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Zhong C, Huang M, Yu H, Yuan J, Xie R, Lai Z, Niu S, Tang C. Sequential or simultaneous-integrated boost in early-stage breast cancer patients: trade-offs between skin toxicity and risk of compromised coverage. Radiat Oncol 2025; 20:10. [PMID: 39833842 PMCID: PMC11744842 DOI: 10.1186/s13014-025-02584-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2024] [Accepted: 01/08/2025] [Indexed: 01/22/2025] Open
Abstract
PURPOSE To determine the dosimetric effects of set-up errors on boost coverage, and compares skin toxicity of sequential and simultaneous boost techniques for left-sided breast cancer. MATERIALS AND METHODS This retrospective study included 23 early-stage breast cancer cases. Single isocenter HFWBI-SIB(s-SIB), single isocenter HFWBI-SB(s-SB) and dual isocenter HFWBI-SB(d-SB) were planing. Rotations of 0.5°, 1°, and 2° coupled with translationals of 0.5 mm, 1.0 mm, and 2.0 mm were applied along three orthogonal axes. The dose to 95% of the PTV (D95) and the volume covered by 95% of the prescribed dose (V95) were evaluated using GEE univariate analysis to determine how PTV coverage was related to 1/CIRTOG, PTVboost volume, PTVboost separation to isocenter. The relationship between the high-dose regions within the PTVbreast and Ratio_V was evaluated using univariate analysis. RESULTS The s-SIB had optimal target coverage and lower high-dose volume, but it increased the risk of compromised coverage to tumor bed. For the s-SB technique, V95 exceeded 95% under all setup errors. At 2.0° coupled with 2.0 mm, s-SIB and d-SB exhibited V95 values below 95% in 34.8% and 8.7% of cases, respectively. At other setup errors, both s-SIB and d-SB demonstrated V95 values greater than 95%. Notably, high-dose regions such as V105%, V107%, and V110% within the PTVbreast across the three techniques displayed a significant correlation with Ratio_V. CONCLUSION Simultaneous-integrated boost for early-stage breast cancer can reduce skin toxicity compared to sequential techniques but with the risk of compromising tumor bed coverage.
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Affiliation(s)
- Changyou Zhong
- Radiotherapy Department, Meizhou People's Hospital, Huangtang Hospital, Meizhou, China
| | - Minfeng Huang
- Department of Oncology, First Affiliated Hospital of Gannan Medical University, Ganzhou, China
- First Clinical Medical College, Gannan Medical University, Ganzhou, China
- Jiangxi Clinical Research Center for Cancer, Ganzhou, China
| | - Haidong Yu
- Radiotherapy Department, Meizhou People's Hospital, Huangtang Hospital, Meizhou, China
| | - Jun Yuan
- Department of Oncology, First Affiliated Hospital of Gannan Medical University, Ganzhou, China
- First Clinical Medical College, Gannan Medical University, Ganzhou, China
- Jiangxi Clinical Research Center for Cancer, Ganzhou, China
| | - Ruilian Xie
- Department of Oncology, First Affiliated Hospital of Gannan Medical University, Ganzhou, China
- First Clinical Medical College, Gannan Medical University, Ganzhou, China
- Jiangxi Clinical Research Center for Cancer, Ganzhou, China
| | - Zhenzhen Lai
- School of Mathematics and Computer Science, Gannan Normal University, Ganzhou, China
| | - Shanzhou Niu
- School of Mathematics and Computer Science, Gannan Normal University, Ganzhou, China.
- Ganzhou Key Laboratory of Computational Imaging, Gannan Normal University, Ganzhou, China.
| | - Chunbo Tang
- Department of Oncology, First Affiliated Hospital of Gannan Medical University, Ganzhou, China.
- First Clinical Medical College, Gannan Medical University, Ganzhou, China.
- Jiangxi Clinical Research Center for Cancer, Ganzhou, China.
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Saldarriaga Vargas C, Andersson M, Bouvier-Capely C, Li WB, Madas B, Covens P, Struelens L, Strigari L. Heterogeneity of absorbed dose distribution in kidney tissues and dose-response modelling of nephrotoxicity in radiopharmaceutical therapy with beta-particle emitters: A review. Z Med Phys 2024; 34:491-509. [PMID: 37031068 PMCID: PMC11624361 DOI: 10.1016/j.zemedi.2023.02.006] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2022] [Revised: 02/20/2023] [Accepted: 02/27/2023] [Indexed: 04/08/2023]
Abstract
Absorbed dose heterogeneity in kidney tissues is an important issue in radiopharmaceutical therapy. The effect of absorbed dose heterogeneity in nephrotoxicity is, however, not fully understood yet, which hampers the implementation of treatment optimization by obscuring the interpretation of clinical response data and the selection of optimal treatment options. Although some dosimetry methods have been developed for kidney dosimetry to the level of microscopic renal substructures, the clinical assessment of the microscopic distribution of radiopharmaceuticals in kidney tissues currently remains a challenge. This restricts the anatomical resolution of clinical dosimetry, which hinders a thorough clinical investigation of the impact of absorbed dose heterogeneity. The potential of absorbed dose-response modelling to support individual treatment optimization in radiopharmaceutical therapy is recognized and gaining attraction. However, biophysical modelling is currently underexplored for the kidney, where particular modelling challenges arise from the convolution of a complex functional organization of renal tissues with the function-mediated dose distribution of radiopharmaceuticals. This article reviews and discusses the heterogeneity of absorbed dose distribution in kidney tissues and the absorbed dose-response modelling of nephrotoxicity in radiopharmaceutical therapy. The review focuses mainly on the peptide receptor radionuclide therapy with beta-particle emitting somatostatin analogues, for which the scientific literature reflects over two decades of clinical experience. Additionally, detailed research perspectives are proposed to address various identified challenges to progress in this field.
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Affiliation(s)
- Clarita Saldarriaga Vargas
- Radiation Protection Dosimetry and Calibrations, Belgian Nuclear Research Centre (SCK CEN), Mol, Belgium; In Vivo Cellular and Molecular Imaging Laboratory, Vrije Universiteit Brussel, Brussels, Belgium.
| | - Michelle Andersson
- Radiation Protection Dosimetry and Calibrations, Belgian Nuclear Research Centre (SCK CEN), Mol, Belgium; Medical Physics Department, Jules Bordet Institute, Université Libre de Bruxelles, Brussels, Belgium
| | - Céline Bouvier-Capely
- Institut de Radioprotection et Sûreté Nucléaire (IRSN), PSE-SANTE/SESANE/LRSI, Fontenay-aux-Roses, France
| | - Wei Bo Li
- Institute of Radiation Medicine, Helmholtz Zentrum München - German Research Center for Environmental Health (GmbH), Neuherberg, Germany
| | - Balázs Madas
- Environmental Physics Department, Centre for Energy Research, Budapest, Hungary
| | - Peter Covens
- In Vivo Cellular and Molecular Imaging Laboratory, Vrije Universiteit Brussel, Brussels, Belgium
| | - Lara Struelens
- Radiation Protection Dosimetry and Calibrations, Belgian Nuclear Research Centre (SCK CEN), Mol, Belgium
| | - Lidia Strigari
- Department of Medical Physics, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
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Cao T, Yuan Q, Dai Z. A new formula for calculating normal tissue complication probability. PRECISION RADIATION ONCOLOGY 2024; 8:126-131. [PMID: 40336978 PMCID: PMC11935045 DOI: 10.1002/pro6.1240] [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: 05/07/2024] [Revised: 08/16/2024] [Accepted: 09/03/2024] [Indexed: 05/09/2025] Open
Abstract
Purpose To facilitate the use of quantitative modeling of biological effects in treatment planning by introducing a simpler function equivalent to the Lyman formula for calculating normal tissue complication probability (NTCP). Methods We first provide an approximation of the Lyman-Kutcher-Burman (LKB) formula using three parameters (n, m, TD50) as a function of equivalent uniform dose (EUD). The parameters for the new formula are defined in terms of the Lyman model's m and TD50. Conversely, m and TD50 are expressed in terms of the parameters of the new equation. The role of the Lyman volume-effect parameter n remains unchanged from its role in the Lyman model. Results The new formula, which exhibits a sigmoidal shape, demonstrates symmetry about TD50, akin to the LKB model. The difference in NTCP between the two formulas is less than 0.1%. The parameters (n, m, TD50) are preserved through rigorous mathematical deduction and have been recalibrated to the tolerance data of Emani et al. using the proposed formula. This new model provides a better fit to these data than the model by Burman et al., which was fitted "by eye" rather than using statistical methods. Conclusion We have developed a formula that represents NTCP as a function of EUD, which proves to be potentially useful. The parameters derived in this study are mathematically robust and offer a superior fit to the data compared to previous efforts. Additionally, the new model fits brain data as well as, if not better than, the LKB model.
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Affiliation(s)
- Tingting Cao
- Tongji HospitalTongji Medical College of Huazhong University of Science and TechnologyWuhanChina
| | - Qingqing Yuan
- Cancer Hospital Chinese Academy of Medical SciencesShenzhen CenterShenzhenChina
| | - Zhitao Dai
- Cancer Hospital Chinese Academy of Medical SciencesShenzhen CenterShenzhenChina
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Besuglow J, Tessonnier T, Mein S, Eichkorn T, Haberer T, Herfarth K, Abdollahi A, Debus J, Mairani A. Understanding Relative Biological Effectiveness and Clinical Outcome of Prostate Cancer Therapy Using Particle Irradiation: Analysis of Tumor Control Probability With the Modified Microdosimetric Kinetic Model. Int J Radiat Oncol Biol Phys 2024; 119:1545-1556. [PMID: 38423224 DOI: 10.1016/j.ijrobp.2024.02.025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2023] [Revised: 12/22/2023] [Accepted: 02/10/2024] [Indexed: 03/02/2024]
Abstract
PURPOSE Recent experimental studies and clinical trial results might indicate that-at least for some indications-continued use of the mechanistic model for relative biological effectiveness (RBE) applied at carbon ion therapy facilities in Europe for several decades (LEM-I) may be unwarranted. We present a novel clinical framework for prostate cancer treatment planning and tumor control probability (TCP) prediction based on the modified microdosimetric kinetic model (mMKM) for particle therapy. METHODS AND MATERIALS Treatment plans of 91 patients with prostate tumors (proton: 46, carbon ions: 45) applying 66 GyRBE [RBE = 1.1 for protons and LEM-I, (α/β)x = 2.0 Gy, for carbon ions] in 20 fractions were recalculated using mMKM [(α/β)x = 3.1 Gy]). Based solely on the response data of photon-irradiated patient groups stratified according to risk and usage of androgen deprivation therapy, we derived parameters for an mMKM-based Poisson-TCP model. Subsequently, new carbon and helium ion plans, adhering to prescribed biological dose criteria, were generated. These were systematically compared with the clinical experience of Japanese centers employing an analogous fractionation scheme and existing proton plans. RESULTS mMKM predictions suggested significant biological dose deviation between the proton and carbon ion arms. Patients irradiated with protons received (3.25 ± 0.08) GyRBEmMKM/Fx, whereas patients treated with carbon ions received(2.51 ± 0.05) GyRBEmMKM/Fx. TCP predictions were (86 ± 3)% for protons and (52 ± 4)% for carbon ions, matching the clinical outcome of 85% and 50%. Newly optimized carbon ion plans, guided by the mMKM/TCP model, effectively replicated clinical data from Japanese centers. Using mMKM, helium ions exhibited similar target coverage as proton and carbon ions and improved rectum and bladder sparing compared with proton. CONCLUSIONS Our mMKM-based model for prostate cancer treatment planning and TCP prediction was validated against clinical data for proton and carbon ion therapy, and its application was extended to helium ion therapy. Based on the data presented in this work, mMKM seems to be a good candidate for clinical biological calculations in carbon ion therapy for prostate cancer.
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Affiliation(s)
- Judith Besuglow
- Clinical Cooperation Unit Translational Radiation Oncology (E210), National Center for Tumor Diseases (NCT), Heidelberg University Hospital (UKHD) and German Cancer Research Center (DKFZ), Heidelberg, Germany; Division of Molecular and Translational Radiation Oncology, Department of Radiation Oncology, Heidelberg Faculty of Medicine (MFHD) and Heidelberg University Hospital (UKHD), Heidelberg Ion-Beam Therapy Center (HIT), Heidelberg, Germany; German Cancer Consortium (DKTK) Core-Center Heidelberg, German Cancer Research Center (DKFZ), Heidelberg, Germany; National Center for Radiation Oncology (NCRO), Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg University and German Cancer Research Center (DKFZ), Heidelberg, Germany; Department of Physics and Astronomy, Heidelberg University, Heidelberg, Germany
| | - Thomas Tessonnier
- Clinical Cooperation Unit Translational Radiation Oncology (E210), National Center for Tumor Diseases (NCT), Heidelberg University Hospital (UKHD) and German Cancer Research Center (DKFZ), Heidelberg, Germany; Heidelberg Ion-Beam Therapy Center (HIT), Heidelberg, Germany
| | - Stewart Mein
- Clinical Cooperation Unit Translational Radiation Oncology (E210), National Center for Tumor Diseases (NCT), Heidelberg University Hospital (UKHD) and German Cancer Research Center (DKFZ), Heidelberg, Germany; Division of Molecular and Translational Radiation Oncology, Department of Radiation Oncology, Heidelberg Faculty of Medicine (MFHD) and Heidelberg University Hospital (UKHD), Heidelberg Ion-Beam Therapy Center (HIT), Heidelberg, Germany; German Cancer Consortium (DKTK) Core-Center Heidelberg, German Cancer Research Center (DKFZ), Heidelberg, Germany; National Center for Radiation Oncology (NCRO), Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg University and German Cancer Research Center (DKFZ), Heidelberg, Germany; Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Tanja Eichkorn
- National Center for Radiation Oncology (NCRO), Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg University and German Cancer Research Center (DKFZ), Heidelberg, Germany; Heidelberg Ion-Beam Therapy Center (HIT), Heidelberg, Germany; Department of Radiation Oncology, Heidelberg University Hospital (UKHD), Heidelberg, Germany; National Center for Tumor Diseases (NCT), Heidelberg, Germany
| | - Thomas Haberer
- National Center for Radiation Oncology (NCRO), Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg University and German Cancer Research Center (DKFZ), Heidelberg, Germany; Heidelberg Ion-Beam Therapy Center (HIT), Heidelberg, Germany
| | - Klaus Herfarth
- National Center for Radiation Oncology (NCRO), Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg University and German Cancer Research Center (DKFZ), Heidelberg, Germany; Heidelberg Ion-Beam Therapy Center (HIT), Heidelberg, Germany; Department of Radiation Oncology, Heidelberg University Hospital (UKHD), Heidelberg, Germany; National Center for Tumor Diseases (NCT), Heidelberg, Germany
| | - Amir Abdollahi
- Clinical Cooperation Unit Translational Radiation Oncology (E210), National Center for Tumor Diseases (NCT), Heidelberg University Hospital (UKHD) and German Cancer Research Center (DKFZ), Heidelberg, Germany; Division of Molecular and Translational Radiation Oncology, Department of Radiation Oncology, Heidelberg Faculty of Medicine (MFHD) and Heidelberg University Hospital (UKHD), Heidelberg Ion-Beam Therapy Center (HIT), Heidelberg, Germany; German Cancer Consortium (DKTK) Core-Center Heidelberg, German Cancer Research Center (DKFZ), Heidelberg, Germany; National Center for Radiation Oncology (NCRO), Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg University and German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Jürgen Debus
- German Cancer Consortium (DKTK) Core-Center Heidelberg, German Cancer Research Center (DKFZ), Heidelberg, Germany; National Center for Radiation Oncology (NCRO), Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg University and German Cancer Research Center (DKFZ), Heidelberg, Germany; Heidelberg Ion-Beam Therapy Center (HIT), Heidelberg, Germany; Department of Radiation Oncology, Heidelberg University Hospital (UKHD), Heidelberg, Germany; National Center for Tumor Diseases (NCT), Heidelberg, Germany; Clinical Cooperation Unit Radiation Oncology (E050), German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Andrea Mairani
- Clinical Cooperation Unit Translational Radiation Oncology (E210), National Center for Tumor Diseases (NCT), Heidelberg University Hospital (UKHD) and German Cancer Research Center (DKFZ), Heidelberg, Germany; Heidelberg Ion-Beam Therapy Center (HIT), Heidelberg, Germany; Medical Physics, National Centre of Oncological Hadrontherapy (CNAO), Pavia, Italy.
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5
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Chen ZJ, Li XA, Brenner DJ, Hellebust TP, Hoskin P, Joiner MC, Kirisits C, Nath R, Rivard MJ, Thomadsen BR, Zaider M. AAPM Task Group Report 267: A joint AAPM GEC-ESTRO report on biophysical models and tools for the planning and evaluation of brachytherapy. Med Phys 2024; 51:3850-3923. [PMID: 38721942 DOI: 10.1002/mp.17062] [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: 12/05/2023] [Revised: 02/28/2024] [Accepted: 03/08/2024] [Indexed: 06/05/2024] Open
Abstract
Brachytherapy utilizes a multitude of radioactive sources and treatment techniques that often exhibit widely different spatial and temporal dose delivery patterns. Biophysical models, capable of modeling the key interacting effects of dose delivery patterns with the underlying cellular processes of the irradiated tissues, can be a potentially useful tool for elucidating the radiobiological effects of complex brachytherapy dose delivery patterns and for comparing their relative clinical effectiveness. While the biophysical models have been used largely in research settings by experts, it has also been used increasingly by clinical medical physicists over the last two decades. A good understanding of the potentials and limitations of the biophysical models and their intended use is critically important in the widespread use of these models. To facilitate meaningful and consistent use of biophysical models in brachytherapy, Task Group 267 (TG-267) was formed jointly with the American Association of Physics in Medicine (AAPM) and The Groupe Européen de Curiethérapie and the European Society for Radiotherapy & Oncology (GEC-ESTRO) to review the existing biophysical models, model parameters, and their use in selected brachytherapy modalities and to develop practice guidelines for clinical medical physicists regarding the selection, use, and interpretation of biophysical models. The report provides an overview of the clinical background and the rationale for the development of biophysical models in radiation oncology and, particularly, in brachytherapy; a summary of the results of literature review of the existing biophysical models that have been used in brachytherapy; a focused discussion of the applications of relevant biophysical models for five selected brachytherapy modalities; and the task group recommendations on the use, reporting, and implementation of biophysical models for brachytherapy treatment planning and evaluation. The report concludes with discussions on the challenges and opportunities in using biophysical models for brachytherapy and with an outlook for future developments.
