radiation Oncology, Chittaranjan National Cancer Institute, Kolkata, India
| | - Sayoni Bhanja
- Radiation Oncology, Chittaranjan National Cancer Institute, Kolkata, India
| | | | - Dilip Kumar Ray
- Radiation Oncology, Chittaranjan National Cancer Institute, Kolkata, India
| | | | - Dilip Kumar Misra
- Radiation Oncology, Chittaranjan National Cancer Institute, Kolkata, India
| | - Palas De
- Radiation Oncology, Chittaranjan National Cancer Institute, Kolkata, India
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Wang X, Chen J, Lei Z, Chen H, Zhang Y, Liu G, Li S, Zheng Z, Wang H. Propensity score-matched analysis comparing hippocampus-avoidance whole-brain radiotherapy plus simultaneous integrated boost with hippocampus‑avoidance whole-brain radiotherapy alone for multiple brain metastases-a retrospective study in multiple institutions. BMC Cancer 2023; 23:796. [PMID: 37620791 PMCID: PMC10464036 DOI: 10.1186/s12885-023-11286-3] [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: 10/21/2022] [Accepted: 08/09/2023] [Indexed: 08/26/2023] Open
Abstract
BACKGROUND The optimal treatment for multiple brain metastases has been recently controversially discussed.This study was aimed to explore the feasibility of Hippocampus-Avoidance Whole-Brain Radiotherapy plus a simultaneous integrated boost (HA-WBRT + SIB) in patients with multiple brain metastases and assess tumor control in comparison with Hippocampus-Avoidance Whole-Brain Radiotherapy (HA-WBRT) alone for brain metastases. METHODS In this study, 63 patients with multiple brain metastases (≥ 4 metastases) had undergone HA-WBRT + SIB between January 2016 and December 2020 in the observation group:HA-WBRT (30 Gy in 12 fractions, the maximum dose of the hippocampus ≤ 14 Gy) plus a simultaneous integrated boost (48 Gy in 12 fractions) for brain metastases.Overall Survival (OS), Median survival,intracranial control (IC = control within the entire brain), intracranial progression-free survival (iPFS) and adverse events were compared with the control group (a HA-WBRT retrospective cohort) by propensity score matching analysis. RESULTS After 1:1 propensity score matching,there were 56 patients in each group (the observation group, the control group). OS, median survival and iPFS were significantly longer in the observation group (18.4 vs. 10.9 months, P<0.001), (13.0 vs. 8.0 months, P<0.001), (13.9 vs.7.8 months, P<0.001). In comparison of 1-year-IC rates, the observation group also demonstrated higher than the control group (51.8% vs. 21.4%, P = 0.002), respectively. Seven hippocampal metastases were found in the control group (4/56,7.1%) and the observation group (3/56,5.4%) after HA-WBRT. The death rate of intracranial progression were 23.2% in the observation group and 37.5% in the control group.All adverse events were not significant difference between the two groups (P>0.05). CONCLUSIONS HA-WBRT + SIB resulted in better OS,median survival, IC, iPFS, an acceptable risk of radiation response, and a potential way of declining neurocognitive adverse events, which may be a better treatment for patients with multiple brain metastases.
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Affiliation(s)
- Xiaoliang Wang
- Department of Radiotherapy, The Third Hospital of Zhangzhou, Zhangzhou Fujian, 363005, China.
| | - Jinping Chen
- Department of Radiation Oncology, Army 73rd Group Military Hospital, Xiamen Fujian, 361003, China
| | - Zhanquan Lei
- Department of Radiation Oncology, FuJian Children's Hospital, Fuzhou Fujian, 350100, China
| | - Haihong Chen
- Information Department, Army 73rd Group Military Hospital, Xiamen Fujian, 361003, China
| | - Yufang Zhang
- Department of Radiation Oncology, XiaMen ChangGung Hospital, Xiamen Fujian, 361028, China
| | - Gang Liu
- Medical Examination Center, Army 73rd Group Military Hospital, Xiamen Fujian, 361003, China
| | - Shaomin Li
- Department of Radiation Oncology, XiaMen ChangGung Hospital, Xiamen Fujian, 361028, China
| | - Zhenhua Zheng
- Department of Radiation Oncology, XiaMen ChangGung Hospital, Xiamen Fujian, 361028, China
| | - Hui Wang
- Department of Radiation Oncology, Zhongshan Hospital Affiliated to Xiamen University, Xiamen, 361003, Fujian, China
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Xu F, Ou D, Qi W, Wang S, Han Y, Cai G, Cao L, Xu C, Chen JY. Impact of multidisciplinary team on the pattern of care for brain metastasis from breast cancer. Front Oncol 2023; 13:1160802. [PMID: 37664027 PMCID: PMC10471195 DOI: 10.3389/fonc.2023.1160802] [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: 05/12/2023] [Accepted: 07/18/2023] [Indexed: 09/05/2023] Open
Abstract
Purpose The aim of this study was to explore how a multidisciplinary team (MDT) affects patterns of local or systematic treatment. Methods We retrospectively reviewed the data of consecutive patients in the breast cancer with brain metastases (BCBM) database at our institution from January 2011 to April 2021. The patients were divided into an MDT group and a non-MDT group. Results A total of 208 patients were analyzed, including 104 each in the MDT and non-MDT groups. After MDT, 56 patients (53.8%) were found to have intracranial "diagnosis upgrade". In the matched population, patients in the MDT group recorded a higher proportion of meningeal metastases (14.4% vs. 4.8%, p = 0.02), symptomatic tumor progression (11.5% vs. 5.8%, p = 0.04), and an increased number of occurrences of brain metastases (BM) progression (p < 0.05). Attending MDT was an independent factor associated with ≥2 courses of intracranial radiotherapy (RT) [odds ratio (OR) 5.4, 95% confidence interval (CI): 2.7-10.9, p < 0.001], novel RT technique use (7.0, 95% CI 3.5-14.0, p < 0.001), and prospective clinical research (OR 5.7, 95% CI 2.4-13.4, p < 0.001). Conclusion Patients with complex conditions are often referred for MDT discussions. An MDT may improve the qualities of intracranial RT and systemic therapy, resulting in benefits of overall survival for BC patients after BM. This encourages the idea that treatment recommendations for patients with BMBC should be discussed within an MDT.