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Affiliation(s)
- Zhe Jay Chen
- Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, Connecticut, USA
| | - X Allen Li
- Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
| | - David J Brenner
- Center for Radiological Research, Columbia University Medical Center, New York, New York, USA
| | - Taran P Hellebust
- Department of Oncology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway
| | - Peter Hoskin
- Mount Vernon Cancer Center, Mount Vernon Hospital, Northwood, UK
- University of Manchester, Manchester, UK
| | - Michael C Joiner
- Department of Radiation Oncology, Wayne State University School of Medicine, Detroit, Michigan, USA
| | - Christian Kirisits
- Department of Radiation Oncology, Medical University of Vienna, Vienna, Austria
| | - Ravinder Nath
- Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, Connecticut, USA
| | - Mark J Rivard
- Department of Radiation Oncology, Brown University School of Medicine, Providence, Rhode Island, USA
| | - Bruce R Thomadsen
- Department of Medical Physics, University of Wisconsin, Madison, Wisconsin, USA
| | - Marco Zaider
- Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, New York, USA
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Flores-Balcázar CH, Urías-Arce DM. Evaluation of Tumor Control and Normal Tissue Complication Probabilities in Patients Receiving Comprehensive Nodal Irradiation for Left-Sided Breast Cancer. Curr Oncol 2024; 31:3189-3198. [PMID: 38920725 PMCID: PMC11202494 DOI: 10.3390/curroncol31060241] [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: 04/02/2024] [Revised: 05/24/2024] [Accepted: 05/27/2024] [Indexed: 06/27/2024] Open
Abstract
Women with left-sided breast cancer receiving adjuvant radiotherapy have increased incidence of cardiac mortality due to ischemic heart disease; to date, no threshold dose for late cardiac/pulmonary morbidity or mortality has been established. We investigated the likelihood of cardiac death and radiation pneumonitis in women with left-sided breast cancer who received comprehensive lymph node irradiation. The differences in dosimetric parameters between free-breathing (FB) and deep inspiration breath hold (DIBH) techniques were also addressed. Based on NTCP calculations, the probability of cardiac death was significantly reduced with the DIBH compared to the FB technique (p < 0.001). The risk of radiation pneumonitis was not clinically significant. There was no difference in coverage between FB and DIBH plans. Doses to healthy structures were significantly lower in DIBH plan than in FB plan for V20, V30, and ipsilateral total lung volume. Inspiratory gating reduces the dose absorbed by the heart without compromising the target range, thus reducing the likelihood of cardiac death.
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Affiliation(s)
- Christian H. Flores-Balcázar
- Radiotherapy and Medical Physics Service, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City 14080, Mexico
- Radiotherapy Service, Instituto Nacional de Cancerología, Mexico City 14080, Mexico;
| | - Dulce M. Urías-Arce
- Radiotherapy Service, Instituto Nacional de Cancerología, Mexico City 14080, Mexico;
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Tzikas A, Lavdas E, Kechagias D, Mavroidis P. Dose-response modeling and treatment plan assessment with a python software toolkit. Med Dosim 2024; 49:340-352. [PMID: 38782687 DOI: 10.1016/j.meddos.2024.04.005] [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: 12/19/2023] [Revised: 04/16/2024] [Accepted: 04/17/2024] [Indexed: 05/25/2024]
Abstract
This software assistant aims at calculating the dose-response relations of tumors and normal tissues, or clinically assessing already determined values by other researchers. It can also indicate the optimal dose prescription by optimizing the expected treatment outcome. The software is developed solely in python programming language, and it employs PSFL license for its Graphical User Interface (GUI), NUMPY, MATPLOTLIB, and SCIPY libraries. It comprises of two components. The first is the Dose-response relations derivation component, which takes as input the dose volume histograms (DVHs) of patients and their recorded responses regarding a given clinical endpoint to determine the parameters of different tumor control probability (TCP) or normal tissue complication probability (NTCP) models. The second is the Treatment Plan Assessment component, which uses the DVHs of a plan and the dose-response parameters values of the involved tumors and organs at risk (OARs) to calculate their expected responses. Additionally, the overall probabilities of benefit (PB), injury (PI) and complication-free tumor control (P+) are calculated. The software calculates rapidly the corresponding generalized equivalent uniform doses (gEUD) and biologically effective uniform doses (D‾‾) for the Lyman-Kutcher-Burman (LKB), parallel volume (PV) and relative seriality (RS) models respectively, determining the model parameters. In the Dose-Response Relations Derivation component, the software plots the dose-response curves of the irradiated organ with the relevant confidence internals along with the data of the patients with and without toxicity. It also calculates the odds ratio (OR) and the area under the curve (AUC) of different dose metrics or model parameter values against the individual patient outcomes to determine their discrimination capacity. It also performs a goodness-of-fit evaluation of any model parameter set. The user has the option of viewing plots like Scatter, 3D surfaces, and Bootstrap plots. In the Treatment Plan Assessment part, the software calculates the TCP and NTCP values of the involved tumors and OARs, respectively. Furthermore, it plots the dose-response curves of the TCPs, NTCPs, PB, PI, and P+ for a range of prescription doses for different treatment plans. The presented software is ideal for efficiently conducting studies of radiobiological modeling. Furthermore, it is ideal for performing treatment plan assessment, comparison, and optimization studies.
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Affiliation(s)
- Athanasios Tzikas
- University of West Attica, Department of Biomedical Sciences, Athens, Greece
| | - Eleftherios Lavdas
- University of West Attica, Department of Biomedical Sciences, Athens, Greece
| | - Dimitrios Kechagias
- University of West Attica, Department of Biomedical Sciences, Athens, Greece
| | - Panayiotis Mavroidis
- Department of Radiation Oncology, University of North Carolina at Chapel Hill, NC.
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Maragno D, Buti G, Birbil Şİ, Liao Z, Bortfeld T, den Hertog D, Ajdari A. Embedding machine learning based toxicity models within radiotherapy treatment plan optimization. Phys Med Biol 2024; 69:075003. [PMID: 38412530 DOI: 10.1088/1361-6560/ad2d7e] [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: 10/16/2023] [Accepted: 02/27/2024] [Indexed: 02/29/2024]
Abstract
Objective.This study addresses radiation-induced toxicity (RIT) challenges in radiotherapy (RT) by developing a personalized treatment planning framework. It leverages patient-specific data and dosimetric information to create an optimization model that limits adverse side effects using constraints learned from historical data.Approach.The study uses the optimization with constraint learning (OCL) framework, incorporating patient-specific factors into the optimization process. It consists of three steps: optimizing the baseline treatment plan using population-wide dosimetric constraints; training a machine learning (ML) model to estimate the patient's RIT for the baseline plan; and adapting the treatment plan to minimize RIT using ML-learned patient-specific constraints. Various predictive models, including classification trees, ensembles of trees, and neural networks, are applied to predict the probability of grade 2+ radiation pneumonitis (RP2+) for non-small cell lung (NSCLC) cancer patients three months post-RT. The methodology is assessed with four high RP2+ risk NSCLC patients, with the goal of optimizing the dose distribution to constrain the RP2+ outcome below a pre-specified threshold. Conventional and OCL-enhanced plans are compared based on dosimetric parameters and predicted RP2+ risk. Sensitivity analysis on risk thresholds and data uncertainty is performed using a toy NSCLC case.Main results.Experiments show the methodology's capacity to directly incorporate all predictive models into RT treatment planning. In the four patients studied, mean lung dose and V20 were reduced by an average of 1.78 Gy and 3.66%, resulting in an average RP2+ risk reduction from 95% to 42%. Notably, this reduction maintains tumor coverage, although in two cases, sparing the lung slightly increased spinal cord max-dose (0.23 and 0.79 Gy).Significance.By integrating patient-specific information into learned constraints, the study significantly reduces adverse side effects like RP2+ without compromising target coverage. This unified framework bridges the gap between predicting toxicities and optimizing treatment plans in personalized RT decision-making.
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Affiliation(s)
- Donato Maragno
- Amsterdam Business School, University of Amsterdam, Amsterdam, The Netherlands
| | - Gregory Buti
- Massachusetts General Hospital and Harvard Medical School, Department of Radiation Oncology, Division of Radiation BioPhysics, Boston, MA, United States of America
| | - Ş İlker Birbil
- Amsterdam Business School, University of Amsterdam, Amsterdam, The Netherlands
| | - Zhongxing Liao
- University of Texas' MD Anderson Cancer Center, Department of Radiation Oncology, Division of Radiation Oncology, Houston, TX, United States of America
| | - Thomas Bortfeld
- Massachusetts General Hospital and Harvard Medical School, Department of Radiation Oncology, Division of Radiation BioPhysics, Boston, MA, United States of America
| | - Dick den Hertog
- Amsterdam Business School, University of Amsterdam, Amsterdam, The Netherlands
| | - Ali Ajdari
- Massachusetts General Hospital and Harvard Medical School, Department of Radiation Oncology, Division of Radiation BioPhysics, Boston, MA, United States of America
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Papanikolaou P, Swanson G, Stathakis S, Mavroidis P. NTCP Modeling and Dose-Volume Correlations of Significant Hematocrit Drop 3 Months After Prostate Radiation Therapy. Adv Radiat Oncol 2024; 9:101393. [PMID: 38292887 PMCID: PMC10823068 DOI: 10.1016/j.adro.2023.101393] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2023] [Accepted: 10/05/2023] [Indexed: 02/01/2024] Open
Abstract
Purpose Our purpose was to determine and model the dose-response relations of different parts of the pelvis regarding the endpoint of hematocrit level drop after pelvic radiation therapy (RT). Methods and Materials Two hundred and twenty-one patients treated with RT for prostate adenocarcinoma between 2014 and 2016 were included. All patients had complete blood counts collected at baseline and 3 months post-RT. The net difference of hematocrit level post-RT versus baseline was calculated, and the level of the 15th percentiles defined the thresholds of response in each case. The doses to 8 different pelvic structures were derived and fitted to the hematocrit levels using the relative seriality normal tissue complication probability model and the biologically equivalent uniform dose (D = ). Results Pelvic structures that correlated with significant decreases in hematocrit were the os coxae bilaterally superior to the acetabulum (OCUB), the total os coxae bilaterally, and the bone volume of the whole pelvis. The structure showing the highest correlation was OCUB with a maximum area under the curve (AUC) of 0.74. For V20 Gy < 30% the odds ratio was 9.8 with 95% CI of 2.9 to 32.9. For mean dose (Dmean) to OCUB, an AUC of 0.73 was observed where the dose threshold was 23 Gy and the odds ratio was 2.7 and 95% CI 1.3 to 5.6. The values for the D50, γ, and s parameters of the relative seriality model were 26.9 Gy (25.9-27.9), 1.3 (1.2-2.2), and 0.12 (0.10-0.83), respectively. The AUC of D = was 0.73 and patients with D = to OCUB ≥ 27 Gy had 8.2 times higher rate of significant hematocrit drop versus <27 Gy. Conclusions These findings confirm the association of radiation-induced damage to pelvic bone marrow with a drop in hematocrit. A threshold of V20 Gy < 30%, Dmean < 23 Gy, or D = < 27 Gy to OCUB may significantly reduce the risk for this endpoint.
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Affiliation(s)
- Panos Papanikolaou
- Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Gregory Swanson
- Department of Radiation Oncology, Baylor Scott & White Health, Temple, Texas
| | - Sotirios Stathakis
- Department of Physics, Mary Bird Perkins Cancer Center, Baton Rouge, Louisiana
| | - Panayiotis Mavroidis
- Department of Radiation Oncology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
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Bonaccorsi SG, Tessonnier T, Hoeltgen L, Meixner E, Harrabi S, Hörner-Rieber J, Haberer T, Abdollahi A, Debus J, Mairani A. Exploring Helium Ions' Potential for Post-Mastectomy Left-Sided Breast Cancer Radiotherapy. Cancers (Basel) 2024; 16:410. [PMID: 38254899 PMCID: PMC10814201 DOI: 10.3390/cancers16020410] [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: 10/16/2023] [Revised: 01/04/2024] [Accepted: 01/11/2024] [Indexed: 01/24/2024] Open
Abstract
Proton therapy presents a promising modality for treating left-sided breast cancer due to its unique dose distribution. Helium ions provide increased conformality thanks to a reduced lateral scattering. Consequently, the potential clinical benefit of both techniques was explored. An explorative treatment planning study involving ten patients, previously treated with VMAT (Volumetric Modulated Arc Therapy) for 50 Gy in 25 fractions for locally advanced, node-positive breast cancer, was carried out using proton pencil beam therapy with a fixed relative biological effectiveness (RBE) of 1.1 and helium therapy with a variable RBE described by the mMKM (modified microdosimetric kinetic model). Results indicated that target coverage was improved with particle therapy for both the clinical target volume and especially the internal mammary lymph nodes compared to VMAT. Median dose value analysis revealed that proton and helium plans provided lower dose on the left anterior descending artery (LAD), heart, lungs and right breast than VMAT. Notably, helium therapy exhibited improved ipsilateral lung sparing over protons. Employing NTCP models as available in the literature, helium therapy showed a lower probability of grade ≤ 2 radiation pneumonitis (22% for photons, 5% for protons and 2% for helium ions), while both proton and helium ions reduce the probability of major coronary events with respect to VMAT.
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Affiliation(s)
| | - Thomas Tessonnier
- Heidelberg Ion-Beam Therapy Center (HIT), Heidelberg University Hospital, 69120 Heidelberg, Germany
- Division of Molecular and Translational Radiation Oncology, National Center for Tumor Diseases (NCT), Heidelberg University Hospital, 69120 Heidelberg, Germany
| | - Line Hoeltgen
- Department of Radiation Oncology, Heidelberg University Hospital, 69120 Heidelberg, Germany
| | - Eva Meixner
- Department of Radiation Oncology, Heidelberg University Hospital, 69120 Heidelberg, Germany
| | - Semi Harrabi
- Department of Radiation Oncology, Heidelberg University Hospital, 69120 Heidelberg, Germany
| | - Juliane Hörner-Rieber
- Department of Radiation Oncology, Heidelberg University Hospital, 69120 Heidelberg, Germany
- Heidelberg Institute of Radiation Oncology (HIRO), German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
- Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
| | - Thomas Haberer
- Heidelberg Ion-Beam Therapy Center (HIT), Heidelberg University Hospital, 69120 Heidelberg, Germany
| | - Amir Abdollahi
- Heidelberg Ion-Beam Therapy Center (HIT), Heidelberg University Hospital, 69120 Heidelberg, Germany
- Division of Molecular and Translational Radiation Oncology, National Center for Tumor Diseases (NCT), Heidelberg University Hospital, 69120 Heidelberg, Germany
- Heidelberg Institute of Radiation Oncology (HIRO), German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
- German Cancer Consortium (DKTK), 69120 Heidelberg, Germany
| | - Jürgen Debus
- Heidelberg Ion-Beam Therapy Center (HIT), Heidelberg University Hospital, 69120 Heidelberg, Germany
- Department of Radiation Oncology, Heidelberg University Hospital, 69120 Heidelberg, Germany
- Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
- German Cancer Consortium (DKTK), 69120 Heidelberg, Germany
| | - Andrea Mairani
- Heidelberg Ion-Beam Therapy Center (HIT), Heidelberg University Hospital, 69120 Heidelberg, Germany
- Division of Molecular and Translational Radiation Oncology, National Center for Tumor Diseases (NCT), Heidelberg University Hospital, 69120 Heidelberg, Germany
- Centro Nazionale di Adroterapia Oncologica (CNAO), 27100 Pavia, Italy
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11
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Heuchel L, Hahn C, Ödén J, Traneus E, Wulff J, Timmermann B, Bäumer C, Lühr A. The dirty and clean dose concept: Towards creating proton therapy treatment plans with a photon-like dose response. Med Phys 2024; 51:622-636. [PMID: 37877574 DOI: 10.1002/mp.16809] [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: 07/03/2023] [Revised: 10/11/2023] [Accepted: 10/11/2023] [Indexed: 10/26/2023] Open
Abstract
BACKGROUND Applying tolerance doses for organs at risk (OAR) from photon therapy introduces uncertainties in proton therapy when assuming a constant relative biological effectiveness (RBE) of 1.1. PURPOSE This work introduces the novel dirty and clean dose concept, which allows for creating treatment plans with a more photon-like dose response for OAR and, thus, less uncertainties when applying photon-based tolerance doses. METHODS The concept divides the 1.1-weighted dose distribution into two parts: the clean and the dirty dose. The clean and dirty dose are deposited by protons with a linear energy transfer (LET) below and above a set LET threshold, respectively. For the former, a photon-like dose response is assumed, while for the latter, the RBE might exceed 1.1. To reduce the dirty dose in OAR, a MaxDirtyDose objective was added in treatment plan optimization. It requires setting two parameters: LET threshold and max dirty dose level. A simple geometry consisting of one target volume and one OAR in water was used to study the reduction in dirty dose in the OAR depending on the choice of the two MaxDirtyDose objective parameters during plan optimization. The best performing parameter combinations were used to create multiple dirty dose optimized (DDopt) treatment plans for two cranial patient cases. For each DDopt plan, 1.1-weighted dose, variable RBE-weighted dose using the Wedenberg RBE model and dose-average LETd distributions as well as resulting normal tissue complication probability (NTCP) values were calculated and compared to the reference plan (RefPlan) without MaxDirtyDose objectives. RESULTS In the water phantom studies, LET thresholds between 1.5 and 2.5 keV/µm yielded the best plans and were subsequently used. For the patient cases, nearly all DDopt plans led to a reduced Wedenberg dose in critical OAR. This reduction resulted from an LET reduction and translated into an NTCP reduction of up to 19 percentage points compared to the RefPlan. The 1.1-weighted dose in the OARs was slightly increased (patient 1: 0.45 Gy(RBE), patient 2: 0.08 Gy(RBE)), but never exceeded clinical tolerance doses. Additionally, slightly increased 1.1-weighted dose in healthy brain tissue was observed (patient 1: 0.81 Gy(RBE), patient 2: 0.53 Gy(RBE)). The variation of NTCP values due to variation of α/β from 2 to 3 Gy was much smaller for DDopt (2 percentage points (pp)) than for RefPlans (5 pp). CONCLUSIONS The novel dirty and clean dose concept allows for creating biologically more robust proton treatment plans with a more photon-like dose response. The reduced uncertainties in RBE can, therefore, mitigate uncertainties introduced by using photon-based tolerance doses for OAR.
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Affiliation(s)
- Lena Heuchel
- Department of Physics, TU Dortmund University, Dortmund, Germany
| | - Christian Hahn
- Department of Physics, TU Dortmund University, Dortmund, Germany
- OncoRay-National Center of Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany
- Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
| | - Jakob Ödén
- RaySearch Laboratories AB, Stockholm, Sweden
| | | | - Jörg Wulff
- West German Proton Therapy Center Essen, Essen, Germany
- West German Cancer Center (WTZ), University Hospital Essen, Essen, Germany
| | - Beate Timmermann
- West German Proton Therapy Center Essen, Essen, Germany
- West German Cancer Center (WTZ), University Hospital Essen, Essen, Germany
- Department of Particle Therapy, University Hospital Essen, Essen, Germany
- German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Essen, Germany
| | - Christian Bäumer
- Department of Physics, TU Dortmund University, Dortmund, Germany
- West German Proton Therapy Center Essen, Essen, Germany
- West German Cancer Center (WTZ), University Hospital Essen, Essen, Germany
- German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Essen, Germany
| | - Armin Lühr
- Department of Physics, TU Dortmund University, Dortmund, Germany
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Tang C, Yuan J, Guo H, Dai Z, Liu B, Xi H, He J, Niu S. Quantify the Effect of Air Gap Errors on Skin Dose for Breast Cancer Radiotherapy. Technol Cancer Res Treat 2024; 23:15330338241258566. [PMID: 38803305 PMCID: PMC11135118 DOI: 10.1177/15330338241258566] [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] [Indexed: 05/29/2024] Open
Abstract
Purpose: Determining the impact of air gap errors on the skin dose in postoperative breast cancer radiotherapy under dynamic intensity-modulated radiation therapy (IMRT) techniques. Methods: This was a retrospective study that involved 55 patients who underwent postoperative radiotherapy following modified radical mastectomy. All plans employed tangential IMRT, with a prescription dose of 50 Gy, and bolus added solely to the chest wall. Simulated air gap depth errors of 2 mm, 3 mm, and 5 mm were introduced at depression or inframammary fold areas on the skin, resulting in the creation of air gaps named Air2, Air3, and Air5. Utilizing a multivariable GEE, the average dose (Dmean) of the local skin was determined to evaluate its relationship with air gap volume and the lateral beam's average angle (AALB). Additionally, an analysis was conducted on the impact of gaps on local skin. Results: When simulating an air gap depth error of 2 mm, the average Dmean in plan2 increased by 0.46 Gy compared to the initial plan (planO) (p < .001). For the 3-mm air gap, the average Dmean of plan3 was 0.51 Gy higher than that of planO (p < .001). When simulating the air gap as 5 mm, the average Dmean of plan5 significantly increased by 0.59 Gy compared to planO (p < .001). The TCP results showed a similar trend to those of Dmean. As the depth of air gap error increases, NTCP values also gradually rise. The linear regression of the multivariable GEE equation indicates that the volume of air gaps and the AALB are strong predictors of Dmean. Conclusion: With small irregular air gap errors simulated in 55 patients, the values of skin's Dmean, TCP, and NTCP increased. A multivariable linear GEE regression model may effectively explain the impact of air gap volume and AALB on the local skin.
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Affiliation(s)
- Chunbo Tang
- Department of Radiation Oncology, First Affiliated Hospital of Gannan Medical University, Ganzhou, China
- Jiangxi Clinical Research Center for Cancer, Ganzhou, China
| | - Jun Yuan
- Department of Radiation Oncology, First Affiliated Hospital of Gannan Medical University, Ganzhou, China
- Jiangxi Clinical Research Center for Cancer, Ganzhou, China
| | - Hailiang Guo
- Department of Radiation Oncology, First Affiliated Hospital of Gannan Medical University, Ganzhou, China
- Jiangxi Clinical Research Center for Cancer, Ganzhou, China
| | - Zhongyang Dai
- Department of Radiation Oncology, First Affiliated Hospital of Gannan Medical University, Ganzhou, China
- Jiangxi Clinical Research Center for Cancer, Ganzhou, China
| | - Biaoshui Liu
- Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Haiyan Xi
- Department of Radiation Oncology, Nanchang People's Hospital, Nanchang, China
| | - Ji He
- School of Biomedical Engineering, Fourth Affiliated Hospital of Guangzhou, Guangzhou Medical University, Guangzhou, China
| | - Shanzhou Niu
- School of Mathematics and Computer Science / Ganzhou Key Laboratory of Computational Imaging, Gannan Normal University, Ganzhou, China
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Tzikas A, Lavdas E, Kehagias D, Amdur R, Mendenhall W, Sheets N, Green R, Chera B, Mavroidis P. NTCP modelling of xerostomia after radiotherapy for oropharyngeal cancer using the PRO-CTCAE and CTCAE scoring systems at different time-points post-RT. Phys Med 2023; 116:103169. [PMID: 37989042 DOI: 10.1016/j.ejmp.2023.103169] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2023] [Revised: 09/30/2023] [Accepted: 11/05/2023] [Indexed: 11/23/2023] Open
Abstract
PURPOSE This study aims at determining the parameter values of three normal tissue complication probability (NTCP) models for the contralateral parotid gland, contralateral submandibular gland (SMG) and contralateral salivary glands regarding the endpoint of xerostomia 6-24 months after radiotherapy for oropharynx cancer. METHODS The treatment and outcome data of 231 patients with favorable risk, HPV-associated oropharyngeal squamous cell carcinoma are analyzed. 60 Gy intensity modulated radiotherapy was delivered to all the patients. The presence and severity of xerostomia was recorded (pre- and post- radiotherapy) by the PRO-CTCAE and the CTCAE scoring systems. In both scoring systems, patients with a change in symptom severity (from baseline) of ≥ 2 were considered responders. RESULTS Xerostomia was observed in 61.3 %, 39.2 %, 28.6 % and 27.0 % of the patients based on the PRO-CTCAE scoring system at 6-, 12-, 18- and 24-months post-RT, respectively. The AUCs of the contralateral salivary glands ranged between 0.58-0.64 in the LKB model with the gEUD ranging between 20.3 Gy and 24.7 Gy. CONCLUSIONS Based on the PRO-CTCAE scores, mean dose < 22 Gy, V50 < 10 % for the contralateral salivary glands and mean dose < 18 Gy, V45 < 10 % for the contralateral parotid were found to significantly reduce by a factor of 2-3 the risk for radiation induced xerostomia that is observed at 6-24 months post-RT, respectively. Also, gEUD < 22 Gy to the contralateral salivary glands and < 18 Gy to the contralateral parotid was found to significantly reduce the risk for radiation induced xerostomia that is observed at 6-24 months post-RT by 2.0-2.3 times.
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Affiliation(s)
- Athanasios Tzikas
- University of West Attica, Department of Biomedical Sciences, Athens, Greece
| | - Eleftherios Lavdas
- University of West Attica, Department of Biomedical Sciences, Athens, Greece
| | - Dimitrios Kehagias
- University of West Attica, Department of Biomedical Sciences, Athens, Greece
| | - Robert Amdur
- Department of Radiation Oncology, University of Florida Hospitals, Gainesville, FL, United States
| | - William Mendenhall
- Department of Radiation Oncology, University of Florida Hospitals, Gainesville, FL, United States
| | - Nathan Sheets
- Department of Radiation Oncology, University of North Carolina at Chapel Hill, NC, United States
| | - Rebecca Green
- Department of Radiation Oncology, University of North Carolina at Chapel Hill, NC, United States
| | - Bhishamjit Chera
- Department of Radiation Oncology, MUSC Hollings Cancer Center, Charleston, SC, United States
| | - Panayiotis Mavroidis
- Department of Radiation Oncology, University of North Carolina at Chapel Hill, NC, United States.
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Tajiki S, Joya M, Gharekhani V, Richeson D, Gholami S. A systematic review of the normal tissue complication probability models and parameters: Head and neck cancers treated with conformal radiotherapy. Head Neck 2023; 45:3146-3156. [PMID: 37767820 DOI: 10.1002/hed.27469] [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: 03/24/2023] [Revised: 07/05/2023] [Accepted: 07/06/2023] [Indexed: 09/29/2023] Open
Abstract
This systematic review study aims to provide comprehensive data on different radiobiological models, parameters, and endpoints used for calculating the normal tissue complication probability (NTCP) based on clinical data from head and neck cancer patients treated with conformal radiotherapy. A systematic literature search was carried out according to the PRISMA guideline for the identification of relevant publications in six electronic databases of Embase, PubMed, Scopus, and Google Scholar to July 2022 using specific keywords in the paper's title and abstract. The initial search resulted in 1368 articles for all organs for the review article about the NTCP parameters. One hundred and seventy-eight articles were accepted for all organs with complete parameters for the mentioned models and finally, 20 head and neck cancer articles were accepted for review. Analysis of the studies shows that the Lyman-Kutcher-Burman (LKB) model properly links the NTCP curve parameters to the postradiotherapy endpoints. In the LKB model for esophagus, the minimum, and maximum corresponding parameters were reported as TD50 = 2.61 Gy with grade ≥3 radiation-induced esophagitis endpoints as the minimum TD50 and TD50 = 68 Gy as the maximum ones. nmin = 0.06, nmax = 1.04, mmin = 0.1, and mmax = 0.65, respectively. Unfortunately, there was not a wide range of published articles on other organs at risk like ear or cauda equina except Burman et al. (Fitting of normal tissue tolerance data to an analytic function. Int J Radiat Oncol Biol Phys Ther. 1991;21:123-135). Findings suggest that the validation of different radiobiological models and their corresponding parameters need to be investigated in vivo and in vitro for developing a more accurate NTCP model to be used for radiotherapy treatment planning optimization.
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Affiliation(s)
- Sareh Tajiki
- Radiotherapy Oncology Research Centre, Cancer Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Musa Joya
- Department of Medical Physics and Biomedical Engineering, Tehran University of Medical Sciences, Tehran, Iran
| | - Vahideh Gharekhani
- Department of Radiobiology, Faculty of Paramedical, Tehran University of Medical Sciences, Tehran, Iran
| | - Dylan Richeson
- Department of Radiation Oncology, Virginia Commonwealth University, Richmond, Virginia, USA
| | - Somayeh Gholami
- Department of Radiation Oncology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA
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Hernández KVD, Unterkirhers S, Schneider U. Quality assessment of automatically planned O-Ring linac SBRT plans for pelvic lymph node metastases, finding the optimal minimum target size by comparison with robotic SBRT. J Appl Clin Med Phys 2023; 24:e14143. [PMID: 37738649 PMCID: PMC10691630 DOI: 10.1002/acm2.14143] [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: 02/20/2023] [Revised: 08/18/2023] [Accepted: 08/21/2023] [Indexed: 09/24/2023] Open
Abstract
PURPOSE The purpose of this study is to assess the quality of automatic planned O-Ring Halcyon linac SBRT plans for pelvic lymph node metastases and to establish an absolute PTV volume threshold as a plan quality prediction criterion. Compliance of the plans to institutional SBRT plan evaluation criteria and differences in plan quality and treatment delivery times between Halcyon Linac and CyberKnife robotic SBRT were evaluated. METHODS Twenty-one CyberKnife treatment plans were replanned for Halcyon. Prescription doses range was 26-40 Gy in mean three fractions. The mean/median planning target volume was 4.0/3.6 cm3 . Institutional criteria for the plan evaluation were: New Conformity Index (NCI), Conformity Index (CI), Modified Gradient Index (MGI), selectivity index reciprocal (PIV/TVPIV ), and the target coverage by prescription isodose (%PIV). Statistical analysis based on the receiver operating characteristic (ROC) curve was used to determine a plan quality predictor threshold of the PTV volume. Comparative analysis of normal tissue complication probabilities (NTCP) was used to assess the risk of toxicity in healthy tissues. RESULTS Seventy-one percent (n = 15)/95% (n = 20) of Halcyon and 81% (n = 17)/100% (n = 21) of CK plans fulfilled all ideal/tolerance criteria. For PTVs above a found optimal threshold of 2.6 cm3 (71%, n = 15), no statistically significant difference was observed between the CI, NCI, PIV/TVPIV , and MGI indexes of both groups, while the coverage (%PIV) was statistically but not clinically significantly different between cohorts. Significantly shorter delivery times are expected with Halcyon. No significant differences in NTCP were observed. CONCLUSION All but one automatically optimized Halcyon treatment plans demonstrated ideal or acceptable performance. PTV threshold of 2.6 cm3 can be used as decision criteria in clinical settings. The results of our study demonstrated the promising performance of the Halcyon for pelvic SBRT, although plan-specific QA is required to verify machine performance during plan delivery.
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Affiliation(s)
| | | | - Uwe Schneider
- Science FacultyUniversity of ZürichZürichSwitzerland
- Medical PhysicsRadiotherapy HirslandenZürichSwitzerland
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SHIRATO H. Biomedical advances and future prospects of high-precision three-dimensional radiotherapy and four-dimensional radiotherapy. PROCEEDINGS OF THE JAPAN ACADEMY. SERIES B, PHYSICAL AND BIOLOGICAL SCIENCES 2023; 99:389-426. [PMID: 37821390 PMCID: PMC10749389 DOI: 10.2183/pjab.99.024] [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: 07/26/2023] [Accepted: 09/13/2023] [Indexed: 10/13/2023]
Abstract
Biomedical advances of external-beam radiotherapy (EBRT) with improvements in physical accuracy are reviewed. High-precision (±1 mm) three-dimensional radiotherapy (3DRT) can utilize respective therapeutic open doors in the tumor control probability curve and in the normal tissue complication probability curve instead of the one single therapeutic window in two-dimensional EBRT. High-precision 3DRT achieved higher tumor control and probable survival rates for patients with small peripheral lung and liver cancers. Four-dimensional radiotherapy (4DRT), which can reduce uncertainties in 3DRT due to organ motion by real-time (every 0.1-1 s) tumor-tracking and immediate (0.1-1 s) irradiation, have achieved reduced adverse effects for prostate and pancreatic tumors near the digestive tract and with similar or better tumor control. Particle beam therapy improved tumor control and probable survival for patients with large liver tumors. The clinical outcomes of locally advanced or multiple tumors located near serial-type organs can theoretically be improved further by integrating the 4DRT concept with particle beams.
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Affiliation(s)
- Hiroki SHIRATO
- Global Center for Biomedical Science and Engineering, Faculty of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan
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Momeni N, Broomand MA, Roozmand Z, Hamzian N. Estimating the Dose-Response Relationship for Ocular Pain after Radiotherapy of Head and Neck Cancers and Skull Base Tumors based on the LKB Radiobiological Model. J Biomed Phys Eng 2023; 13:411-420. [PMID: 37868939 PMCID: PMC10589689 DOI: 10.31661/jbpe.v0i0.2210-1554] [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: 10/24/2022] [Accepted: 01/03/2023] [Indexed: 10/24/2023]
Abstract
Background Radiotherapy is considered a compromise between the amount of killed tumor cells and the damage caused to the healthy tissue. Regarding this, radiobiological modeling is performed to individualize and optimize treatment strategies. Objective This study aimed to determine the normal tissue complication probability (NTCP) of acute ocular pain following radiotherapy. Material and Methods In this prospective observational study, the clinical data were collected from 45 patients with head and neck cancers and skull-base tumors, and dosimetric data were recorded after contouring the eye globe. Acute ocular pain was prospectively assessed with a three-month follow-up. The Lyman-Kutcher-Berman (LKB) parameters were estimated using the Area Under Curve (AUC) of Receiver Operating Characteristic (ROC) maximization and Maximum Likelihood (MLH) methods, and the NTCP of acute ocular pain was then determined using generalized LKB radiobiological model. The model performance was evaluated with AUC, Brier score, and Hosmer-Lemeshow tests. Results Six out of 45 (13.33%) patients developed acute ocular pain (grade 1 or more). LKB model showed a weak dose-volume effect (n=0.09), tolerance dose for a 50% complication (TD50) of 27.54 Gy, and slope parameter (m) of 0.38. The LKB model showed high prediction performance. The LKB model predicted that NTCP would be less than 25% if the generalized equivalent uniform dose (gEUD) was kept below 20 Gy. Conclusion The LKB model showed a high performance in determining the NTCP of ocular pain so that the probability of ocular pain will be less than 25% if the eye globe mean dose is kept below 12 Gy.
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Affiliation(s)
- Nastaran Momeni
- Department of Medical Physics, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Mohammad Ali Broomand
- Department of Clinical Oncology, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Zahra Roozmand
- Department of Medical Physics, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Nima Hamzian
- Department of Medical Physics, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
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Jaafar AM, Arif RK, Ahmed S, Alabedi HH, Khalil MM, Yaseen MN, Ammar H. Comparing biological and physical cost functions in VMAT planning for pediatric nasopharyngeal cancer. J Med Imaging Radiat Sci 2023; 54:473-480. [PMID: 37481373 DOI: 10.1016/j.jmir.2023.07.002] [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: 12/26/2022] [Revised: 06/29/2023] [Accepted: 07/04/2023] [Indexed: 07/24/2023]
Abstract
BACKGROUND Volumetric Modulated Arc Therapy (VMAT) is an option for the delivery of Radiotherapy treatment technique for pediatric nasopharyngeal cancer, VMAT is the most common treatment technique for pediatric nasopharyngeal cancer. The use of a combination of both biological and physical parameters in VMAT planning optimization may produce better target coverage and sparing of critical organs. This work was to compare Biological Cost Functions (BCFs) and Physical Cost Functions (PCFs) in the VMAT of pediatric nasopharyngeal cancer patients. METHOD VMAT plans for 20 nasopharyngeal pediatric cancer patients were created using Monaco 5.11® treatment planning system (TPS). Three VMAT plans were retrospectively generated for each patient using BCFs, PCFs and mixed plan with a total dose of 61.2 Gy in 34 fractions to planning target volume (PTV). All plans were adjusted to deliver 95% of the prescribed dose to 95% of the PTV. The calculated plans were qualitatively and quantitatively evaluated using the dose-volume histogram (DVH). RESULTS The coverage of the target and the maximum dose for the three plans were nearly the same, and better sparing was achieved in the serial organs (spinal cord and brain stem) with PCFs. On the contrary, more dose spring was observed using the BCFs in the organs at risk (OARs) that were not involved in the dose optimization, such as the optic nerve maximum dose, with a significant p-value (0.035 and 0.0001) respectively. Using the PCFs, both parotids received a lower mean dose, but not for the oral cavity, which had a lower mean dose using BCFs (p=<0.0001). The same values of tumor control probability (TCP) were found for both cost functions in PTVs and normal tissue complications probability (NTCP) (99%). The values reported were as follows: spinal cord = 0.5%, brain stem = 19.1%, and brain = 90.7% for BCFs, compared to spinal cord = 0.3%, brain stem = 14.9%, and brain = 90.7% for PCFs. The delivery time was found to be less in BCFs (p=0.005). CONCLUSION The BCFs are superior to the PCFs in conformity index and time of radiation delivery. However, PCFs were better at dose sparing for the serial organs and achieving a sharper falloff dose around the involved volumes. A patient-specific clinical compromise is recommended to gain the best plan that meets the clinical goals.