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Affiliation(s)
| | | | | | | | | | | | | | | | - Jia-Yi Chen
- Department of Radiation Oncology, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China
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Chen VE, Kim M, Nelson N, Kim IK, Shi W. Cost-effectiveness analysis of 3 radiation treatment strategies for patients with multiple brain metastases. Neurooncol Pract 2023; 10:344-351. [PMID: 37457226 PMCID: PMC10346394 DOI: 10.1093/nop/npac093] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2023] Open
Abstract
Background Patients diagnosed with multiple brain metastases often survive for less than 2 years, and clinicians must carefully evaluate the impact of interventions on quality of life. Three types of radiation treatment are widely accepted for patients with multiple brain metastases: Whole brain radiation therapy (WBRT), hippocampal avoidance whole-brain radiation therapy (HA-WBRT), and stereotactic radiosurgery (SRS). WBRT, the standard option, is less costly than its newer alternatives but causes more severe adverse effects such as memory loss. To determine whether the cost-effectiveness ratio of HA-WBRT and SRS are superior to WBRT, we used published data to simulate cases of multiple brain metastases. Methods We designed a Markov model using data from previously published studies to simulate the disease course of patients with 5 to 15 brain metastases and determine the cost-effectiveness of HA-WBRT and SRS relative to WBRT. Incremental cost-effectiveness ratios (ICERs) were calculated and compared against a willingness-to-pay threshold of $100 000 per quality-adjusted life year. Results SRS met the threshold for cost-effectiveness, with ICERs ranging $41 198-$54 852 for patients with 5 to 15 brain metastases; however, HA-WBRT was not cost-effective, with an ICER of $163 915 for all simulated patients. Model results were robust to sensitivity analyses. Conclusions We propose that SRS, but not HA-WBRT, should be offered to patients with multiple brain metastases as a treatment alternative to standard WBRT. Incorporating these findings into clinical practice will help promote patient-centered care and decrease national healthcare expenditures, thereby addressing issues around health equity and access to care.
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Affiliation(s)
- Victor Eric Chen
- Department of Radiation Oncology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
| | - Minchul Kim
- Center for Outcomes Research, University of Illinois College of Medicine at Peoria, Peoria, Illinois, USA
| | - Nicolas Nelson
- Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
| | - Inkyu Kevin Kim
- College of Population Health, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
| | - Wenyin Shi
- Department of Radiation Oncology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
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Nieder C, Andratschke NH, Grosu AL. Brain Metastases: Is There Still a Role for Whole-Brain Radiation Therapy? Semin Radiat Oncol 2023; 33:129-138. [PMID: 36990630 DOI: 10.1016/j.semradonc.2023.01.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/29/2023]
Abstract
Whole-brain radiation therapy (WBRT) has commonly been prescribed to palliate symptoms from brain metastases, to reduce the risk of local relapse after surgical resection, and to improve distant brain control after resection or radiosurgery. While targeting micrometastases throughout the brain can be considered advantageous, the simultaneous exposure of healthy brain tissue might cause adverse events. Attempts to mitigate the risk of neurocognitive decline after WBRT include the selective avoidance of the hippocampi, among others. Besides selective dose reduction, dose escalation to boost volumes, for example, simultaneous integrated boost, aiming at increased tumor control probability is technically feasible. While up-front radiotherapy for newly diagnosed brain metastases often employs radiosurgery or other techniques targeting visible lesions only, sequential (delayed) salvage treatment with WBRT might still become necessary. In addition, the presence of leptomeningeal tumors or very widespread parenchymatous brain metastases might prompt clinicians to prescribe early WBRT.
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Chiang PY, Hung CH, Chang CC, Lee CY, Wang YW, Tsang YW. Hippocampal-sparing whole-brain radiotherapy under coplanar or noncoplanar VMAT. Med Dosim 2023:S0958-3947(23)00021-3. [PMID: 37012163 DOI: 10.1016/j.meddos.2023.02.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2022] [Revised: 02/07/2023] [Accepted: 02/23/2023] [Indexed: 04/04/2023]
Abstract
Whole-brain radiotherapy (WBRT) can alleviate symptoms in patients with brain metastases. However, WBRT may damage the hippocampus. Volumetric modulated arc therapy (VMAT) can achieve a suitable coverage of the target region and a more conforming dose distribution whereas decreasing the dose to organs-at-risk (OARs). Herein, we aimed to compare the differences between treatment plans utilizing coplanar VMAT and noncoplanar VMAT in hippocampal-sparing WBRT (HS-WBRT). Ten patients were included in this study. For each patient, the Eclipse A10 treatment planning system was used to generate 1 coplanar VMAT (C-VMAT) and 2 noncoplanar VMAT treatment plans with various beam angles (noncoplanar VMAT A [NC-A] and noncoplanar VMAT B [NC-B]) for HS-WBRT. The prescribed dose was 30 Gy in 12 fractions. Treatment plans were established based on the OAR dose constraints of the Radiation Therapy Oncology Group 0933 (RTOG 0933). Parameters such as the global maximum dose, dose conformity, dose homogeneity of plans, and OAR doses were evaluated. The maximum biologically equivalent doses in 2-Gy fractions (EQD2) of OARs in C-VMAT were 9.17 ± 0.61, 42.79 ± 2.00, and 42.84 ± 3.52 Gy in the hippocampus, brain stem, and optic chiasm, respectively, which were the lowest among the 3 treatment plans. There was no significant difference in dose conformity among the 3 treatment plans. However, NC-A had a slightly better conformity than C-VMAT and NC-B. NC-A had the best homogeneity, and NC-B had the worst homogeneity (p = 0.042). NC-A and NC-B had the lowest and highest global dose maximum, respectively. Therefore, NC-A, which had an intermediate performance in terms of OAR doses, had the best quality parameters. We used the quality score table based on the p-value to evaluate the significant difference between each treatment technique from the multiparameter results. In terms of treatment plan parameters, only NC-A received a score of 2; for OAR doses, C-VMAT, NC-A, and NC-B received a score of 6, 3, and 5, respectively. For the overall evaluation, C-VMAT, NC-A, and NC-B received a total score of 6, 5, and 5, respectively. Rather than noncoplanar VMAT, 3 full-arc C-VMATs should be utilized in HS-WBRT. C-VMAT can simultaneously maintain treatment plan quality and decrease patient alignment time and total treatment time.