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Affiliation(s)
- Ahmed Mousa Jaafar
- Department of Physics, Faculty of Science, Helwan University, Egypt; Baghdad Center for Radiotherapy and Nuclear Medicine, Medical City, Iraq.
| | - Ruba K Arif
- Department of Physics, Faculty of Science, Helwan University, Egypt; Baghdad Center for Radiotherapy and Nuclear Medicine, Medical City, Iraq.
| | - Soha Ahmed
- Clinical oncology, Faculty of Medicine, Suze University, Egypt.
| | | | - Magdy M Khalil
- Department of Physics, Faculty of Science, Helwan University, Egypt; School of Biotechnology, Badr University in Cairo (BUC), Egypt.
| | | | - Hany Ammar
- Radiation Oncology Department, Children's Cancer Hospital, 57357, Egypt; Clinical Oncology Department, Faculty of Medicine, Aswan University, Egypt.
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19
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Momeni N, Ali Boroomand M, Roozmand Z, Namiranian N, Hamzian N. Normal tissue complication probability of acute eyelids erythema following radiotherapy of head and neck cancers and skull-base tumors. Phys Med 2023; 112:102621. [PMID: 37329741 DOI: 10.1016/j.ejmp.2023.102621] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2023] [Revised: 06/04/2023] [Accepted: 06/06/2023] [Indexed: 06/19/2023] Open
Abstract
PURPOSE Radiation therapy is broadly used as one of the main treatment methods for patients with head and neck cancers and skull base tumors. However, it can lead to normal tissue complications. Therefore, this study aimed to model normal tissue complication probability (NTCP) of eyelid skin erythema after radiation therapy. METHODS The dataset of 45 patients with head and neck and skull base tumors was prospectively collected from their dose-volume histograms (DVHs). Grade 1 + eyelid skin erythema based on the Common Terminology Criteria for Adverse Events (CTCAE 4.0) was evaluated as the endpoint after a three-month follow-up. The Lyman-Kutcher-Burman (LKB) radiobiological model was developed based on generalized equivalent uniform dose (gEUD). Model parameters were calculated by maximum likelihood estimation. Model performance was evaluated by ROC-AUC, Brier score and Hosmer-Lemeshow test. RESULTS After three months of follow-up, 13.33% of patients experienced eyelids skin erythema grade 1 or more. The parameters of the LKB model were: TD50 = 30 Gy, m = 0.14, and n = 0.10. The model showed good predictive performance with ROC-AUC = 0.80 (CI:0.66-0.94) and a Brier score of 0.20. CONCLUSIONS In this study, NTCP of eyelid skin erythema was modeled based on the LKB radiobiological model with good predictive performance.
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Affiliation(s)
- Nastaran Momeni
- Department of Medical Physics, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Mohammad Ali Boroomand
- Clinical oncology department, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Zahra Roozmand
- Department of Medical Physics, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Nasim Namiranian
- Diabetes research center of Alikhani, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Nima Hamzian
- Department of Medical Physics, School of Medicine, Shahid Sadoughi Universi of Medical Sciences, Yazd, Iran.
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20
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Racka I, Majewska K, Winiecki J. Three-dimensional conformal radiotherapy (3D-CRT) vs. volumetric modulated arc therapy (VMAT) in deep inspiration breath-hold (DIBH) technique in left-sided breast cancer patients-comparative analysis of dose distribution and estimation of projected secondary cancer risk. Strahlenther Onkol 2023; 199:90-101. [PMID: 35943553 DOI: 10.1007/s00066-022-01979-2] [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: 12/23/2021] [Accepted: 07/07/2022] [Indexed: 01/18/2023]
Abstract
PURPOSE The purpose of this study was to compare two techniques of irradiation of left-sided breast cancer patients who underwent breast-conserving surgery, three-dimensional conformal radiotherapy technique (3D-CRT) and volumetric modulated arc therapy (VMAT), in terms of dose distribution in the planning target volume (PTV) and organs at risk (OARs). The second aim of the study was estimation of the projected risk of radiation-induced secondary cancer for both radiotherapy techniques. MATERIALS AND METHODS For 25 patients who underwent CT simulation in deep inspiration breath-hold (DIBH), three treatment plans were generated: one using a three-dimensional conformal radiotherapy technique and two using volumetric modulated arc therapy. First VMAT-DIBH geometry consisted of three partial arcs (ARC-DIBH 3A) and second consisted of four partial arcs (ARC-DIBH 4A). Cumulative dose-volume histograms (DVHs) were used to compare dose distributions within the PTV and OARs (heart, left anterior descending coronary artery [LAD], ipsilateral and contralateral lung [IL, CL], and contralateral breast [CB]). Normal tissue complication probabilities (NTCPs) and organ equivalent doses (OEDs) were calculated using the differential DVHs. Excess absolute risks (EARs) for second cancers were estimated using Schneider's full mechanistic dose-response model. RESULTS All plans fulfilled the criterium for PTV V95% ≥ 95%. The PTV coverage, homogeneity, and conformity indices were significantly better for VMAT-DIBH. VMAT showed a significantly increased mean dose and V5Gy for all OARs, but reduced LAD Dmax by 15 Gy. For IL, CL, and CB, the 3D-CRT DIBH method achieved the lowest values of EAR: 28.38 per 10,000 PYs, 2.55 per 10,000 PYs, and 4.48 per 10,000 PYs (p < 0.001), compared to 40.29 per 10,000 PYs, 15.62 per 10,000 PYs, and 23.44 per 10,000 PYs for ARC-DIBH 3A plans and 41.12 per 10,000 PYs, 15.59 per 10,000 PYs, and 22.73 per 10,000 PYs for ARC-DIBH 4A plans. Both techniques provided negligibly low NTCPs for all OARs. CONCLUSION The study shows that VMAT-DIBH provides better OAR sparing against high doses. However, the large low-dose-bath (≤ 5 Gy) is still a concern due to the fact that a larger volume of normal tissues exposed to lower doses may increase a radiation-induced risk of secondary cancer.
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Affiliation(s)
- Iga Racka
- Medical Physics Department, Prof. Franciszek Łukaszczyk Memorial Oncology Centre in Bydgoszcz, Bydgoszcz, Poland.
| | - Karolina Majewska
- Medical Physics Department, Prof. Franciszek Łukaszczyk Memorial Oncology Centre in Bydgoszcz, Bydgoszcz, Poland
| | - Janusz Winiecki
- Medical Physics Department, Prof. Franciszek Łukaszczyk Memorial Oncology Centre in Bydgoszcz, Bydgoszcz, Poland.,Clinic of Oncology and Brachytherapy, Collegium Medicum in Bydgoszcz, Nicholas Copernicus University in Torun, Bydgoszcz, Poland
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21
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Hahn C, Heuchel L, Ödén J, Traneus E, Wulff J, Plaude S, Timmermann B, Bäumer C, Lühr A. Comparing biological effectiveness guided plan optimization strategies for cranial proton therapy: potential and challenges. Radiat Oncol 2022; 17:169. [PMID: 36273132 DOI: 10.1186/s13014-022-02143-x] [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: 05/19/2022] [Accepted: 10/10/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND To introduce and compare multiple biological effectiveness guided (BG) proton plan optimization strategies minimizing variable relative biological effectiveness (RBE) induced dose burden in organs at risk (OAR) while maintaining plan quality with a constant RBE. METHODS Dose-optimized (DOSEopt) proton pencil beam scanning reference treatment plans were generated for ten cranial patients with prescription doses ≥ 54 Gy(RBE) and ≥ 1 OAR close to the clinical target volume (CTV). For each patient, four additional BG plans were created. BG objectives minimized either proton track-ends, dose-averaged linear energy transfer (LETd), energy depositions from high-LET protons or variable RBE-weighted dose (DRBE) in adjacent serially structured OARs. Plan quality (RBE = 1.1) was assessed by CTV dose coverage and robustness (2 mm setup, 3.5% density), dose homogeneity and conformity in the planning target volumes and adherence to OAR tolerance doses. LETd, DRBE (Wedenberg model, α/βCTV = 10 Gy, α/βOAR = 2 Gy) and resulting normal tissue complication probabilities (NTCPs) for blindness and brainstem necrosis were derived. Differences between DOSEopt and BG optimized plans were assessed and statistically tested (Wilcoxon signed rank, α = 0.05). RESULTS All plans were clinically acceptable. DOSEopt and BG optimized plans were comparable in target volume coverage, homogeneity and conformity. For recalculated DRBE in all patients, all BG plans significantly reduced near-maximum DRBE to critical OARs with differences up to 8.2 Gy(RBE) (p < 0.05). Direct DRBE optimization primarily reduced absorbed dose in OARs (average ΔDmean = 2.0 Gy; average ΔLETd,mean = 0.1 keV/µm), while the other strategies reduced LETd (average ΔDmean < 0.3 Gy; average ΔLETd,mean = 0.5 keV/µm). LET-optimizing strategies were more robust against range and setup uncertaintes for high-dose CTVs than DRBE optimization. All BG strategies reduced NTCP for brainstem necrosis and blindness on average by 47% with average and maximum reductions of 5.4 and 18.4 percentage points, respectively. CONCLUSIONS All BG strategies reduced variable RBE-induced NTCPs to OARs. Reducing LETd in high-dose voxels may be favourable due to its adherence to current dose reporting and maintenance of clinical plan quality and the availability of reported LETd and dose levels from clinical toxicity reports after cranial proton therapy. These optimization strategies beyond dose may be a first step towards safely translating variable RBE optimization in the clinics.
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Affiliation(s)
- Christian Hahn
- Department of Physics, TU Dortmund University, Dortmund, Germany. .,OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany. .,Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
| | - Lena Heuchel
- Department of Physics, TU Dortmund University, Dortmund, Germany
| | - Jakob Ödén
- RaySearch Laboratories AB, Stockholm, Sweden
| | | | - Jörg Wulff
- West German Proton Therapy Centre Essen, Essen, Germany.,West German Cancer Center (WTZ), University Hospital Essen, Essen, Germany
| | - Sandija Plaude
- West German Proton Therapy Centre Essen, Essen, Germany.,West German Cancer Center (WTZ), University Hospital Essen, Essen, Germany
| | - Beate Timmermann
- West German Proton Therapy Centre Essen, Essen, Germany.,West German Cancer Center (WTZ), University Hospital Essen, Essen, Germany.,Department of Particle Therapy, University Hospital Essen, Essen, Germany.,German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Christian Bäumer
- Department of Physics, TU Dortmund University, Dortmund, Germany.,West German Proton Therapy Centre Essen, Essen, Germany.,West German Cancer Center (WTZ), University Hospital Essen, Essen, Germany.,German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Armin Lühr
- Department of Physics, TU Dortmund University, Dortmund, Germany
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22
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Cui Y, Pan Y, Li Z, Wu Q, Zou J, Han D, Yin Y, Ma C. Dosimetric analysis and biological evaluation between proton radiotherapy and photon radiotherapy for the long target of total esophageal squamous cell carcinoma. Front Oncol 2022; 12:954187. [PMID: 36263217 PMCID: PMC9574336 DOI: 10.3389/fonc.2022.954187] [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: 05/27/2022] [Accepted: 09/05/2022] [Indexed: 11/13/2022] Open
Abstract
Objective The purpose of this study is to compare the dosimetric and biological evaluation differences between photon and proton radiation therapy. Methods Thirty esophageal squamous cell carcinoma (ESCC) patients were generated for volumetric modulated arc therapy (VMAT) planning and intensity-modulated proton therapy (IMPT) planning to compare with intensity-modulated radiation therapy (IMRT) planning. According to dose–volume histogram (DVH), dose–volume parameters of the plan target volume (PTV) and homogeneity index (HI), conformity index (CI), and gradient index (GI) were used to analyze the differences between the various plans. For the organs at risk (OARS), dosimetric parameters were compared. Tumor control probability (TCP) and normal tissue complication probability (NTCP) was also used to evaluate the biological effectiveness of different plannings. Results CI, HI, and GI of IMPT planning were significantly superior in the three types of planning (p < 0.001, p < 0.001, and p < 0.001, respectively). Compared to IMRT and VMAT planning, IMPT planning improved the TCP (p<0.001, p<0.001, respectively). As for OARs, IMPT reduced the bilateral lung and heart accepted irradiation dose and volume. The dosimetric parameters, such as mean lung dose (MLD), mean heart dose (MHD), V5, V10, and V20, were significantly lower than IMRT or VMAT. IMPT afforded a lower maximum dose (Dmax) of the spinal cord than the other two-photon plans. What’s more, the radiation pneumonia of the left lung, which was caused by IMPT, was lower than IMRT and VMAT. IMPT achieved the pericarditis probability of heart is only 1.73% ± 0.24%. For spinal cord myelitis necrosis, there was no significant difference between the three different technologies. Conclusion Proton radiotherapy is an effective technology to relieve esophageal cancer, which could improve the TCP and spare the heart, lungs, and spinal cord. Our study provides a prediction of radiotherapy outcomes and further guides the individual treatment.
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Affiliation(s)
- Yongbin Cui
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
| | - Yuteng Pan
- Medical Science and Technology Innovation Center, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
| | - Zhenjiang Li
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
| | - Qiang Wu
- Affiliated Hospital of Weifang Medical University, School of Clinical Medicine, Weifang Medical University, Weifang, China
| | - Jingmin Zou
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
| | - Dali Han
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
| | - Yong Yin
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
- *Correspondence: Yong Yin, ; Changsheng Ma,
| | - Changsheng Ma
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
- *Correspondence: Yong Yin, ; Changsheng Ma,
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23
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Ju SG, Ahn YC, Kim YB, Kim JM, Kwon DY, Park BS, Yang K. Dosimetric comparison between VMAT plans using the fast-rotating O-ring linac with dual-layer stacked MLC and helical tomotherapy for nasopharyngeal carcinoma. Radiat Oncol 2022; 17:155. [PMID: 36096874 PMCID: PMC9465858 DOI: 10.1186/s13014-022-02124-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2022] [Accepted: 08/30/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND To compare the dosimetric profiles of volumetric modulated arc therapy (VMAT) plans using the fast-rotating O-ring linac (the Halcyon system) based on a dual-layer stacked multi-leaf collimator and helical tomotherapy (HT) for nasopharyngeal cancer (NPCa). METHODS For 30 NPCa patients, three sets of RT plans were generated, under the same policy of contouring and dose constraints: HT plan; Halcyon VMAT plan with two arcs (HL2arc); and Halcyon VMAT plan with four arcs (HL4arc), respectively. The intended dose schedule was to deliver 67.2 Gy to the planning gross target volume (P-GTV) and 56.0 Gy to the planning clinical target volume (P-CTV) in 28 fractions using the simultaneously integrated boost concept. Target volumes and organ at risks dose metrics were evaluated for all plans. Normal tissue complication probabilities (NTCP) for esophagus, parotid glands, spinal cord, and brain stem were compared. RESULTS The HT plan achieved the best dose homogeneity index for both P_GTV and P_CTV, followed by the HL4arc and L2arc plans. No significant difference in the dose conformity index (CI) for P_GTV was observed between the HT plan (0.80) and either the HL2arc plan (0.79) or the HL4arc plan (0.83). The HL4arc plan showed the best CI for P_CTV (0.88), followed by the HL2arc plan (0.83) and the HT plan (0.80). The HL4arc plan (median, interquartile rage (Q1, Q3): 25.36 (22.22, 26.89) Gy) showed the lowest Dmean in the parotid glands, followed by the HT (25.88 (23.87, 27.87) Gy) and HL2arc plans (28.00 (23.24, 33.99) Gy). In the oral cavity (OC) dose comparison, the HT (22.03 (19.79, 24.85) Gy) plan showed the lowest Dmean compared to the HL2arc (23.96 (20.84, 28.02) Gy) and HL4arc (24.14 (20.17, 27.53) Gy) plans. Intermediate and low dose regions (40-65% of the prescribed dose) were well fit to the target volume in HL4arc, compared to the HT and HL2arc plans. All plans met the dose constraints for the other OARs with sufficient dose margins. The between-group differences in the median NTCP values for the parotid glands and OC were < 3.47% and < 1.7% points, respectively. CONCLUSIONS The dosimetric profiles of Halcyon VMAT plans were comparable to that of HT, and HL4arc showed better dosimetric profiles than HL2arc for NPCa.
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Affiliation(s)
- Sang Gyu Ju
- Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Irwon-Ro 81, Gangnam-Gu, Seoul, 06351, Republic of Korea
| | - Yong Chan Ahn
- Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Irwon-Ro 81, Gangnam-Gu, Seoul, 06351, Republic of Korea.
| | - Yeong-Bi Kim
- Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Irwon-Ro 81, Gangnam-Gu, Seoul, 06351, Republic of Korea
| | - Jin Man Kim
- Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Irwon-Ro 81, Gangnam-Gu, Seoul, 06351, Republic of Korea
| | - Dong Yeol Kwon
- Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Irwon-Ro 81, Gangnam-Gu, Seoul, 06351, Republic of Korea
| | - Byoung Suk Park
- Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Irwon-Ro 81, Gangnam-Gu, Seoul, 06351, Republic of Korea
| | - Kyungmi Yang
- Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Irwon-Ro 81, Gangnam-Gu, Seoul, 06351, Republic of Korea
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24
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Hammers J, Lindsay D, Narayanasamy G, Sud S, Tan X, Dooley J, Marks LB, Chen RC, Das SK, Mavroidis P. Evaluation of the clinical impact of the differences between planned and delivered dose in prostate cancer radiotherapy based on CT-on-rails IGRT and patient-reported outcome scores. J Appl Clin Med Phys 2022; 24:e13780. [PMID: 36087039 PMCID: PMC9859987 DOI: 10.1002/acm2.13780] [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: 03/15/2022] [Revised: 06/10/2022] [Accepted: 07/18/2022] [Indexed: 01/26/2023] Open
Abstract
PURPOSE To estimate the clinical impact of differences between delivered and planned dose using dose metrics and normal tissue complication probability (NTCP) modeling. METHODS Forty-six consecutive patients with prostate adenocarcinoma between 2010 and 2015 treated with intensity-modulated radiation therapy (IMRT) and who had undergone computed tomography on rails imaging were included. Delivered doses to bladder and rectum were estimated using a contour-based deformable image registration method. The bladder and rectum NTCP were calculated using dose-response parameters applied to planned and delivered dose distributions. Seven urinary and gastrointestinal symptoms were prospectively collected using the validated prostate cancer symptom indices patient reported outcome (PRO) at pre-treatment, weekly treatment, and post-treatment follow-up visits. Correlations between planned and delivered doses against PRO were evaluated in this study. RESULTS Planned mean doses to bladder and rectum were 44.9 ± 13.6 Gy and 42.8 ± 7.3 Gy, while delivered doses were 46.1 ± 13.4 Gy and 41.3 ± 8.7 Gy, respectively. D10cc for rectum was 64.1 ± 7.6 Gy for planned and 60.1 ± 9.3 Gy for delivered doses. NTCP values of treatment plan were 22.3% ± 8.4% and 12.6% ± 5.9%, while those for delivered doses were 23.2% ± 8.4% and 9.9% ± 8.3% for bladder and rectum, respectively. Seven of 25 patients with follow-up data showed urinary complications (28%) and three had rectal complications (12%). Correlations of NTCP values of planned and delivered doses with PRO follow-up data were random for bladder and moderate for rectum (0.68 and 0.67, respectively). CONCLUSION Sensitivity of bladder to clinical variations of dose accumulation indicates that an automated solution based on a DIR that considers inter-fractional organ deformation could recommend intervention. This is intended to achieve additional rectum sparing in cases that indicate higher than expected dose accumulation early during patient treatment in order to prevent acute severity of bowel symptoms.
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Affiliation(s)
- Jacob Hammers
- Department of Radiation OncologyUniversity of North Carolina at Chapel HillNorth CarolinaUSA
| | - Daniel Lindsay
- Department of Radiation OncologyUniversity of North Carolina at Chapel HillNorth CarolinaUSA
| | - Ganesh Narayanasamy
- Department of Radiation OncologyUniversity of Arkansas for Medical SciencesArkansasUSA
| | - Shivani Sud
- Department of Radiation OncologyUniversity of North Carolina at Chapel HillNorth CarolinaUSA
| | - Xianming Tan
- Lineberger Comprehensive Cancer CenterUniversity of North Carolina HospitalsChapel HillNorth CarolinaUSA
| | - John Dooley
- Department of Radiation OncologyUniversity of North Carolina at Chapel HillNorth CarolinaUSA
| | - Lawrence B. Marks
- Department of Radiation OncologyUniversity of North Carolina at Chapel HillNorth CarolinaUSA
| | - Ronald C. Chen
- Department of Radiation OncologyUniversity of North Carolina at Chapel HillNorth CarolinaUSA
| | - Shiva K. Das
- Department of Radiation OncologyUniversity of North Carolina at Chapel HillNorth CarolinaUSA
| | - Panayiotis Mavroidis
- Department of Radiation OncologyUniversity of North Carolina at Chapel HillNorth CarolinaUSA
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Kang SW, Kang S, Lee B, Song C, Eom KY, Jang BS, Kim IA, Kim JS, Cho W, Shin DS, Kim JY, Chung JB. Evaluation of the dosimetric and radiobiological parameters in four radiotherapy regimens for synchronous bilateral breast cancer. J Appl Clin Med Phys 2022; 23:e13706. [PMID: 35727562 PMCID: PMC9359036 DOI: 10.1002/acm2.13706] [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: 10/21/2021] [Revised: 05/18/2022] [Accepted: 06/04/2022] [Indexed: 11/25/2022] Open
Abstract
This study is to investigate the optimal treatment option for synchronous bilateral breast cancer (SBBC) by comparing dosimetric and radiobiological parameters of intensity‐modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) plans using single and dual isocenters. Twenty patients with SBBC without lymph node involvement were selected retrospectively. Four treatment plans were generated for each patient using the Eclipse treatment planning system (Varian Medical System, Palo Alto, CA, USA) following two delivery techniques with two isocenter conditions—IMRT using a single isocenter (IMRT_Iso1), VMAT using a single isocenter (VMAT_Iso1), IMRT using dual isocenters (IMRT_Iso2), and VMAT using dual isocenters (VMAT_Iso2). A dose of 42.56 Gy in 16 fractions was prescribed for the planning target volume (PTV). All plans were calculated using the Acuros XB algorithm and a photon optimizer for a 6‐MV beam of a Vital Beam linear accelerator. PTV‐related dosimetric parameters were analyzed. Further, the homogeneity index, conformity index, and conformation number were computed to evaluate plan quality. Dosimetric parameters were also measured for the organs at risk (OARs). In addition, the equivalent uniform dose corresponding to an equivalent dose related to a reference of 2 Gy per fraction, the tumor control probability, and the normal tissue complication probability were calculated based on the dose–volume histogram to investigate the radiobiological impact on PTV and OARs. IMRT_Iso1 exhibited similar target coverage and a certain degree of dosimetric improvement in OAR sparing compared to the other techniques. It also exhibited some radiobiological improvement, albeit insignificant. Although IMRT_Iso1 significantly increased monitor unit compared to VMAT_Iso1, which is the best option in terms of delivery efficiency, there was only a 22% increase in delivery time. Therefore, in conclusion, IMRT_Iso1, the complete treatment of which can be completed using a single setup, is the most effective method for treating SBBC.
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Affiliation(s)
- Sang-Won Kang
- Department of Radiation Oncology, Seoul National University Bundang Hospital, Seongnam-si, Gyeonggi-do, Republic of Korea
| | - Seonghee Kang
- Department of Radiation Oncology, Seoul National University Hospital, Seoul, Republic of Korea
| | - Boram Lee
- Department of Radiation Oncology, Seoul National University Bundang Hospital, Seongnam-si, Gyeonggi-do, Republic of Korea
| | - Changhoon Song
- Department of Radiation Oncology, Seoul National University Bundang Hospital, Seongnam-si, Gyeonggi-do, Republic of Korea
| | - Keun-Yong Eom
- Department of Radiation Oncology, Seoul National University Bundang Hospital, Seongnam-si, Gyeonggi-do, Republic of Korea
| | - Bum-Sup Jang
- Department of Radiation Oncology, Seoul National University Bundang Hospital, Seongnam-si, Gyeonggi-do, Republic of Korea
| | - In Ah Kim
- Department of Radiation Oncology, Seoul National University Bundang Hospital, Seongnam-si, Gyeonggi-do, Republic of Korea
| | - Jae-Sung Kim
- Department of Radiation Oncology, Seoul National University Bundang Hospital, Seongnam-si, Gyeonggi-do, Republic of Korea
| | - Woong Cho
- Department of Radiation Oncology, Seoul National University Boramae Medical Center, Seoul, Republic of Korea
| | - Dong-Suk Shin
- Proton Therapy Center, National Cancer Center, Goyang-si, Gyeonggi-do, Republic of Korea
| | - Jin-Young Kim
- Departments of Radiation Oncology, Dongnam Institute of Radiological and Medical Sciences, Busan, Republic of Korea
| | - Jin-Beom Chung
- Department of Radiation Oncology, Seoul National University Bundang Hospital, Seongnam-si, Gyeonggi-do, Republic of Korea
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Chen M, Wang Z, Jiang S, Sun J, Wang L, Sahoo N, Brandon Gunn G, Frank SJ, Xu C, Chen J, Nguyen QN, Chang JY, Liao Z, Ronald Zhu X, Zhang X. Predictive performance of different NTCP techniques for radiation-induced esophagitis in NSCLC patients receiving proton radiotherapy. Sci Rep 2022; 12:9178. [PMID: 35655073 PMCID: PMC9163134 DOI: 10.1038/s41598-022-12898-8] [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: 08/30/2021] [Accepted: 05/18/2022] [Indexed: 11/24/2022] Open
Abstract
This study aimed to compare the predictive performance of different modeling methods in developing normal tissue complication probability (NTCP) models for predicting radiation-induced esophagitis (RE) in non–small cell lung cancer (NSCLC) patients receiving proton radiotherapy. The dataset was composed of 328 NSCLC patients receiving passive-scattering proton therapy and 41.6% of the patients experienced ≥ grade 2 RE. Five modeling methods were used to build NTCP models: standard Lyman–Kutcher–Burman (sLKB), generalized LKB (gLKB), multivariable logistic regression using two variable selection procedures-stepwise forward selection (Stepwise-MLR), and least absolute shrinkage and selection operator (LASSO-MLR), and support vector machines (SVM). Predictive performance was internally validated by a bootstrap approach for each modeling method. The overall performance, discriminative ability, and calibration were assessed using the Negelkerke R2, area under the receiver operator curve (AUC), and Hosmer–Lemeshow test, respectively. The LASSO-MLR model showed the best discriminative ability with an AUC value of 0.799 (95% confidence interval (CI): 0.763–0.854), and the best overall performance with a Negelkerke R2 value of 0.332 (95% CI: 0.266–0.486). Both of the optimism-corrected Negelkerke R2 values of the SVM and sLKB models were 0.301. The optimism-corrected AUC of the gLKB model (0.796) was higher than that of the SVM model (0.784). The sLKB model had the smallest optimism in the model variation and discriminative ability. In the context of classification and probability estimation for predicting the NTCP for radiation-induced esophagitis, the MLR model developed with LASSO provided the best predictive results. The simplest LKB modeling had similar or even better predictive performance than the most complex SVM modeling, and it was least likely to overfit the training data. The advanced machine learning approach might have limited applicability in clinical settings with a relatively small amount of data.
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Affiliation(s)
- Mei Chen
- Department of Radiation Oncology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.,Department of Radiation Physics, Unit 1150, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA
| | - Zeming Wang
- Department of Radiation Physics, Unit 1150, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA
| | - Shengpeng Jiang
- Department of Radiation Physics, Unit 1150, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA.,Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 30060, China
| | - Jian Sun
- Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 30060, China.,Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA
| | - Li Wang
- Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA
| | - Narayan Sahoo
- Department of Radiation Physics, Unit 1150, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA
| | - G Brandon Gunn
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA
| | - Steven J Frank
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA
| | - Cheng Xu
- Department of Radiation Oncology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
| | - Jiayi Chen
- Department of Radiation Oncology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
| | - Quynh-Nhu Nguyen
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA
| | - Joe Y Chang
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA
| | - Zhongxing Liao
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA
| | - X Ronald Zhu
- Department of Radiation Physics, Unit 1150, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA
| | - Xiaodong Zhang
- Department of Radiation Physics, Unit 1150, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA.
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Chang S, Liu G, Zhao L, Zheng W, Yan D, Chen P, Li X, Yang K, Deraniyagala R, Stevens C, Grills I, Chinnaiyan P, Li X, Ding X. Redefine the Role of Spot-Scanning Proton Beam Therapy for the Single Brain Metastasis Stereotactic Radiosurgery. Front Oncol 2022; 12:804036. [PMID: 35664795 PMCID: PMC9160604 DOI: 10.3389/fonc.2022.804036] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2021] [Accepted: 04/14/2022] [Indexed: 12/30/2022] Open
Abstract
Purpose To explore the role of using Pencil Beam Scanning (PBS) proton beam therapy in single lesion brain stereotactic radiosurgery (SRS), we developed and validated a dosimetric in silico model to assist in the selection of an optimal treatment approach among the conventional Volumetric Modulated Arc Therapy (VMAT), Intensity Modulated Proton Therapy (IMPT) and Spot-scanning Proton Arc (SPArc). Material and Methods A patient’s head CT data set was used as an in silico model. A series of targets (volume range from 0.3 cc to 33.03 cc) were inserted in the deep central and peripheral region, simulating targets with different sizes and locations. Three planning groups: IMPT, VMAT, and SPArc were created for dosimetric comparison purposes and a decision tree was built based on this in silico model. Nine patients with single brain metastases were retrospectively selected for validation. Multiple dosimetric metrics were analyzed to assess the plan quality, such as dose Conformity Index (CI) (ratio of the target volume to 100% prescription isodose volume); R50 (ratio of 50% prescription isodose volume to the target volume); V12Gy (volume of brain tissue minus GTV receiving 12 Gy), and mean dose of the normal brain. Normal tissue complication probability (NTCP) of brain radionecrosis (RN) was calculated using the Lyman-Kutcher-Burman (LKB) model and total treatment delivery time was calculated. Six physicians from different institutions participated in the blind survey to evaluate the plan quality and rank their choices. Results The study showed that SPArc has a dosimetric advantage in the V12Gy and R50 with target volumes > 9.00 cc compared to VMAT and IMPT. A significant clinical benefit can be found in deep centrally located lesions larger than 20.00 cc using SPArc because of the superior dose conformity and mean dose reduction in healthy brain tissue. Nine retrospective clinical cases and the blind survey showed good agreement with the in silico dosimetric model and decision tree. Additionally, SPArc significantly reduced the treatment delivery time compared to VMAT (SPArc 184.46 ± 59.51s vs. VMAT: 1574.78 ± 213.65s). Conclusion The study demonstrated the feasibility of using Proton beam therapy for single brain metastasis patients utilizing the SPArc technique. At the current stage of technological development, VMAT remains the current standard modality of choice for single lesion brain SRS. The in silico dosimetric model and decision tree presented here could be used as a practical clinical decision tool to assist the selection of the optimal treatment modality among VMAT, IMPT, and SPArc in centers that have both photon and proton capabilities.
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Affiliation(s)
- Sheng Chang
- Department of Radiation Oncology, Renmin Hospital, Wuhan University, Wuhan, China
- Department of Radiation Oncology, Beaumont Health System, Royal Oak, MI, United States
| | - Gang Liu
- Department of Radiation Oncology, Beaumont Health System, Royal Oak, MI, United States
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Lewei Zhao
- Department of Radiation Oncology, Beaumont Health System, Royal Oak, MI, United States
| | - Weili Zheng
- Department of Radiation Oncology, Beaumont Health System, Royal Oak, MI, United States
| | - Di Yan
- Department of Radiation Oncology, Beaumont Health System, Royal Oak, MI, United States
| | - Peter Chen
- Department of Radiation Oncology, Beaumont Health System, Royal Oak, MI, United States
| | - Xiangpan Li
- Department of Radiation Oncology, Renmin Hospital, Wuhan University, Wuhan, China
| | - Kunyu Yang
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Rohan Deraniyagala
- Department of Radiation Oncology, Beaumont Health System, Royal Oak, MI, United States
| | - Craig Stevens
- Department of Radiation Oncology, Beaumont Health System, Royal Oak, MI, United States
| | - Inga Grills
- Department of Radiation Oncology, Beaumont Health System, Royal Oak, MI, United States
| | - Prakash Chinnaiyan
- Department of Radiation Oncology, Beaumont Health System, Royal Oak, MI, United States
| | - Xiaoqiang Li
- Department of Radiation Oncology, Beaumont Health System, Royal Oak, MI, United States
| | - Xuanfeng Ding
- Department of Radiation Oncology, Beaumont Health System, Royal Oak, MI, United States
- *Correspondence: Xuanfeng Ding,
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Yusufaly TI. Extending the relative seriality formalism for interpretable deep learning of normal tissue complication probability models. MACHINE LEARNING: SCIENCE AND TECHNOLOGY 2022. [DOI: 10.1088/2632-2153/ac6932] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022] Open
Abstract
Abstract
We formally demonstrate that the relative seriality (RS) model of normal tissue complication probability (NTCP) can be recast as a simple neural network with one convolutional and one pooling layer. This approach enables us to systematically construct deep relative seriality networks (DRSNs), a new class of mechanistic generalizations of the RS model with radiobiologically interpretable parameters amenable to deep learning. To demonstrate the utility of this formulation, we analyze a simplified example of xerostomia due to irradiation of the parotid gland during alpha radiopharmaceutical therapy. Using a combination of analytical calculations and numerical simulations, we show for both the RS and DRSN cases that the ability of the neural network to generalize without overfitting is tied to ‘stiff’ and ‘sloppy’ directions in the parameter space of the mechanistic model. These results serve as proof-of-concept for radiobiologically interpretable deep learning of NTCP, while simultaneously yielding insight into how such techniques can robustly generalize beyond the training set despite uncertainty in individual parameters.
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Blake SW. Can dose convolution modelling explain bath and shower effects in rat spinal cord? Phys Med Biol 2022; 67. [DOI: 10.1088/1361-6560/ac5c8e] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2021] [Accepted: 03/10/2022] [Indexed: 12/24/2022]
Abstract
Abstract
Objective. ‘Bath and shower’ effects were first seen in proton irradiations of rat spinal cord, where a low dose ‘bath’ reduced the smaller field ‘shower’ dose needed for limb paralysis giving the appearance of sensitisation of the cord or disproportionate response. This was difficult to reconcile with existing tissue complication models. The purpose of this investigation is to explore a different approach using a dose convolution algorithm to model the 50% isoeffect endpoint. Approach. Bath and shower dose distributions were convolved with Gaussian functions with widths specified by the σ parameter. The hypothesis was that the maximum value from the convolved distributions was constant for isoeffect across the modelled scenarios. A simpler field length dependent relative biological effectiveness (FLRBE) approach was also used for a subset of the data which gave results independent of σ. Main results. The maximum values from the convolved distributions were constant within ±17% across the bath and shower experiments for σ = 3.5 mm, whereas the maximum dose varied by a factor of four. The FLRBE results were also within ±14% confirming the validity of the dose convolution approach. Significance. A simple approach using dose convolution modelling of the 50% isotoxicity gave compelling consistency with the full range of bath and shower results, while the FLRBE approach confirmed the results for the symmetric field data. Convolution modelling and the effect of time interval were consistent with a signalling factor diffusion mechanism such as the ‘bystander effect’. The results suggest biological effectiveness is reduced for very small field sizes, requiring a higher isoeffect dose. By implication, the bath dose does not sensitise the cord to the shower dose; when biological effectiveness is accounted for, a small increase in the bath dose requires a significantly larger reduction in shower dose for isoeffect.