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Schmidt MC, Abraham CD, Huang J, Robinson CG, Hugo G, Knutson NC, Sun B, Raranje C, Sajo E, Zygmanski P, Jandel M, Szentivanyi P, Hilliard J, Hamilton J, Reynoso FJ. Clinical application of a template-guided automated planning routine. J Appl Clin Med Phys 2023; 24:e13837. [PMID: 36347220 PMCID: PMC10018666 DOI: 10.1002/acm2.13837] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2022] [Revised: 06/06/2022] [Accepted: 10/11/2022] [Indexed: 11/09/2022] Open
Abstract
PURPOSE Determine the dosimetric quality and the planning time reduction when utilizing a template-based automated planning application. METHODS A software application integrated through the treatment planning system application programing interface, QuickPlan, was developed to facilitate automated planning using configurable templates for contouring, knowledge-based planning structure matching, field design, and algorithm settings. Validations are performed at various levels of the planning procedure and assist in the evaluation of readiness of the CT image, structure set, and plan layout for automated planning. QuickPlan is evaluated dosimetrically against 22 hippocampal-avoidance whole brain radiotherapy patients. The required times to treatment plan generation are compared for the validations set as well as 10 prospective patients whose plans have been automated by QuickPlan. RESULTS The generations of 22 automated treatment plans are compared against a manual replanning using an identical process, resulting in dosimetric differences of minor clinical significance. The target dose to 2% volume and homogeneity index result in significantly decreased values for automated plans, whereas other dose metric evaluations are nonsignificant. The time to generate the treatment plans is reduced for all automated plans with a median difference of 9' 50″ ± 4' 33″. CONCLUSIONS Template-based automated planning allows for reduced treatment planning time with consistent optimization structure creation, treatment field creation, plan optimization, and dose calculation with similar dosimetric quality. This process has potential expansion to numerous disease sites.
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Affiliation(s)
- Matthew C Schmidt
- Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri, USA.,Department of Physics, University of Massachusetts Lowell, Lowell, Massachusetts, USA
| | - Christopher D Abraham
- Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri, USA
| | - Jiayi Huang
- Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri, USA
| | - Clifford G Robinson
- Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri, USA
| | - Geoffrey Hugo
- Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri, USA
| | - Nels C Knutson
- Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri, USA
| | - Baozhou Sun
- Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri, USA
| | - Chipo Raranje
- Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri, USA
| | - Erno Sajo
- Department of Physics, University of Massachusetts Lowell, Lowell, Massachusetts, USA
| | - Piotr Zygmanski
- Brigham and Women's/Dana Farber Cancer Institute/Harvard Medical School, Boston, Massachusetts, USA
| | - Marian Jandel
- Department of Physics, University of Massachusetts Lowell, Lowell, Massachusetts, USA
| | | | - Jessica Hilliard
- Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri, USA
| | - Jessica Hamilton
- Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri, USA
| | - Francisco J Reynoso
- Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri, USA
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Baliga S, Adams JA, Bajaj BVM, Van Benthuysen L, Daartz J, Gallotto SL, Lewy JR, DeNunzio N, Weyman EA, Lawell MP, Palmer JD, Yeap BY, Ebb DH, Huang MS, Perry AF, MacDonald SM, Jones RM, Tarbell NJ, Yock TI. Patterns of failure in pediatric medulloblastoma and implications for hippocampal sparing. Cancer 2023; 129:764-770. [PMID: 36504293 PMCID: PMC10107770 DOI: 10.1002/cncr.34574] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2022] [Revised: 10/04/2022] [Accepted: 10/10/2022] [Indexed: 12/14/2022]
Abstract
BACKGROUND Hippocampal avoidance (HA) has been shown to preserve cognitive function in adult patients with cancer treated with whole-brain radiation therapy for brain metastases. However, the feasibility of HA in pediatric patients with brain tumors has not been explored because of concerns of increased risk of relapse in the peri-hippocampal region. Our aim was to determine patterns of recurrence and incidence of peri-hippocampal relapse in pediatric patients with medulloblastoma (MB). METHODS AND MATERIALS We identified pediatric patients with MB treated with protons between 2002 and 2016 and who had recurrent disease. To estimate the risk of peri-hippocampal recurrence, three hippocampal zones (HZs) were delineated corresponding to ≤5 mm (HZ-1), 6 to 10 mm (HZ-2), and >10 mm (HZ-3) distance of the recurrence from the contoured hippocampi. To determine the feasibility of HA, three standard-risk patients with MB were planned using either volumetric-modulated arc therapy (VMAT) or intensity-modulated proton therapy (IMPT) plans. RESULTS Thirty-eight patients developed a recurrence at a median of 1.6 years. Of the 25 patients who had magnetic resonance imaging of the recurrence, no patients failed within the hippocampus and only two patients failed within HZ-1. The crude incidence of peri-hippocampal failure was 8%. Both HA-VMAT and HA-IMPT plans were associated with significantly reduced mean dose to the hippocampi (p < .05). HA-VMAT and HA-IMPT plans were associated with decreased percentage of the third and lateral ventricles receiving the prescription craniospinal dose of 23.4 Gy. CONCLUSIONS Peri-hippocampal failures are uncommon in pediatric patients with MB. Hippocampal avoidance should be evaluated in a prospective cohort of pediatric patients with MB. PLAIN LANGUAGE SUMMARY In this study, the patterns of disease recurrence in patients with a pediatric brain tumor known as medulloblastoma treated with proton radiotherapy were examined. The majority of failures occur outside of an important structure related to memory formation called the hippocampus. Hippocampal sparing radiation plans using proton radiotherapy were generated and showed that dose to the hippocampus was able to be significantly reduced. The study provides the rationale to explore hippocampal sparing in pediatric medulloblastoma in a prospective clinical trial.