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Szalkowski G, Karakas Z, Cengiz M, Schreiber E, Das S, Yazici G, Ozyigit G, Mavroidis P. Stereotactic body radiotherapy optimization to reduce the risk of carotid blowout syndrome using normal tissue complication probability objectives. J Appl Clin Med Phys 2022; 23:e13563. [PMID: 35194924 PMCID: PMC9121056 DOI: 10.1002/acm2.13563] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2021] [Revised: 01/14/2022] [Accepted: 02/02/2022] [Indexed: 12/24/2022] Open
Abstract
PURPOSE To determine the possibility of further improving clinical stereotactic body radiotherapy (SBRT) plans using normal tissue complication probability (NTCP) objectives in order to minimize the risk for carotid blowout syndrome (CBOS). METHODS 10 patients with inoperable locally recurrent head and neck cancer, who underwent SBRT using CyberKnife were analyzed. For each patient, three treatment plans were examined: (1) cone-based without delineation of the ipsilateral internal carotid (clinical plan used to treat the patients); (2) cone-based with the carotid retrospectively delineated and spared; and (3) Iris-based with carotid sparing. The dose-volume histograms of the target and primary organs at risk were calculated. The three sets of plans were compared based on dosimetric and TCP/NTCP (tumor control and normal tissue complication probabilities) metrics. For the NTCP values of carotid, the relative seriality model was used with the following parameters: D50 = 40 Gy, γ = 0.75, and s = 1.0. RESULTS Across the 10 patient plans, the average TCP did not significantly change when the plans were re-optimized to spare the carotid. The estimated risk of CBOS was significantly decreased in the re-optimized plans, by 14.9% ± 7.4% for the cone-based plans and 17.7% ± 7.1% for the iris-based plans (p = 0.002 for both). The iris-based plans had significant (p = 0.02) reduced CBOS risk and delivery time (20.1% ± 7.4% time reduction, p = 0.002) compared to the cone-based plans. CONCLUSION A significant improvement in the quality of the clinical plans could be achieved through the delineation of the internal carotids and the use of more modern treatment delivery modalities. In this way, for the same target coverage, a significant reduction in the risk of CBOS could be achieved. The range of risk reduction varied depending on the proximity of carotid artery to the target.
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Affiliation(s)
- Gregory Szalkowski
- Department of Radiation OncologyUniversity of North CarolinaNorth CarolinaChapel HillUSA
| | - Zeynep Karakas
- Department of Radiation OncologyUniversity of North CarolinaNorth CarolinaChapel HillUSA
| | - Mustafa Cengiz
- Faculty of MedicineDepartment of Radiation OncologyHacettepe UniversitySihhiyeAnkaraTurkey
| | - Eric Schreiber
- Department of Radiation OncologyUniversity of North CarolinaNorth CarolinaChapel HillUSA
| | - Shiva Das
- Department of Radiation OncologyUniversity of North CarolinaNorth CarolinaChapel HillUSA
| | - Gozde Yazici
- Faculty of MedicineDepartment of Radiation OncologyHacettepe UniversitySihhiyeAnkaraTurkey
| | - Gokhan Ozyigit
- Faculty of MedicineDepartment of Radiation OncologyHacettepe UniversitySihhiyeAnkaraTurkey
| | - Panayiotis Mavroidis
- Department of Radiation OncologyUniversity of North CarolinaNorth CarolinaChapel HillUSA
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Haghbin A, Mostaar A, Paydar R, Bakhshandeh M, Nikoofar A, Houshyari M, Cheraghi S. Prediction of chronic kidney disease in abdominal cancers radiation therapy using the functional assays of normal tissue complication probability models. J Cancer Res Ther 2022; 18:718-724. [PMID: 35900545 DOI: 10.4103/jcrt.jcrt_179_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
Aim The purpose of this study is to predict chronic kidney disease (CKD) in the radiotherapy of abdominal cancers by evaluating clinical and functional assays of normal tissue complication probability (NTCP) models. Materials and Methods Radiation renal damage was analyzed in 50 patients with abdominal cancers 12 months after radiotherapy through a clinical estimated glomerular filtration rate (eGFR). According to the common terminology criteria for the scoring system of adverse events, Grade 2 CKD (eGFR ≤30-59 ml/min/1.73 m2) was considered as the radiation therapy endpoint. Modeling and parameter estimation of NTCP models were performed for the Lyman-equivalent uniform dose (EUD), the logit-EUD critical volume (CV), the relative seriality, and the mean dose model. Results The confidence interval of the fitted parameters was 95%. The parameter value of D50 was obtained 22-38 Gy, and the n and s parameters were equivalent to 0.006 -3 and 1, respectively. According to the Akaike's information criterion, the mean dose model predicts radiation-induced CKD more accurately than the other models. Conclusion Although the renal medulla consists of many nephrons arranged in parallel, each nephron has a seriality architecture as renal functional subunits. Therefore, based on this principle and modeling results in this study, the whole kidney organs may have a serial-parallel combination or a secret architecture.
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Affiliation(s)
- Ameneh Haghbin
- Department of Radiation Sciences, Faculty of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Ahmad Mostaar
- Department of Medical Physics and Biomedical Engineering, Shahid Beheshti University of Medical, Tehran, Iran
| | - Reza Paydar
- Department of Radiation Sciences, Faculty of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Mohsen Bakhshandeh
- Department of Radiology Technology, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Alireza Nikoofar
- Department of Radiation Oncology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Mohammad Houshyari
- Department of Radiation Oncology, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Susan Cheraghi
- Department of Radiation Sciences, Faculty of Allied Medicine, Iran University of Medical Sciences; Radiation Biology Research Center, Iran University of Medical Sciences, Tehran, Iran
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Das Majumdar SK, Amritt A, Dhar SS, Barik S, Beura SS, Mishra T, Muduly DK, Dash A, Parida DK. A Dosimetric Study Comparing 3D-CRT vs. IMRT vs. VMAT in Left-Sided Breast Cancer Patients After Mastectomy at a Tertiary Care Centre in Eastern India. Cureus 2022; 14:e23568. [PMID: 35494897 PMCID: PMC9045011 DOI: 10.7759/cureus.23568] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/28/2022] [Indexed: 11/08/2022] Open
Abstract
Introduction Post-mastectomy radiation in left-sided breast cancer in women continues to pose a significant risk to the underlying lungs and heart. This study analyzed the difference in planning target volume (PTV) coverage and dose to the organs at risk (OAR) by using three different planning methods for the same patient - three-dimensional conformal radiotherapy (3D-CRT), intensity-modulated radiotherapy (IMRT), and volumetric-modulated arc therapy (VMAT). Material and methods Thirty-five left-sided breast cancer patients' post-mastectomy were included in this study, and three different plans for adjuvant radiation were created using 3D-CRT, IMRT, and VMAT. The prescribed dose was 50Gy in 25 fractions. Kruskal-Wallis analysis of variance (ANOVA) was done, followed by a pairwise t-test to establish a hierarchy of plan quality and dosimetric benefits. The plans were compared with PTV95, homogeneity index (HI), conformity index (CI), hotspot (V107%), left lung V20Gy, mean lung dose, heart V25Gy, mean heart dose, and integral dose (ID) to the body. Results Both VMAT and IMRT led to improved PTV95% coverage (95.63±1.82%, p=0.000 in VMAT; 93.70±2.16 %, p=0.000; 81.40±6.27% in 3D-CRT arm) and improved CI (0.91±0.06 in IMRT [p<0.05] and 0.96±0.02 for VMAT plans [p<0.05]) as compared to 3D-CRT (0.66±0.11), which was statistically significant on pairwise analysis. In contrast, the difference in HI and reduction in hotspots were not significantly different. Left lung V20 was statistically very different between the three arms with the highest values in IMRT (36.64±4.45) followed by 3D-CRT (34.80±2.24) and the most negligible value in VMAT (33.03±4.20). Mean lung dose was also statistically different between the three arms. There was a statistically significant difference in mean heart dose between the three arms on pairwise analysis. Both the inverse planning methods led to a statistically significant increase in low dose volume (V5 and V10) of the ipsilateral lung, opposite lung, and heart, and increased ID to the body excluding the PTV. Conclusion While both the inverse planning modalities led to increased coverage, better CI, and better HI and decreased high dose volumes in OARs, there was increased low volume irradiation of heart, lungs, and body with VMAT faring marginally better than IMRT in coverage and decreasing lung irradiation with comparable heart irradiation.
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Affiliation(s)
| | - Adhar Amritt
- Radiation Oncology, All India Institute of Medical Sciences, Bhubaneswar, Bhubaneswar, IND
| | - Sovan Sarang Dhar
- Radiation Oncology, All India Institute of Medical Sciences, Bhubaneswar, Bhubaneswar, IND
| | - Sandip Barik
- Radiation Oncology, All India Institute of Medical Sciences, Bhubaneswar, Bhubaneswar, IND
| | - Sasanka S Beura
- Medical Physics, All India Institute of Medical Sciences, Bhubaneswar, Bhubaneswar, IND
| | - Tushar Mishra
- Surgery, All India Institute of Medical Sciences, Bhubaneswar, Bhubaneswar, IND
| | - Dillip K Muduly
- Surgical Oncology, All India Institute of Medical Sciences, Bhubaneswar, Bhubaneswar, IND
| | - Ashish Dash
- Pharmacology, All India Institute of Medical Sciences, Bhubaneswar, Bhubaneswar, IND
| | - Dillip Kumar Parida
- Radiation Oncology, All India Institute of Medical Sciences, Bhubaneswar, Bhubaneswar, IND
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MRI-Based Radiotherapy Planning to Reduce Rectal Dose in Excess of Tolerance. Prostate Cancer 2022; 2022:7930744. [PMID: 35154830 PMCID: PMC8831048 DOI: 10.1155/2022/7930744] [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: 07/18/2021] [Revised: 12/15/2021] [Accepted: 12/28/2021] [Indexed: 11/18/2022] Open
Abstract
Materials and Methods This prospective single-arm study enrolled 15 men treated with IG-IMRT for localized prostate cancer. All participants received a dedicated 3 Tesla MRI examination of the prostate in addition to a pelvic CT examination for treatment planning. Two volumetric modulated arc therapy (VMAT) plans with a prescription dose of 79.2 Gy were designed using identical constraints based on CT- and MRI-defined consensus volumes. The volume of rectum exposed to 70 Gy or more was compared using the Wilcoxon paired signed rank test. Results For CT-based treatment plans, the median volume of rectum receiving 70 Gy or more was 9.3 cubic centimeters (cc) (IQR 7.0 to 10.2) compared with 4.9 cc (IQR 4.1 to 7.8) for MRI-based plans. This resulted in a median volume reduction of 2.1 cc (IQR 0.5 to 5.3, P < .001). Conclusions Using MRI to plan prostate IG-IMRT to a dose of 79.2 Gy reduces the volume of rectum receiving radiation dose in excess of tolerance (70 Gy or more) and should be considered in men who are at high risk for late rectal toxicity and are not good candidates for other rectal sparing techniques such as hydrogel spacer. This trial is registered with NCT02470910.
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Du QH, Li J, Gan YX, Zhu HJ, Yue HY, Li XD, Ou X, Zhong QL, Luo DJ, Xie YT, Liang QF, Wang RS, Liu WQ. Potential Defects and Improvements of Equivalent Uniform Dose Prediction Model Based on the Analysis of Radiation-Induced Brain Injury. Front Oncol 2022; 11:743941. [PMID: 35087743 PMCID: PMC8786722 DOI: 10.3389/fonc.2021.743941] [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: 07/20/2021] [Accepted: 12/13/2021] [Indexed: 11/13/2022] Open
Abstract
PURPOSE To study the impact of dose distribution on volume-effect parameter and predictive ability of equivalent uniform dose (EUD) model, and to explore the improvements. METHODS AND MATERIALS The brains of 103 nasopharyngeal carcinoma patients treated with IMRT were segmented according to dose distribution (brain and left/right half-brain for similar distributions but different sizes; V D with different D for different distributions). Predictive ability of EUDV D (EUD of V D ) for radiation-induced brain injury was assessed by receiver operating characteristics curve (ROC) and area under the curve (AUC). The optimal volume-effect parameter a of EUD was selected when AUC was maximal (mAUC). Correlations between mAUC, a and D were analyzed by Pearson correlation analysis. Both mAUC and a in brain and half-brain were compared by using paired samples t-tests. The optimal D V and V D points were selected for a simple comparison. RESULTS The mAUC of brain/half-brain EUD was 0.819/0.821 and the optimal a value was 21.5/22. When D increased, mAUC of EUDV D increased, while a decreased. The mAUC reached the maximum value when D was 50-55 Gy, and a was always 1 when D ≥55 Gy. The difference of mAUC/a between brain and half-brain was not significant. If a was in range of 1 to 22, AUC of brain/half-brain EUDV55 Gy (0.857-0.830/0.845-0.830) was always larger than that of brain/half-brain EUD (0.681-0.819/0.691-0.821). The AUCs of optimal dose/volume points were 0.801 (brain D2.5 cc), 0.823 (brain V70 Gy), 0.818 (half-brain D1 cc), and 0.827 (half-brain V69 Gy), respectively. Mean dose (equal to EUDV D with a = 1) of high-dose volume (V50 Gy-V60 Gy) was superior to traditional EUD and dose/volume points. CONCLUSION Volume-effect parameter of EUD is variable and related to dose distribution. EUD with large low-dose volume may not be better than simple dose/volume points. Critical-dose-volume EUD could improve the predictive ability and has an invariant volume-effect parameter. Mean dose may be the case in which critical-dose-volume EUD has the best predictive ability.
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Affiliation(s)
- Qing-Hua Du
- Department of Radiation Oncology, Second Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Jian Li
- Department of Radiation Oncology, Second Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Yi-Xiu Gan
- Department of Radiation Oncology, Second Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Hui-Jun Zhu
- Department of Radiation Oncology, Second Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Hai-Ying Yue
- Department of Radiation Oncology, Second Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Xiang-De Li
- Department of Radiation Oncology, Second Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Xue Ou
- Department of Radiation Oncology, Second Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Qiu-Lu Zhong
- Department of Radiation Oncology, Second Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Dan-Jing Luo
- Department of Radiation Oncology, Second Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Yi-Ting Xie
- Department of Radiation Oncology, Second Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Qian-Fu Liang
- Department of Radiation Oncology, Second Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Ren-Sheng Wang
- Department of Radiation Oncology, First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Wen-Qi Liu
- Department of Radiation Oncology, Second Affiliated Hospital of Guangxi Medical University, Nanning, China
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Dell'Oro M, Wilson P, Short M, Hua CH, Merchant TE, Bezak E. Normal tissue complication probability modeling to guide individual treatment planning in pediatric cranial proton and photon radiotherapy. Med Phys 2021; 49:742-755. [PMID: 34796509 DOI: 10.1002/mp.15360] [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: 07/05/2021] [Revised: 11/05/2021] [Accepted: 11/09/2021] [Indexed: 11/10/2022] Open
Abstract
PURPOSE Proton therapy (PT) is broadly accepted as the gold standard of care for pediatric patients with cranial cancer. The superior dose distribution of PT compared to photon radiotherapy reduces normal tissue complication probability (NTCP) for organs at risk. As NTCPs for pediatric organs are not well understood, clinics generally base radiation response on adult data. However, there is evidence that radiation response strongly depends on the age and even sex of a patient. Furthermore, questions surround the influence of individual intrinsic radiosensitivity (α/β ratio) on pediatric NTCP. While the clinical pediatric NTCP data is scarce, radiobiological modeling and sensitivity analyses can be used to investigate the NTCP trends and its dependence on individual modeling parameters. The purpose of this study was to perform sensitivity analyses of NTCP models to ascertain the dependence of radiosensitivity, sex, and age of a child and predict cranial side-effects following intensity-modulated proton therapy (IMPT) and intensity-modulated radiotherapy (IMRT). METHODS Previously, six sex-matched pediatric cranial datasets (5, 9, and 13 years old) were planned in Varian Eclipse treatment planning system (13.7). Up to 108 scanning beam IMPT plans and 108 IMRT plans were retrospectively optimized for a range of simulated target volumes and locations. In this work, dose-volume histograms were extracted and imported into BioSuite Software for radiobiological modeling. Relative-Seriality and Lyman-Kutcher-Burman models were used to calculate NTCP values for toxicity endpoints, where TD50, (based on reported adult clinical data) was varied to simulate sex dependence of NTCP. Plausible parameter ranges, based on published literature for adults, were used in modeling. In addition to sensitivity analyses, a 20% difference in TD50 was used to represent the radiosensitivity between the sexes (with females considered more radiosensitive) for ease of data comparison as a function of parameters such as α/β ratio. RESULTS IMPT plans resulted in lower NTCP compared to IMRT across all models (p < 0.0001). For medulloblastoma treatment, the risk of brainstem necrosis (> 10%) and cochlea tinnitus (> 20%) among females could potentially be underestimated considering a lower TD50 value for females. Sensitivity analyses show that the difference in NTCP between sexes was significant (p < 0.0001). Similarly, both brainstem necrosis and cochlea tinnitus NTCP varied significantly (p < 0.0001) across tested α/β as a function of TD50 values (assumption being that TD50 values are 20% lower in females). If the true α/β of these pediatric tissues is higher than expected (α/β ∼ 3), the risk of tinnitus for IMRT can significantly increase (p < 0.0001). CONCLUSION Due to the scarcity of pediatric NTCP data available, sensitivity analyses were performed using plausible ranges based on published adult data. In the clinical scenario where, if female pediatric patients were 20% more radiosensitive (lower TD50 value), they could be up to twice as likely to experience side-effects of brainstem necrosis and cochlea tinnitus compared to males, highlighting the need for considering the sex in NTCP models. Based on our sensitivity analyses, age and sex of a pediatric patient could significantly affect the resultant NTCP from cranial radiotherapy, especially at higher α/β values.
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Affiliation(s)
- Mikaela Dell'Oro
- Cancer Research Institute, University of South Australia, Adelaide, Australia.,Department of Radiation Oncology, Royal Adelaide Hospital, Adelaide, Australia
| | - Puthenparampil Wilson
- Department of Radiation Oncology, Royal Adelaide Hospital, Adelaide, Australia.,UniSA STEM, University of South Australia, Adelaide, Australia
| | - Michala Short
- Cancer Research Institute, University of South Australia, Adelaide, Australia
| | - Chia-Ho Hua
- Department of Radiation Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA
| | - Thomas E Merchant
- Department of Radiation Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA
| | - Eva Bezak
- Cancer Research Institute, University of South Australia, Adelaide, Australia.,Department of Physics, University of Adelaide, Adelaide, Australia
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Cardilin T, Almquist J, Jirstrand M, Zimmermann A, Lignet F, El Bawab S, Gabrielsson J. Exposure-response modeling improves selection of radiation and radiosensitizer combinations. J Pharmacokinet Pharmacodyn 2021; 49:167-178. [PMID: 34623558 PMCID: PMC8940791 DOI: 10.1007/s10928-021-09784-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2021] [Accepted: 09/19/2021] [Indexed: 10/28/2022]
Abstract
A central question in drug discovery is how to select drug candidates from a large number of available compounds. This analysis presents a model-based approach for comparing and ranking combinations of radiation and radiosensitizers. The approach is quantitative and based on the previously-derived Tumor Static Exposure (TSE) concept. Combinations of radiation and radiosensitizers are evaluated based on their ability to induce tumor regression relative to toxicity and other potential costs. The approach is presented in the form of a case study where the objective is to find the most promising candidate out of three radiosensitizing agents. Data from a xenograft study is described using a nonlinear mixed-effects modeling approach and a previously-published tumor model for radiation and radiosensitizing agents. First, the most promising candidate is chosen under the assumption that all compounds are equally toxic. The impact of toxicity in compound selection is then illustrated by assuming that one compound is more toxic than the others, leading to a different choice of candidate.
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Affiliation(s)
- Tim Cardilin
- Fraunhofer-Chalmers Centre, Chalmers Science Park, Gothenburg, Sweden. .,Department of Mathematical Sciences, Chalmers University of Technology and University of Gothenburg, Gothenburg, Sweden.
| | - Joachim Almquist
- Fraunhofer-Chalmers Centre, Chalmers Science Park, Gothenburg, Sweden.,Clinical Pharmacology and Quantitative Pharmacology, Clinical Pharmacology & Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden
| | - Mats Jirstrand
- Fraunhofer-Chalmers Centre, Chalmers Science Park, Gothenburg, Sweden
| | - Astrid Zimmermann
- Translation Innovation Platform Oncology, Merck KGaA, Darmstadt, Germany
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Kanehira T, van Kranen S, Jansen T, Hamming-Vrieze O, Al-Mamgani A, Sonke JJ. Comparisons of normal tissue complication probability models derived from planned and delivered dose for head and neck cancer patients. Radiother Oncol 2021; 164:209-215. [PMID: 34619234 DOI: 10.1016/j.radonc.2021.09.015] [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: 05/07/2021] [Revised: 08/24/2021] [Accepted: 09/18/2021] [Indexed: 11/15/2022]
Abstract
BACKGROUND AND PURPOSE Normal tissue complication probability (NTCP) models are typically derived from the planned dose distribution, which can deviate from the delivered dose due to anatomical day-to-day variations. The aim of this study was to compare NTCP models derived from the planned and the delivered dose for head and neck cancer (HNC) patients. MATERIAL AND METHOD 322 HNC patients who received radiotherapy with daily CBCT guidance were included in this retrospective study. The delivered dose was estimated by deformably accumulating dose from daily CBCT to planning anatomy. We used a Lyman-Kutcher-Burman NTCP model, to relate the equivalent uniform dose (EUD) of organs at risk (OAR) with oral mucositis, xerostomia and dysphagia respectively. We compared the model parameters and performances. RESULTS The median differences between planned and delivered EUD to the OARs were significantly larger for patients with toxicity than without for acute dysphagia (≥G2 and ≥G3) and late dysphagia (≥G3) (p < 0.05). Those differences resulted in small differences in steepness and agreement to the data between delivered- and planned-fitted NTCP curves, and the differences were not significant. The differences in AUC were less than 0.01. CONCLUSION Differences between delivered and planned dose did not lead to significant differences in NTCP curves. The additional clinical relevance of NTCP models using accumulated dose for oral mucositis, xerostomia and dysphagia in HNC radiotherapy is likely to be limited.
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Affiliation(s)
- Takahiro Kanehira
- Department of Radiation Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Simon van Kranen
- Department of Radiation Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Tomas Jansen
- Department of Radiation Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Olga Hamming-Vrieze
- Department of Radiation Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Abrahim Al-Mamgani
- Department of Radiation Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Jan-Jakob Sonke
- Department of Radiation Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
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Figlia V, Simonetto C, Eidemüller M, Naccarato S, Sicignano G, De Simone A, Ruggieri R, Mazzola R, Matuschek C, Bölke E, Pazos M, Niyazi M, Belka C, Alongi F, Corradini S. Mammary Chain Irradiation in Left-Sided Breast Cancer: Can We Reduce the Risk of Secondary Cancer and Ischaemic Heart Disease with Modern Intensity-Modulated Radiotherapy Techniques? Breast Care (Basel) 2021; 16:358-367. [PMID: 34602941 DOI: 10.1159/000509779] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2020] [Accepted: 06/29/2020] [Indexed: 11/19/2022] Open
Abstract
Introduction The aim of the present study was to estimate the impact of the addition of internal mammary chain (IMC) irradiation in node-positive left-sided breast cancer (BC) patients undergoing regional nodal irradiation (RNI) and comparatively evaluate excess relative and absolute risks of radiation-induced lung cancer/BC and ischaemic heart disease for intensity-modulated radiotherapy (IMRT) versus 3D conformal radiotherapy (3D-CRT). Methods Four treatment plans were created (3D-CRT and IMRT -/+ IMC) for each of the 10 evaluated patients, and estimates of excess relative risk (ERR) and 10-year excess absolute risk (EAR) were calculated for radiation-induced lung cancer/BC and coronary events using linear, linear-exponential and plateau models. Results The addition of IMC irradiation to RNI significantly increased the dose exposure of the heart, lung and contralateral breast using both techniques, increasing ERR for secondary lung cancer (58 vs. 44%, p = 0.002), contralateral BC (49 vs. 31%, p = 0.002) and ischaemic heart disease (41 vs. 27%, p = 0.002, IMRT plans). IMRT significantly reduced the mean cardiac dose and mean lung dose as compared to 3D-CRT, decreasing ERR for major coronary events (64% 3D-CRT vs. 41% IMRT, p = 0.002) and ERR for secondary lung cancer (75 vs. 58%, p = 0.004) in IMC irradiation, without a significant impact on secondary contralateral BC risks. Conclusion Although IMC irradiation has been shown to increase survival rates in node-positive BC patients, it increased dose exposure of organs at risk in left-sided BC, resulting in significantly increased risks for secondary lung cancer/contralateral BC and ischaemic heart disease. In this setting, the adoption of IMRT seems advantageous when compared to 3D-CRT.
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Affiliation(s)
- Vanessa Figlia
- Advanced Radiation Oncology Department, IRCCS Sacro Cuore Don Calabria Hospital, Negrar, Italy
| | | | - Markus Eidemüller
- Institute of Radiation Medicine, Helmholtz Center Munich, Munich, Germany
| | - Stefania Naccarato
- Advanced Radiation Oncology Department, IRCCS Sacro Cuore Don Calabria Hospital, Negrar, Italy
| | - Gianluisa Sicignano
- Advanced Radiation Oncology Department, IRCCS Sacro Cuore Don Calabria Hospital, Negrar, Italy
| | - Antonio De Simone
- Advanced Radiation Oncology Department, IRCCS Sacro Cuore Don Calabria Hospital, Negrar, Italy
| | - Ruggero Ruggieri
- Advanced Radiation Oncology Department, IRCCS Sacro Cuore Don Calabria Hospital, Negrar, Italy
| | - Rosario Mazzola
- Advanced Radiation Oncology Department, IRCCS Sacro Cuore Don Calabria Hospital, Negrar, Italy
| | - Christiane Matuschek
- Department of Radiation Oncology, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany
| | - Edwin Bölke
- Department of Radiation Oncology, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany
| | - Montserrat Pazos
- Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany
| | - Maximilian Niyazi
- Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany
| | - Claus Belka
- Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany
| | - Filippo Alongi
- Advanced Radiation Oncology Department, IRCCS Sacro Cuore Don Calabria Hospital, Negrar, Italy.,University of Brescia, Brescia, Italy
| | - Stefanie Corradini
- Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany
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Pramanik S, Bera S, Roy S, Ray A, Sarkar S, Majumder D. Dosimetric validation of two different radiobiological models for parotid gland functionality of tongue cancer. PRECISION RADIATION ONCOLOGY 2021. [DOI: 10.1002/pro6.1130] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Affiliation(s)
- Srimanta Pramanik
- Department of Radiation Oncology Ruby General Hospital E.M. Bypass, Kasba, Golpark Kolkata West Bengal India
| | - Soumen Bera
- Department of Radiation Oncology Ruby General Hospital E.M. Bypass, Kasba, Golpark Kolkata West Bengal India
| | - Sanjoy Roy
- Department of Radiation Oncology Ruby General Hospital E.M. Bypass, Kasba, Golpark Kolkata West Bengal India
| | - Amitabh Ray
- Department of Radiation Oncology Ruby General Hospital E.M. Bypass, Kasba, Golpark Kolkata West Bengal India
| | - Sandip Sarkar
- Department of Radiation Oncology Ruby General Hospital E.M. Bypass, Kasba, Golpark Kolkata West Bengal India
| | - Dipanjan Majumder
- Department of Radiation Oncology Ruby General Hospital E.M. Bypass, Kasba, Golpark Kolkata West Bengal India
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Rezaeijo SM, Hashemi B, Mofid B, Bakhshandeh M, Mahdavi A, Hashemi MS. The feasibility of a dose painting procedure to treat prostate cancer based on mpMR images and hierarchical clustering. Radiat Oncol 2021; 16:182. [PMID: 34544468 PMCID: PMC8454023 DOI: 10.1186/s13014-021-01906-2] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2021] [Accepted: 09/06/2021] [Indexed: 11/30/2022] Open
Abstract
BACKGROUND We aimed to assess the feasibility of a dose painting (DP) procedure, known as simultaneous integrated boost intensity modulated radiation Therapy (SIB-IMRT), for treating prostate cancer with dominant intraprostatic lesions (DILs) based on multi-parametric magnetic resonance (mpMR) images and hierarchical clustering with a machine learning technique. METHODS The mpMR images of 120 patients were used to create hierarchical clustering and draw a dendrogram. Three clusters were selected for performing agglomerative clustering. Then, the DIL acquired from the mpMR images of 20 patients were categorized into three groups to have them treated with a DP procedure being composed of three planning target volumes (PTVs) determined as PTV1, PTV2, and PTV3 in treatment plans. The DP procedure was carried out on the patients wherein a total dose of 80, 85 and 91 Gy were delivered to the PTV1, PTV2, and PTV3, respectively. Dosimetric and radiobiologic parameters [Tumor Control Probability (TCP) and Normal Tissue Complication Probability (NTCP)] of the DP procedure were compared with those of the conventional IMRT and Three-Dimensional Conformal Radiation Therapy (3DCRT) procedures carried out on another group of 20 patients. A post-treatment follow-up was also made four months after the radiotherapy procedures. RESULTS All the dosimetric variables and the NTCPs of the organs at risks (OARs) revealed no significant difference between the DP and IMRT procedures. Regarding the TCP of three investigated PTVs, significant differences were observed between the DP versus IMRT and also DP versus 3DCRT procedures. At post-treatment follow-up, the DIL volumes and apparent diffusion coefficient (ADC) values in the DP group differed significantly (p-value < 0.001) from those of the IMRT. However, the whole prostate ADC and prostate-specific antigen (PSA) indicated no significant difference (p-value > 0.05) between the DP versus IMRT. CONCLUSIONS The results of this comprehensive clinical trial illustrated the feasibility of our DP procedure for treating prostate cancer based on mpMR images validated with acquired patients' dosimetric and radiobiologic assessment and their follow-ups. This study confirms significant potential of the proposed DP procedure as a promising treatment planning to achieve effective dose escalation and treatment for prostate cancer. TRIAL REGISTRATION IRCT20181006041257N1; Iranian Registry of Clinical Trials, Registered: 23 October 2019, https://en.irct.ir/trial/34305 .
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Affiliation(s)
- Seyed Masoud Rezaeijo
- Department of Medical Physics, Faculty of Medical Sciences, Tarbiat Modares University, Al-Ahmad and Chamran Cross, 1411713116 Tehran, Iran
| | - Bijan Hashemi
- Department of Medical Physics, Faculty of Medical Sciences, Tarbiat Modares University, Al-Ahmad and Chamran Cross, 1411713116 Tehran, Iran
| | - Bahram Mofid
- Department of Radiation Oncology, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohsen Bakhshandeh
- Department of Radiology Technology, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Arash Mahdavi
- Department of Radiology, Modares Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Modeling of Tumor Control Probability in Stereotactic Body Radiation Therapy for Adrenal Tumors. Int J Radiat Oncol Biol Phys 2021; 110:217-226. [PMID: 33864824 DOI: 10.1016/j.ijrobp.2020.05.062] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2020] [Accepted: 05/30/2020] [Indexed: 02/08/2023]
Abstract
PURPOSE Stereotactic body radiation therapy (SBRT) in the management of adrenal metastases is emerging as a well-tolerated, effective method of treatment for patients with limited metastatic disease. SBRT planning and treatment utilization are widely variable, and publications report heterogeneous radiation dose fractionation schemes and treatment outcomes. The objective of this analysis was to review the current literature on SBRT for adrenal metastases and to develop treatment guidelines and a model for tumor control probability of SBRT for adrenal metastases based on these publications. METHODS AND MATERIALS A literature search of all studies on SBRT for adrenal metastases published from 2008 to 2017 was performed, and outcomes in these studies were reviewed. Local control (LC) rates were fit to a statistically significant Poisson model using maximum likelihood estimation techniques. RESULTS One-year LC greater than 95% was achieved at an approximated biological equivalent dose with α/β = 10 Gy of 116.4 Gy. CONCLUSIONS While respecting normal tissue tolerances, tumor doses greater than or equal to a biological equivalent dose with α/β = 10 Gy of 116.4 Gy are recommended to achieve high LC. Further studies following unified reporting standards are needed for more robust prediction.
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Radiobiological assessment of nasopharyngeal cancer IMRT using various collimator angles and non-coplanar fields. JOURNAL OF RADIOTHERAPY IN PRACTICE 2021. [DOI: 10.1017/s1460396919000943] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
AbstractAim:The aim of this study was to evaluate clinical efficacy and radiobiological outcome of intensity-modulated radiation therapy (IMRT) modalities using various collimator angles and non-coplanar fields for nasopharyngeal cancer (NPC).Materials and methods:A 70-Gy planning target volume dose was administered for 30 NPC patients referred for IMRT. Standard IMRT plans were constructed based on the target and organs at risk (OARs) volume; and dose constraints recommended by Radiation Therapy Oncology Group (RTOG). Using various collimator angles and non-coplanar fields, 11 different additional IMRT protocols were investigated. Homogeneity indexes (HIs) and conformation numbers (CNs) were calculated. Poisson and relative seriality models were utilised for estimating tumour control probability (TCP) and normal tissue complication probabilities (NTCPs), respectively.Results:Various collimator angles and non-coplanar fields had no significant effect on HI, CN and TCP, while significant effects were noted for some OARs, with a maximum mean dose (Dmax). No significant differences were observed among the calculated NTCPs of all the IMRT protocols. However, the protocol with 10° collimator angle (for five fields out of seven) and 8° couch angle had the lowest NTCP. Furthermore, the standard and some of non-coplanar IMRT protocols led to the reduction in OARs Dmax.Conclusions:Using appropriate standard/non-coplanar IMRT protocols for NPC treatment could potentially reduce the dose to the OARs and the probability of inducing secondary cancer in patients.
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Alevronta E, Skokic V, Dunberger G, Bull C, Bergmark K, Jörnsten R, Steineck G. Dose-response relationships of intestinal organs and excessive mucus discharge after gynaecological radiotherapy. PLoS One 2021; 16:e0250004. [PMID: 33861779 PMCID: PMC8051803 DOI: 10.1371/journal.pone.0250004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2020] [Accepted: 03/29/2021] [Indexed: 12/03/2022] Open
Abstract
BACKGROUND The study aims to determine possible dose-volume response relationships between the rectum, sigmoid colon and small intestine and the 'excessive mucus discharge' syndrome after pelvic radiotherapy for gynaecological cancer. METHODS AND MATERIALS From a larger cohort, 98 gynaecological cancer survivors were included in this study. These survivors, who were followed for 2 to 14 years, received external beam radiation therapy but not brachytherapy and not did not have stoma. Thirteen of the 98 developed excessive mucus discharge syndrome. Three self-assessed symptoms were weighted together to produce a score interpreted as 'excessive mucus discharge' syndrome based on the factor loadings from factor analysis. The dose-volume histograms (DVHs) for rectum, sigmoid colon, small intestine for each survivor were exported from the treatment planning systems. The dose-volume response relationships for excessive mucus discharge and each organ at risk were estimated by fitting the data to the Probit, RS, LKB and gEUD models. RESULTS The small intestine was found to have steep dose-response curves, having estimated dose-response parameters: γ50: 1.28, 1.23, 1.32, D50: 61.6, 63.1, 60.2 for Probit, RS and LKB respectively. The sigmoid colon (AUC: 0.68) and the small intestine (AUC: 0.65) had the highest AUC values. For the small intestine, the DVHs for survivors with and without excessive mucus discharge were well separated for low to intermediate doses; this was not true for the sigmoid colon. Based on all results, we interpret the results for the small intestine to reflect a relevant link. CONCLUSION An association was found between the mean dose to the small intestine and the occurrence of 'excessive mucus discharge'. When trying to reduce and even eliminate the incidence of 'excessive mucus discharge', it would be useful and important to separately delineate the small intestine and implement the dose-response estimations reported in the study.