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Affiliation(s)
- Sujith Baliga
- Department of Radiation Oncology, Ohio State University Wexner Medical Center, Columbus, Ohio, USA
| | - Judith A Adams
- Department of Radiation Oncology, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts, USA
| | - Benjamin V M Bajaj
- Department of Radiation Oncology, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts, USA
| | - Liam Van Benthuysen
- Department of Radiation Oncology, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts, USA
| | - Juliane Daartz
- Department of Radiation Oncology, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts, USA
| | - Sara L Gallotto
- Department of Radiation Oncology, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts, USA
| | - Jacqueline R Lewy
- Department of Radiation Oncology, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts, USA
| | - Nicholas DeNunzio
- Department of Radiation Oncology, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts, USA
| | - Elizabeth A Weyman
- Department of Radiation Oncology, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts, USA
| | - Miranda P Lawell
- Department of Radiation Oncology, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts, USA
| | - Joshua D Palmer
- Department of Radiation Oncology, Ohio State University Wexner Medical Center, Columbus, Ohio, USA
| | - Beow Y Yeap
- Department of Radiation Oncology, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts, USA
| | - David H Ebb
- Department of Pediatric Hematology Oncology, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Mary S Huang
- Department of Pediatric Hematology Oncology, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Alisa F Perry
- Department of Radiation Oncology, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts, USA
| | - Shannon M MacDonald
- Department of Radiation Oncology, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts, USA
| | - Robin M Jones
- Department of Pediatric Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Nancy J Tarbell
- Department of Radiation Oncology, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts, USA
| | - Torunn I Yock
- Department of Radiation Oncology, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts, USA
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Gram D, Brodin NP, Björk-Eriksson T, Nysom K, Munck Af Rosenschöld P. The risk of radiation-induced neurocognitive impairment and the impact of sparing the hippocampus during pediatric proton cranial irradiation. Acta Oncol 2023; 62:134-140. [PMID: 36847433 DOI: 10.1080/0284186x.2023.2176253] [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] [Indexed: 03/01/2023]
Abstract
BACKGROUND AND PURPOSE Hippocampus is a central component for neurocognitive function and memory. We investigated the predicted risk of neurocognitive impairment of craniospinal irradiation (CSI) and the deliverability and effects of hippocampal sparing. The risk estimates were derived from published NTCP models. Specifically, we leveraged the estimated benefit of reduced neurocognitive impairment with the risk of reduced tumor control. MATERIAL AND METHODS For this dose planning study, a total of 504 hippocampal sparing intensity modulated proton therapy (HS-IMPT) plans were generated for 24 pediatric patients whom had previously received CSI. Plans were evaluated with respect to target coverage and homogeneity index to target volumes, maximum and mean dose to OARs. Paired t-tests were used to compare hippocampal mean doses and normal tissue complication probability estimates. RESULTS The median mean dose to the hippocampus could be reduced from 31.3 GyRBE to 7.3 GyRBE (p < .001), though 20% of these plans were not considered clinically acceptable as they failed one or more acceptance criterion. Reducing the median mean hippocampus dose to 10.6 GyRBE was possible with all plans considered as clinically acceptable treatment plans. By sparing the hippocampus to the lowest dose level, the risk estimation of neurocognitive impairment could be reduced from 89.6%, 62.1% and 51.1% to 41.0% (p < .001), 20.1% (p < .001) and 29.9% (p < .001) for task efficiency, organization and memory, respectively. Estimated tumor control probability was not adversely affected by HS-IMPT, ranging from 78.5 to 80.5% for all plans. CONCLUSIONS We present estimates of potential clinical benefit in terms of neurocognitive impairment and demonstrate the possibility of considerably reducing neurocognitive adverse effects, minimally compromising target coverage locally using HS-IMPT.
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Affiliation(s)
- Daniel Gram
- Department of Oncology - Section of Radiotherapy, Rigshospitalet, Copenhagen, Denmark.,Niels Bohr Institute, University of Copenhagen, Copenhagen, Denmark.,Department of Clinical Oncology and Palliative Care, Radiotherapy, Zealand University Hospital, Næstved, Denmark
| | - N Patrik Brodin
- Institute for Onco-Physics, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY, USA
| | - Thomas Björk-Eriksson
- Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy at the University of Gothenburg, Sweden.,Regional Cancer Centre West, Gothenburg, Sweden
| | - Karsten Nysom
- Department of Paediatrics and Adolescent Medicine, The Juliane Marie Center, Rigshospitalet, Copenhagen, Denmark
| | - Per Munck Af Rosenschöld
- Niels Bohr Institute, University of Copenhagen, Copenhagen, Denmark.,Radiation Physics - Department of Hematology, Oncology and Radiation Physics, Skåne University Hospital, Lund, Sweden.,Medical Radiation Physics, Department of Clinical Sciences, Lund University, Lund, Sweden
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Hardy SJ, Finkelstein AJ, Tivarus M, Culakova E, Mohile N, Weber M, Lin E, Zhong J, Usuki K, Schifitto G, Milano M, Janelsins-Benton MC. Cognitive and neuroimaging outcomes in individuals with benign and low-grade brain tumours receiving radiotherapy: a protocol for a prospective cohort study. BMJ Open 2023; 13:e066458. [PMID: 36792323 PMCID: PMC9933762 DOI: 10.1136/bmjopen-2022-066458] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2022] [Accepted: 01/27/2023] [Indexed: 02/17/2023] Open
Abstract
INTRODUCTION Radiation-induced cognitive decline (RICD) occurs in 50%-90% of adult patients 6 months post-treatment. In patients with low-grade and benign tumours with long expected survival, this is of paramount importance. Despite advances in radiation therapy (RT) treatment delivery, better understanding of structures important for RICD is necessary to improve cognitive outcomes. We hypothesise that RT may affect network topology and microstructural integrity on MRI prior to any gross anatomical or apparent cognitive changes. In this longitudinal cohort study, we aim to determine the effects of RT on brain structural and functional integrity and cognition. METHODS AND ANALYSIS This study will enroll patients with benign and low-grade brain tumours receiving partial brain radiotherapy. Patients will receive either hypofractionated (>2 Gy/fraction) or conventionally fractionated (1.8-2 Gy/fraction) RT. All participants will be followed for 12 months, with MRIs conducted pre-RT and 6-month and 12 month post-RT, along with a battery of neurocognitive tests and questionnaires. The study was initiated in late 2018 and will continue enrolling through 2024 with final follow-ups completing in 2025. The neurocognitive battery assesses visual and verbal memory, attention, executive function, processing speed and emotional cognition. MRI protocols incorporate diffusion tensor imaging and resting state fMRI to assess structural connectivity and functional connectivity, respectively. We will estimate the association between radiation dose, imaging metrics and cognitive outcomes. ETHICS AND DISSEMINATION This study has been approved by the Research Subjects Review Board at the University of Rochester (STUDY00001512: Cognitive changes in patients receiving partial brain radiation). All results will be published in peer-reviewed journals and at scientific conferences. TRIAL REGISTRATION NUMBER ClinicalTrials.gov NCT04390906.