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Affiliation(s)
- Eleftheria Alevronta
- Division of Clinical Cancer Epidemiology, Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
| | - Viktor Skokic
- Division of Clinical Cancer Epidemiology, Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
| | - Gail Dunberger
- Department of Health Care Sciences, Ersta Sköndal Bräcke University College, Stockholm, Sweden
| | - Cecilia Bull
- Division of Clinical Cancer Epidemiology, Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
| | - Karin Bergmark
- Division of Clinical Cancer Epidemiology, Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
| | | | - Gunnar Steineck
- Division of Clinical Cancer Epidemiology, Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
- Division of Clinical Cancer Epidemiology, Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden
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Hrycushko B, Medin PM. Effects From Nonuniform Dose Distribution in the Spinal Nerves of Pigs: Analysis of Normal Tissue Complication Probability Models. Int J Radiat Oncol Biol Phys 2021; 109:1570-1579. [PMID: 33171201 DOI: 10.1016/j.ijrobp.2020.11.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2020] [Revised: 10/15/2020] [Accepted: 11/02/2020] [Indexed: 10/23/2022]
Abstract
PURPOSE Our purpose was to evaluate normal tissue complication probability (NTCP) models for their ability to describe the increase in tolerance as the length of irradiated spinal nerve is reduced in a pig. METHODS AND MATERIALS Common phenomenological and semimechanistic NTCP models were fit using the maximum likelihood estimate method to dose-response data from spinal nerve irradiation studies in pigs. Statistical analysis was used to compare how well each model fit the data. Model parameters were then applied to a previously published dose distribution used for spinal cord irradiation in rats under the assumption of a similar dose-response. RESULTS The Lyman-Kutcher-Burman model, relative seriality, and critical volume model fit the spinal nerve data equally well, but the mean dose logistic and relative seriality models gave the best fit after penalizing for the number of model parameters. The minimum dose logistic regression model was the only model showing a lack of fit. When extrapolated to a 0.5-cm simulated square-wave-like dose distribution, the serial behaving models showed negligible increase in dose-response curve. The Lyman-Kutcher-Burman model and relative seriality models showed significant shifting of NTCP curves due to parallel behaving parameters. The critical volume model gave the closest match to the rat data. CONCLUSIONS Several phenomenological and semimechanistic models were observed to adequately describe the increase in the radiation tolerance of the spinal nerves when changing the irradiated length from 1.5 to 0.5 cm. Contrary to common perception, model parameters suggest parallel behaving tissue architecture. Under the assumption that the spinal nerve response to radiation is similar to that of the spinal cord, only the critical volume model was robust when extrapolating to outcome data from a 0.5-cm square-wave-like dose distribution, as was delivered in rodent spinal cord irradiation research.
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Affiliation(s)
- Brian Hrycushko
- Department of Radiation Oncology, UT Southwestern Medical Center, Dallas, Texas.
| | - Paul M Medin
- Department of Radiation Oncology, UT Southwestern Medical Center, Dallas, Texas
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Mavroidis P, Pearlstein KA, Moon DH, Xu V, Royce TJ, Weiner AA, Shen CJ, Marks LB, Chera BS, Das SK, Wang K. NTCP modeling and dose-volume correlations for acute xerostomia and dry eye after whole brain radiation. Radiat Oncol 2021; 16:56. [PMID: 33743773 PMCID: PMC7981795 DOI: 10.1186/s13014-021-01786-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2021] [Accepted: 03/12/2021] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Whole brain radiation (WBRT) may lead to acute xerostomia and dry eye from incidental parotid and lacrimal exposure, respectively. We performed a prospective observational study to assess the incidence/severity of this toxicity. We herein perform a secondary analysis relating parotid and lacrimal dosimetric parameters to normal tissue complication probability (NTCP) rates and associated models. METHODS Patients received WBRT to 25-40 Gy in 10-20 fractions using 3D-conformal radiation therapy without prospective delineation of the parotids or lacrimals. Patients completed questionnaires at baseline and 1 month post-WBRT. Xerostomia was assessed using the University of Michigan xerostomia score (scored 0-100, toxicity defined as ≥ 20 pt increase) and xerostomia bother score (scored from 0 to 3, toxicity defined as ≥ 2 pt increase). Dry eye was assessed using the Subjective Evaluation of Symptom of Dryness (SESoD, scored from 0 to 4, toxicity defined as ≥ 2 pt increase). The clinical data were fitted by the Lyman-Kutcher-Burman (LKB) and Relative Seriality (RS) NTCP models. RESULTS Of 55 evaluable patients, 19 (35%) had ≥ 20 point increase in xerostomia score, 11 (20%) had ≥ 2 point increase in xerostomia bother score, and 13 (24%) had ≥ 2 point increase in SESoD score. For xerostomia, parotid V10Gy-V20Gy correlated best with toxicity, with AUC 0.68 for xerostomia score and 0.69-0.71 for bother score. The values for the D50, m and n parameters of the LKB model were 22.3 Gy, 0.84 and 1.0 for xerostomia score and 28.4 Gy, 0.55 and 1.0 for bother score, respectively. The corresponding values for the D50, γ and s parameters of the RS model were 23.5 Gy, 0.28 and 0.0001 for xerostomia score and 32.0 Gy, 0.45 and 0.0001 for bother score, respectively. For dry eye, lacrimal V10Gy-V15Gy were found to correlate best with toxicity, with AUC values from 0.67 to 0.68. The parameter values of the LKB model were 53.5 Gy, 0.74 and 1.0, whereas of the RS model were 54.0 Gy, 0.37 and 0.0001, respectively. CONCLUSIONS Xerostomia was most associated with parotid V10Gy-V20Gy, and dry eye with lacrimal V10Gy-V15Gy. NTCP models were successfully created for both toxicities and may help clinicians refine dosimetric goals and assess levels of risk in patients receiving palliative WBRT.
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Affiliation(s)
- Panayiotis Mavroidis
- Department of Radiation Oncology, University of North Carolina, 101 Manning Dr., Chapel Hill, NC, 27599-7512, USA.
| | - Kevin A Pearlstein
- Department of Radiation Oncology, University of North Carolina, 101 Manning Dr., Chapel Hill, NC, 27599-7512, USA
| | - Dominic H Moon
- Department of Radiation Oncology, University of North Carolina, 101 Manning Dr., Chapel Hill, NC, 27599-7512, USA
| | - Victoria Xu
- Department of Radiation Oncology, University of North Carolina, 101 Manning Dr., Chapel Hill, NC, 27599-7512, USA
| | - Trevor J Royce
- Department of Radiation Oncology, University of North Carolina, 101 Manning Dr., Chapel Hill, NC, 27599-7512, USA
| | - Ashley A Weiner
- Department of Radiation Oncology, University of North Carolina, 101 Manning Dr., Chapel Hill, NC, 27599-7512, USA
| | - Colette J Shen
- Department of Radiation Oncology, University of North Carolina, 101 Manning Dr., Chapel Hill, NC, 27599-7512, USA
| | - Lawrence B Marks
- Department of Radiation Oncology, University of North Carolina, 101 Manning Dr., Chapel Hill, NC, 27599-7512, USA
| | - Bhishamjit S Chera
- Department of Radiation Oncology, University of North Carolina, 101 Manning Dr., Chapel Hill, NC, 27599-7512, USA
| | - Shiva K Das
- Department of Radiation Oncology, University of North Carolina, 101 Manning Dr., Chapel Hill, NC, 27599-7512, USA
| | - Kyle Wang
- Department of Radiation Oncology, University of North Carolina, 101 Manning Dr., Chapel Hill, NC, 27599-7512, USA
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Varnava M, Sumida I, Oda M, Kurosu K, Isohashi F, Seo Y, Otani K, Ogawa K. Dosimetric comparison between volumetric modulated arc therapy planning techniques for prostate cancer in the presence of intrafractional organ deformation. JOURNAL OF RADIATION RESEARCH 2021; 62:309-318. [PMID: 33341880 PMCID: PMC7948894 DOI: 10.1093/jrr/rraa123] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/14/2020] [Revised: 09/24/2020] [Accepted: 09/30/2020] [Indexed: 06/12/2023]
Abstract
The purpose of this study was to compare single-arc (SA) and double-arc (DA) treatment plans, which are planning techniques often used in prostate cancer volumetric modulated arc therapy (VMAT), in the presence of intrafractional deformation (ID) to determine which technique is superior in terms of target dose coverage and sparing of the organs at risk (OARs). SA and DA plans were created for 27 patients with localized prostate cancer. ID was introduced to the clinical target volume (CTV), rectum and bladder to obtain blurred dose distributions using an in-house software. ID was based on the motion probability function of each structure voxel and the intrafractional motion of the respective organs. From the resultant blurred dose distributions of SA and DA plans, various parameters, including the tumor control probability, normal tissue complication probability, homogeneity index, conformity index, modulation complexity score for VMAT, dose-volume indices and monitor units (MUs), were evaluated to compare the two techniques. Statistical analysis showed that most CTV and rectum parameters were significantly larger for SA plans than for DA plans (P < 0.05). Furthermore, SA plans had fewer MUs and were less complex (P < 0.05). The significant differences observed had no clinical significance, indicating that both plans are comparable in terms of target and OAR dosimetry when ID is considered. The use of SA plans is recommended for prostate cancer VMAT because they can be delivered in shorter treatment times than DA plans, and therefore benefit the patients.
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Affiliation(s)
- Maria Varnava
- Corresponding author. Department of Radiation Oncology, Osaka University Graduate School of Medicine, 2-2 (D10) Yamadaoka, Suita, Osaka, 565-0871, Japan. Tel: +81-6-6879-3482; Fax: +81-6-6879-3489;
| | - Iori Sumida
- Department of Radiation Oncology, Osaka University Graduate School of Medicine, 2-2 (D10) Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Michio Oda
- Department of Medical Technology, Osaka University Hospital, 2-15 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Keita Kurosu
- Department of Medical Technology, Osaka University Hospital, 2-15 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Fumiaki Isohashi
- Department of Radiation Oncology, Osaka University Graduate School of Medicine, 2-2 (D10) Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Yuji Seo
- Department of Radiation Oncology, Osaka University Graduate School of Medicine, 2-2 (D10) Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Keisuke Otani
- Department of Radiation Oncology, Osaka University Graduate School of Medicine, 2-2 (D10) Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Kazuhiko Ogawa
- Department of Radiation Oncology, Osaka University Graduate School of Medicine, 2-2 (D10) Yamadaoka, Suita, Osaka, 565-0871, Japan
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Sammer M, Girst S, Dollinger G. Optimizing proton minibeam radiotherapy by interlacing and heterogeneous tumor dose on the basis of calculated clonogenic cell survival. Sci Rep 2021; 11:3533. [PMID: 33574390 PMCID: PMC7878903 DOI: 10.1038/s41598-021-81708-4] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2020] [Accepted: 12/23/2020] [Indexed: 01/30/2023] Open
Abstract
Proton minibeam radiotherapy (pMBRT) is a spatial fractionation method using sub-millimeter beams at center-to-center (ctc) distances of a few millimeters to widen the therapeutic index by reduction of side effects in normal tissues. Interlaced minibeams from two opposing or four orthogonal directions are calculated to minimize side effects. In particular, heterogeneous dose distributions applied to the tumor are investigated to evaluate optimized sparing capabilities of normal tissues at the close tumor surrounding. A 5 cm thick tumor is considered at 10 cm depth within a 25 cm thick water phantom. Pencil and planar minibeams are interlaced from two (opposing) directions as well as planar beams from four directions. An initial beam size of σ0 = 0.2 mm (standard deviation) is assumed in all cases. Tissue sparing potential is evaluated by calculating mean clonogenic cell survival using a linear-quadratic model on the calculated dose distributions. Interlacing proton minibeams for homogeneous irradiation of the tumor has only minor benefits for the mean clonogenic cell survival compared to unidirectional minibeam irradiation modes. Enhanced mean cell survival, however, is obtained when a heterogeneous dose distribution within the tumor is permitted. The benefits hold true even for an elevated mean tumor dose, which is necessary to avoid cold spots within the tumor in concerns of a prescribed dose. The heterogeneous irradiation of the tumor allows for larger ctc distances. Thus, a high mean cell survival of up to 47% is maintained even close to the tumor edges for single fraction doses in the tumor of at least 10 Gy. Similar benefits would result for heavy ion minibeams with the advantage of smaller minibeams in deep tissue potentially offering even increased tissue sparing. The enhanced mean clonogenic cell survival through large ctc distances for interlaced pMBRT with heterogeneous tumor dose distribution results in optimum tissue sparing potential. The calculations show the largest enhancement of the mean cell survival in normal tissue for high-dose fractions. Thus, hypo-fractionation or even single dose fractions become possible for tumor irradiation. A widened therapeutic index at big cost reductions is offered by interlaced proton or heavy ion minibeam therapy.
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Affiliation(s)
- Matthias Sammer
- Institut für Angewandte Physik und Messtechnik (LRT2), Universität der Bundeswehr München, 85579, Neubiberg, Germany.
| | - Stefanie Girst
- Institut für Angewandte Physik und Messtechnik (LRT2), Universität der Bundeswehr München, 85579, Neubiberg, Germany
| | - Günther Dollinger
- Institut für Angewandte Physik und Messtechnik (LRT2), Universität der Bundeswehr München, 85579, Neubiberg, Germany
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Marteinsdottir M, Wang CC, McNamara A, Depauw N, Shin J, Paganetti H. The impact of variable relative biological effectiveness in proton therapy for left-sided breast cancer when estimating normal tissue complications in the heart and lung. Phys Med Biol 2021; 66:035023. [PMID: 33522498 DOI: 10.1088/1361-6560/abd230] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
The aim of this study was to evaluate the clinical impact of relative biological effectiveness (RBE) variations in proton beam scanning treatment (PBS) for left-sided breast cancer versus the assumption of a fixed RBE of 1.1, particularly in the context of comparisons with photon-based three-dimensional conformal radiotherapy (3DCRT) and volumetric modulated arc therapy (VMAT). Ten patients receiving radiation treatment to the whole breast/chest wall and regional lymph nodes were selected for each modality. For PBS, the dose distributions were re-calculated with both a fixed RBE and a variable RBE using an empirical RBE model. Dosimetric indices based on dose-volume histogram analysis were calculated for the entire heart wall, left anterior descending artery (LAD) and left lung. Furthermore, normal tissue toxicity probabilities for different endpoints were evaluated. The results show that applying a variable RBE significantly increases the RBE-weighted dose and consequently the calculated dosimetric indices increases for all organs compared to a fixed RBE. The mean dose to the heart and the maximum dose to the LAD and the left lung are significantly lower for PBS assuming a fixed RBE compared to 3DCRT. However, no statistically significant difference is seen when a variable RBE is applied. For a fixed RBE, lung toxicities are significantly lower compared to 3DCRT but when applying a variable RBE, no statistically significant differences are noted. A disadvantage is seen for VMAT over both PBS and 3DCRT. One-to-one plan comparison on 8 patients between PBS and 3DCRT shows similar results. We conclude that dosimetric analysis for all organs and toxicity estimation for the left lung might be underestimated when applying a fixed RBE for protons. Potential RBE variations should therefore be considered as uncertainty bands in outcome analysis.
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Affiliation(s)
- Maria Marteinsdottir
- Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA 02114, United States of America. Faculty of Physical Sciences, University of Iceland, Dunhaga 5, IS-107 Reykjavik, Iceland
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Shirvani SM, Huntzinger CJ, Melcher T, Olcott PD, Voronenko Y, Bartlett-Roberto J, Mazin S. Biology-guided radiotherapy: redefining the role of radiotherapy in metastatic cancer. Br J Radiol 2021; 94:20200873. [PMID: 33112685 PMCID: PMC7774706 DOI: 10.1259/bjr.20200873] [Citation(s) in RCA: 43] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2020] [Revised: 09/30/2020] [Accepted: 10/05/2020] [Indexed: 12/14/2022] Open
Abstract
The emerging biological understanding of metastatic cancer and proof-of-concept clinical trials suggest that debulking all gross disease holds great promise for improving patient outcomes. However, ablation of multiple targets with conventional external beam radiotherapy systems is burdensome, which limits investigation and utilization of complete metastatic ablation in the majority of patients with advanced disease. To overcome this logistical hurdle, technical innovation is necessary. Biology-guided radiotherapy (BgRT) is a new external beam radiotherapy delivery modality combining positron emission tomography-computed tomography (PET-CT) with a 6 MV linear accelerator. The key innovation is continuous response of the linear accelerator to outgoing tumor PET emissions with beamlets of radiotherapy at subsecond latency. This allows the deposited dose to track tumors in real time. Multiple new hardware and algorithmic advances further facilitate this low-latency feedback process. By transforming tumors into their own fiducials after intravenous injection of a radiotracer, BgRT has the potential to enable complete metastatic ablation in a manner efficient for a single patient and scalable to entire populations with metastatic disease. Future trends may further enhance the utility of BgRT in the clinic as this technology dovetails with other innovations in radiotherapy, including novel dose painting and fractionation schemes, radiomics, and new radiotracers.
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Moiseenko V, Marks LB, Grimm J, Jackson A, Milano MT, Hattangadi-Gluth JA, Huynh-Le MP, Pettersson N, Yorke E, El Naqa I. A Primer on Dose-Response Data Modeling in Radiation Therapy. Int J Radiat Oncol Biol Phys 2020; 110:11-20. [PMID: 33358230 DOI: 10.1016/j.ijrobp.2020.11.020] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2020] [Revised: 11/05/2020] [Accepted: 11/05/2020] [Indexed: 12/11/2022]
Abstract
An overview of common approaches used to assess a dose response for radiation therapy-associated endpoints is presented, using lung toxicity data sets analyzed as a part of the High Dose per Fraction, Hypofractionated Treatment Effects in the Clinic effort as an example. Each component presented (eg, data-driven analysis, dose-response analysis, and calculating uncertainties on model prediction) is addressed using established approaches. Specifically, the maximum likelihood method was used to calculate best parameter values of the commonly used logistic model, the profile-likelihood to calculate confidence intervals on model parameters, and the likelihood ratio to determine whether the observed data fit is statistically significant. The bootstrap method was used to calculate confidence intervals for model predictions. Correlated behavior of model parameters and implication for interpreting dose response are discussed.
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Affiliation(s)
- Vitali Moiseenko
- Department of Radiation Medicine and Applied Sciences, University of California, San Diego, La Jolla, California.
| | - Lawrence B Marks
- Department of Radiation Oncology and the Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| | - Jimm Grimm
- Department of Radiation Oncology, Geisinger Health System, Danville, Pennsylvania
| | - Andrew Jackson
- Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Michael T Milano
- Department of Radiation Oncology, University of Rochester, Rochester, New York
| | - Jona A Hattangadi-Gluth
- Department of Radiation Medicine and Applied Sciences, University of California, San Diego, La Jolla, California
| | - Minh-Phuong Huynh-Le
- Department of Radiation Medicine and Applied Sciences, University of California, San Diego, La Jolla, California
| | - Niclas Pettersson
- Department of Radiation Physics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Medical Physics and Biomedical Engineering, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Ellen Yorke
- Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Issam El Naqa
- Department of Machine Learning, Moffitt Cancer Center, Tampa, Florida
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