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Affiliation(s)
- Sara J Hardy
- Department of Radiation Oncology, University of Rochester Medical Center, Rochester, New York, USA
- Department of Neurology, University of Rochester Medical Center, Rochester, New York, USA
| | - Alan J Finkelstein
- Department of Biomedical Engineering, University of Rochester, Rochester, New York, USA
- Center for Advanced Brain Imaging and Neurophysiology, University of Rochester Medical Center, Rochester, New York, USA
| | - Madalina Tivarus
- Center for Advanced Brain Imaging and Neurophysiology, University of Rochester Medical Center, Rochester, New York, USA
- Department of Imaging Sciences, University of Rochester Medical Center, Rochester, New York, USA
| | - Eva Culakova
- Department of Surgery, University of Rochester Medical Center, Rochester, New York, USA
| | - Nimish Mohile
- Department of Neurology, University of Rochester Medical Center, Rochester, New York, USA
| | - Miriam Weber
- Department of Neurology, University of Rochester Medical Center, Rochester, New York, USA
- Department of Obstetrics and Gynecology, University of Rochester Medical Center, Rochester, New York, USA
| | - Edward Lin
- Department of Imaging Sciences, University of Rochester Medical Center, Rochester, New York, USA
| | - Jianhui Zhong
- Department of Biomedical Engineering, University of Rochester, Rochester, New York, USA
- Center for Advanced Brain Imaging and Neurophysiology, University of Rochester Medical Center, Rochester, New York, USA
| | - Kenneth Usuki
- Department of Radiation Oncology, University of Rochester Medical Center, Rochester, New York, USA
| | - Giovanni Schifitto
- Department of Neurology, Department of Imaging Sciences, University of Rochester Medical Center, Rochester, New York, USA
| | - Michael Milano
- Department of Radiation Oncology, University of Rochester Medical Center, Rochester, New York, USA
| | - M C Janelsins-Benton
- Department of Radiation Oncology, University of Rochester Medical Center, Rochester, New York, USA
- Department of Surgery, University of Rochester Medical Center, Rochester, New York, USA
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Chu X, Gong J, Yang X, Ni J, Gu Y, Zhu Z. A "Seed-and-Soil" Radiomics Model Predicts Brain Metastasis Development in Lung Cancer: Implications for Risk-Stratified Prophylactic Cranial Irradiation. Cancers (Basel) 2023; 15:307. [PMID: 36612303 PMCID: PMC9818608 DOI: 10.3390/cancers15010307] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2022] [Revised: 12/26/2022] [Accepted: 12/28/2022] [Indexed: 01/09/2023] Open
Abstract
Introduction: Brain is a major site of metastasis for lung cancer, and effective therapy for developed brain metastasis (BM) is limited. Prophylactic cranial irradiation (PCI) has been shown to reduce BM rate and improve survival in small cell lung cancer, but this result was not replicated in unselected non-small cell lung cancer (NSCLC) and had the risk of inducing neurocognitive dysfunctions. We aimed to develop a radiomics BM prediction model for BM risk stratification in NSCLC patients. Methods: 256 NSCLC patients with no BM at baseline brain magnetic resonance imaging (MRI) were selected; 128 patients developed BM within three years after diagnosis and 128 remained BM-free. For radiomics analysis, both the BM and non-BM groups were randomly distributed into training and testing datasets at an 70%:30% ratio. Both brain MRI (representing the soil) and chest computed tomography (CT, representing the seed) radiomic features were extracted to develop the BM prediction models. We first developed the radiomic models using the training dataset (89 non-BM and 90 BM cases) and subsequently validated the models in the testing dataset (39 non-BM and 38 BM cases). A radiomics BM score (RadBM score) was generated, and BM-free survival were compared between RadBM score-high and RadBM score-low groups. Results: The radiomics model developed from baseline brain MRI features alone can predict BM development in NSCLC patients. A fusion model integrating brain MRI features with primary tumor CT features (seed-and-soil model) provided synergetic effect and was more efficient in predicting BM (areas under the receiver operating characteristic curve 0.84 (95% confidence interval: 0.80−0.89) and 0.80 (95% confidence interval: 0.71−0.88) in the training and testing datasets, respectively). BM-free survival was significantly shorter in the RadBM score-high group versus the RadBM score-low group (Log-rank, p < 0.001). Hazard ratios for BM were 1.056 (95% confidence interval: 1.044−1.068) per 0.01 increment in RadBM score. Cumulative BM rates at three years were 75.8% and 24.2% for the RadBM score-high and RadBM score-low groups, respectively. Only 1.2% (7/565) of the BM lesions were located within the hippocampal avoidance region. Conclusion: The results demonstrated that intrinsic features of a non-metastatic brain exert a significant impact on BM development, which is first-in-class in metastasis prediction studies. A radiomics BM prediction model utilizing both primary tumor and pre-metastatic brain features might provide a useful tool for individualized PCI administration in NSCLC patients more prone to develop BM.
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Affiliation(s)
- Xiao Chu
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
- Shanghai Clinical Research Center for Radiation Oncology, Shanghai 200032, China
- Shanghai Key Laboratory of Radiation Oncology, Shanghai 200032, China
| | - Jing Gong
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
- Department of Radiology, Fudan University Shanghai Cancer Center, Shanghai 200032, China
| | - Xi Yang
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
- Shanghai Clinical Research Center for Radiation Oncology, Shanghai 200032, China
- Shanghai Key Laboratory of Radiation Oncology, Shanghai 200032, China
| | - Jianjiao Ni
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
- Shanghai Clinical Research Center for Radiation Oncology, Shanghai 200032, China
- Shanghai Key Laboratory of Radiation Oncology, Shanghai 200032, China
| | - Yajia Gu
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
- Department of Radiology, Fudan University Shanghai Cancer Center, Shanghai 200032, China
| | - Zhengfei Zhu
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
- Shanghai Clinical Research Center for Radiation Oncology, Shanghai 200032, China
- Shanghai Key Laboratory of Radiation Oncology, Shanghai 200032, China
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Xue J, Jin S, Zhang H, Zou K, Sheng J, Tang J, Zhao W, Yang P, Tang L, Lv X, Lv L. A simplified non-coplanar volumetric modulated arc therapy for the whole brain radiotherapy with hippocampus avoidance. Front Oncol 2023; 13:1143564. [PMID: 37152035 PMCID: PMC10155751 DOI: 10.3389/fonc.2023.1143564] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2023] [Accepted: 03/24/2023] [Indexed: 05/09/2023] Open
Abstract
Purpose To evaluate the feasibility of using a simplified non-coplanar volumetric modulated arc therapy (NC-VMAT) and investigate its dosimetric advantages compared with intensity modulated radiation therapy (IMRT) and coplanar volumetric modulated arc therapy (C-VMAT) for hippocampal-avoidance whole brain radiation therapy (HA-WBRT). Methods Ten patients with brain metastase (BM) were included for HA-WBRT. Three treatment plans were generated for each case using IMRT, C-VMAT, and NC-VMAT, respectively. Results The dosimetric results of the three techniques complied roughly with the RTOG 0933 criteria. After dose normalization, the V30Gy of whole brain planned target volume (WB-PTV) in all the plans was controlled at 95%. Homogeneity index (HI) of WB-PTV was significantly reduced in NC-VMAT (0.249 ± 0.017) over IMRT (0.265 ± 0.020, p=0.005) and C-VMAT (0.261 ± 0.014, p=0.020). In terms of conformity index (CI), NC-VMAT could provide a value of 0.821 ± 0.010, which was significantly superior to IMRT (0.788 ± 0.019, p<0.001). According to D2% of WB-PTV, NC-VMAT could provide a value of 35.62 ± 0.37Gy, significantly superior to IMRT (36.43 ± 0.65Gy, p<0.001). According to D50% of WB-PTV, NC-VMAT can achieve the lowest value of 33.18 ± 0.29Gy, significantly different from IMRT (33.47 ± 0.43, p=0.034) and C-VMAT (33.58 ± 0.37, p=0.006). Regarding D2%, D98%, and Dmean of hippocampus, NC-VMAT could control them at 15.57 ± 0.18Gy, 8.37 ± 0.26Gy and 11.71 ± 0.48Gy, respectively. D2% and Dmean of hippocampus for NC-VMAT was significantly lower than IMRT (D2%: 16.07 ± 0.29Gy, p=0.001 Dmean: 12.18 ± 0.33Gy, p<0.001) and C-VMAT (D2%: 15.92 ± 0.37Gy, p=0.009 Dmean: 12.21 ± 0.54Gy, p<0.001). For other organs-at-risk (OARs), according to D2% of the right optic nerves and the right lenses, NC-VMAT had the lowest values of 31.86 ± 1.11Gy and 7.15 ± 0.31Gy, respectively, which were statistically different from the other two techniques. For other organs including eyes and optic chiasm, NC-VMAT could achieve the lowest doses, different from IMRT statistically. Conclusion The dosimetry of the three techniques for HA-WBRT could roughly comply with the proposals from RTOG 0933. After dose normalization (D95%=30Gy), NC-VMAT could significantly improve dose homogeneity and reduce the D50% in the brain. Besides, it can reduce the D2% of the hippocampus, optic nerves, and lens. With this approach, an efficient and straightforward plan was accomplished.
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Affiliation(s)
- Juan Xue
- The Department of Radiation Oncology, First Affiliated Hospital, Dalian Medical University, Dalian, Liaoning, China
| | - Sunian Jin
- The Department of Radiation Oncology, First Affiliated Hospital, Dalian Medical University, Dalian, Liaoning, China
| | - Hongtao Zhang
- The Department of Radiation Oncology, First Affiliated Hospital, Dalian Medical University, Dalian, Liaoning, China
| | - Kun Zou
- The Department of Radiation Oncology, First Affiliated Hospital, Dalian Medical University, Dalian, Liaoning, China
| | - Junxiu Sheng
- The Department of Radiation Oncology, First Affiliated Hospital, Dalian Medical University, Dalian, Liaoning, China
| | - Jinhai Tang
- The Department of Radiation Oncology, First Affiliated Hospital, Dalian Medical University, Dalian, Liaoning, China
| | - Wanying Zhao
- The Department of Radiation Oncology, First Affiliated Hospital, Dalian Medical University, Dalian, Liaoning, China
| | - Ping Yang
- The Department of Radiation Oncology, First Affiliated Hospital, Dalian Medical University, Dalian, Liaoning, China
| | - Lufan Tang
- The Department of Radiation Oncology, First Affiliated Hospital, Dalian Medical University, Dalian, Liaoning, China
| | - Xiupeng Lv
- The Department of Radiation Oncology, First Affiliated Hospital, Dalian Medical University, Dalian, Liaoning, China
- *Correspondence: Xiupeng Lv, ; Li Lv,
| | - Li Lv
- The Department of Pathology, Second Affiliated Hospital, Dalian Medical University, Dalian, Liaoning, China
- *Correspondence: Xiupeng Lv, ; Li Lv,
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Yang F, Dinakaran D, Heikal AA, Yaghoobpour Tari S, Ghosh S, Amanie J, Murtha A, Rowe LS, Roa WH, Patel S. Dosimetric predictors of toxicity in a randomized study of short-course vs conventional radiotherapy for glioblastoma. Radiother Oncol 2022; 177:152-157. [PMID: 36273738 DOI: 10.1016/j.radonc.2022.10.016] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Revised: 09/12/2022] [Accepted: 10/14/2022] [Indexed: 11/13/2022]
Abstract
PURPOSE There is no consensus on appropriate organ at risk (OAR) constraints for short-course radiotherapy for patients with glioblastoma. Using dosimetry and prospectively-collected toxicity data from a trial of short-course radiotherapy for glioblastoma, this study aims to empirically examine the OAR constraints, with particular attention to left hippocampus dosimetry and impact on neuro-cognitive decline. METHODS AND MATERIALS Data was taken from a randomized control trial of 133 adults (age 18-70 years; ECOG performance score 0-2) with newly diagnosed glioblastoma treated with 60 Gy in 30 (conventional arm) versus 20 (short-course arm) fractions of adjuvant chemoradiotherapy (ClinicalTrials.gov Identifier: NCT02206230). The delivered plan's dosimetry to the OARs was correlated to prospective-collected toxicity and Mini-Mental State Examination (MMSE) data. RESULTS Toxicity events were not significantly increased in the short-course arm versus the conventional arm. Across all OARs, delivered radiation doses within protocol-allowable maximum doses correlated with lack of grade ≥ 2 toxicities in both arms (p < 0.001), while patients with OAR doses at or above protocol limits correlated with increased grade ≥ 2 toxicities across all examined OARs in both arms (p-values 0.063-0.250). Mean left hippocampus dose was significantly associated with post-radiotherapy decline in MMSE scores (p = 0.005), while the right hippocampus mean dose did not reach statistical significance (p = 0.277). Compared to the original clinical plan, RapidPlan left hippocampus sparing model decreased left hippocampus mean dose by 43 % (p < 0.001), without compromising planning target volume coverage. CONCLUSIONS In this trial, protocol OAR constraints were appropriate for limiting grade ≥ 2 toxicities in conventional and short-course adjuvant chemoradiotherapy for glioblastoma. Higher left hippocampal mean doses were predictive for neuro-cognitive decline post-radiotherapy. Routine contouring and use of dose constraints to limit hippocampal dose is recommended to minimize neuro-cognitive decline in patients with glioblastoma treated with chemoradiotherapy.
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Affiliation(s)
- Fan Yang
- Division of Radiation Oncology, University of Alberta, Cross Cancer Institute, Edmonton, Alberta, Canada
| | - Deepak Dinakaran
- Division of Radiation Oncology, University of Alberta, Cross Cancer Institute, Edmonton, Alberta, Canada
| | - Amr A Heikal
- Division of Medical Physics, University of Alberta, Cross Cancer Institute, Edmonton, Alberta, Canada
| | - Shima Yaghoobpour Tari
- Division of Medical Physics, University of Alberta, Cross Cancer Institute, Edmonton, Alberta, Canada
| | - Sunita Ghosh
- Division of Medical Oncology, University of Alberta, Cross Cancer Institute, Edmonton, Alberta, Canada
| | - John Amanie
- Division of Radiation Oncology, University of Alberta, Cross Cancer Institute, Edmonton, Alberta, Canada
| | - Albert Murtha
- Division of Radiation Oncology, University of Alberta, Cross Cancer Institute, Edmonton, Alberta, Canada
| | - Lindsay S Rowe
- Division of Radiation Oncology, University of Alberta, Cross Cancer Institute, Edmonton, Alberta, Canada
| | - Wilson H Roa
- Division of Radiation Oncology, University of Alberta, Cross Cancer Institute, Edmonton, Alberta, Canada
| | - Samir Patel
- Division of Radiation Oncology, University of Alberta, Cross Cancer Institute, Edmonton, Alberta, Canada.
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Aizer AA, Lamba N, Ahluwalia MS, Aldape K, Boire A, Brastianos PK, Brown PD, Camidge DR, Chiang VL, Davies MA, Hu LS, Huang RY, Kaufmann T, Kumthekar P, Lam K, Lee EQ, Lin NU, Mehta M, Parsons M, Reardon DA, Sheehan J, Soffietti R, Tawbi H, Weller M, Wen PY. Brain metastases: A Society for Neuro-Oncology (SNO) consensus review on current management and future directions. Neuro Oncol 2022; 24:1613-1646. [PMID: 35762249 PMCID: PMC9527527 DOI: 10.1093/neuonc/noac118] [Citation(s) in RCA: 74] [Impact Index Per Article: 24.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023] Open
Abstract
Brain metastases occur commonly in patients with advanced solid malignancies. Yet, less is known about brain metastases than cancer-related entities of similar incidence. Advances in oncologic care have heightened the importance of intracranial management. Here, in this consensus review supported by the Society for Neuro-Oncology (SNO), we review the landscape of brain metastases with particular attention to management approaches and ongoing efforts with potential to shape future paradigms of care. Each coauthor carried an area of expertise within the field of brain metastases and initially composed, edited, or reviewed their specific subsection of interest. After each subsection was accordingly written, multiple drafts of the manuscript were circulated to the entire list of authors for group discussion and feedback. The hope is that the these consensus guidelines will accelerate progress in the understanding and management of patients with brain metastases, and highlight key areas in need of further exploration that will lead to dedicated trials and other research investigations designed to advance the field.
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Affiliation(s)
- Ayal A Aizer
- Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women’s Hospital, Boston, Massachusetts, USA
| | - Nayan Lamba
- Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women’s Hospital, Boston, Massachusetts, USA
- Harvard Radiation Oncology Program, Boston, Massachusetts, USA
| | | | - Kenneth Aldape
- Laboratory of Pathology, National Cancer Institute, Bethesda, Maryland, USA
| | - Adrienne Boire
- Department of Neurology, Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - Priscilla K Brastianos
- Departments of Neuro-Oncology and Medical Oncology, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Paul D Brown
- Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota, USA
| | - D Ross Camidge
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
| | - Veronica L Chiang
- Departments of Neurosurgery and Radiation Oncology, Yale School of Medicine, New Haven, Connecticut, USA
| | - Michael A Davies
- Department of Melanoma Medical Oncology, MD Anderson Cancer Center, Houston, Texas, USA
| | - Leland S Hu
- Department of Radiology, Neuroradiology Division, Mayo Clinic, Phoenix, Arizona, USA
| | - Raymond Y Huang
- Department of Radiology, Brigham and Women’s Hospital, Boston, Massachusetts, USA
| | | | - Priya Kumthekar
- Department of Neurology at The Feinberg School of Medicine at Northwestern University and The Malnati Brain Tumor Institute at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois, USA
| | - Keng Lam
- Department of Neurology, Kaiser Permanente, Los Angeles Medical Center, Los Angeles, California, USA
| | - Eudocia Q Lee
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
| | - Nancy U Lin
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
| | - Minesh Mehta
- Department of Radiation Oncology, Miami Cancer Institute, Miami, Florida, USA
| | - Michael Parsons
- Departments of Oncology and Psychiatry, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - David A Reardon
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
| | - Jason Sheehan
- Department of Neurosurgery, University of Virginia, Charlottesville, Virginia, USA
| | - Riccardo Soffietti
- Division of Neuro-Oncology, Department of Neuroscience Rita Levi Montalcini, University of Turin, Turin, Italy
| | - Hussein Tawbi
- Department of Melanoma Medical Oncology, MD Anderson Cancer Center, Houston, Texas, USA
| | - Michael Weller
- Department of Neurology, University Hospital and University of Zurich, Zurich, Switzerland
| | - Patrick Y Wen
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
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50
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Kim JS, Kim K, Jung W, Shin KH, Im SA, Kim HJ, Kim YB, Chang JS, Kim JH, Choi DH, Park YH, Kim DY, Kim TH, Choi BO, Lee SW, Kim S, Kwon J, Kang KM, Chung WK, Kim KS, Nam JH, Yoon WS, Kim JH, Cha J, Oh YK, Kim IA. The Pattern of Care for Brain Metastasis from Breast Cancer over the Past 10 Years in Korea: A Multicenter Retrospective Study (KROG 16-12). Cancer Res Treat 2022; 54:1121-1129. [PMID: 34990524 PMCID: PMC9582469 DOI: 10.4143/crt.2021.1083] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2021] [Accepted: 12/30/2021] [Indexed: 11/30/2022] Open
Abstract
PURPOSE We aimed to investigate manifestations and patterns of care for patients with brain metastasis (BM) from breast cancer (BC) and compared their overall survival (OS) from 2005 through 2014 in Korea. MATERIALS AND METHODS We retrospectively reviewed 600 BC patients with BM diagnosed between 2005 and 2014. The median follow-up duration was 12.5 months. We categorized the patients into three groups according to the year when BM was initially diagnosed (group I [2005-2008], 98 patients; group II [2009-2011], 200 patients; and group III [2012-2014], 302 patients). RESULTS Over time, the median age at BM diagnosis increased by 2.2 years (group I, 49.0 years; group II, 48.3 years; and group III, 51.2 years; p=0.008). The percentage of patients with extracranial metastasis was 73.5%, 83.5%, and 86.4% for group I, II, and III, respectively (p=0.011). The time interval between BC and BM was prolonged in patients with stage III primary BC (median, 2.4 to 3 years; p=0.029). As an initial brain-directed treatment, whole-brain radiotherapy alone decreased from 80.0% in 2005 to 41.1% in 2014. Meanwhile, stereotactic radiosurgery or fractionated stereotactic radiotherapy alone increased from 13.3% to 34.7% during the same period (p=0.005). The median OS for group I, II, and III was 15.6, 17.9, and 15.0 months, respectively, with no statistical significance. CONCLUSION The manifestations of BM from BC and the pattern of care have changed from 2005 to 2014 in Korea. However, the OS has remained relatively unchanged over the 10 years.
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Affiliation(s)
- Jae Sik Kim
- Department of Radiation Oncology, Seoul National University College of Medicine, Seoul,
Korea
| | - Kyubo Kim
- Department of Radiation Oncology, Ewha Womans University College of Medicine, Seoul,
Korea
| | - Wonguen Jung
- Department of Radiation Oncology, Ewha Womans University College of Medicine, Seoul,
Korea
| | - Kyung Hwan Shin
- Department of Radiation Oncology, Seoul National University College of Medicine, Seoul,
Korea
| | - Seock-Ah Im
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul,
Korea
| | - Hee-Jun Kim
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul,
Korea
| | - Yong Bae Kim
- Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul,
Korea
| | - Jee Suk Chang
- Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul,
Korea
| | - Jee Hyun Kim
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul,
Korea
| | - Doo Ho Choi
- Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul,
Korea
| | - Yeon Hee Park
- Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul,
Korea
| | - Dae Yong Kim
- Proton Therapy Center, National Cancer Center, Goyang,
Korea
| | - Tae Hyun Kim
- Proton Therapy Center, National Cancer Center, Goyang,
Korea
| | - Byung Ock Choi
- Department of Radiation Oncology, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul,
Korea
| | - Sea-Won Lee
- Department of Radiation Oncology, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul,
Korea
- Department of Radiation Oncology, Eunpyeong St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul,
Korea
| | - Suzy Kim
- Department of Radiation Oncology, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul,
Korea
| | - Jeanny Kwon
- Department of Radiation Oncology, Chungnam National University College of Medicine, Daejeon,
Korea
| | - Ki Mun Kang
- Department of Radiation Oncology, Gyeongsang National University School of Medicine and Gyeongsang National University Changwon Hospital, Changwon,
Korea
| | - Woong-Ki Chung
- Department of Radiation Oncology, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Hwasun,
Korea
| | - Kyung Su Kim
- Department of Radiation Oncology, Ewha Womans University College of Medicine, Seoul,
Korea
- Department of Radiation Oncology, Dongnam Institute of Radiological and Medical Sciences, Busan,
Korea
| | - Ji Ho Nam
- Department of Radiation Oncology, Yangsan Pusan National University Hospital, Pusan National University School of Medicine, Yangsan,
Korea
| | - Won Sup Yoon
- Department of Radiation Oncology, Korea University Ansan Hospital, Korea University College of Medicine, Asan,
Korea
| | - Jin Hee Kim
- Department of Radiation Oncology, Keimyung University Dongsan Medical Center, Keimyung University School of Medicine, Daegu,
Korea
| | - Jihye Cha
- Department of Radiation Oncology, Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, Wonju,
Korea
| | - Yoon Kyeong Oh
- Department of Radiation Oncology, Chosun University Medical School, Gwangju,
Korea
| | - In Ah Kim
- Department of Radiation Oncology, Seoul National University College of Medicine, Seoul,
Korea
- Department of Radiation Oncology, Seoul National University Bundang Hospital, Seongnam,
Korea
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