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Naoum GE, Dobinda K, Yalamanchili A, Ho A, Yadav P, Nesbit E, Donnelly E, Kocherginsky M, Strauss J. Protons Versus Photons Postmastectomy Radiation Therapy Effects on Breast Reconstruction Outcomes and Dosimetry Analysis. Int J Radiat Oncol Biol Phys 2025; 122:249-266. [PMID: 39947259 DOI: 10.1016/j.ijrobp.2025.01.034] [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: 11/13/2024] [Revised: 01/22/2025] [Accepted: 01/31/2025] [Indexed: 05/19/2025]
Abstract
PURPOSE To compare the impact of proton versus photon postmastectomy radiation therapy (PMRT) on implant-related complications. METHODS AND MATERIALS The records of patients with breast cancer treated with mastectomy and expander and/or implant reconstruction followed by PMRT at our institution between 2011 and 2022 were reviewed. Patients were divided into 2 groups by treatment modality: proton and photon groups. All identified patients in the proton group were treated using conventional fractionation, and radiobiological effectiveness (RBE) was scaled to 1.1. Recorded complications included infection/skin necrosis requiring operative debridement, capsular contracture necessitating capsulotomy, absolute reconstruction failure implying complete loss of reconstruction, and overall reconstruction failure defined as multiple revisions leading to replacement of the implant or salvage autologous reconstruction. Subgroup analysis for patients in the proton group explored the correlation between dosimetric parameters and complications. Logistic regression and Cox proportional hazards regression models were used. RESULTS A total of 203 patients with an overall median follow-up of 4.7 years were identified. Among those 203 patients, 50 patients (25%) received proton PMRT, while 153 patients (75%) received photon PMRT. The complication rates for proton versus photon therapies were infection/necrosis (20% vs 13%; OR, 1.6; P = .2), capsular contracture (30% vs 10%; OR, 3.9; P < .001), absolute reconstruction failure (16% vs 12%; OR, 1.4; P = .4), and overall reconstruction failure (56% vs 36%; OR, 2.2; P = .01). Sensitivity analyses and time-to-event models yielded similar results. The median (Dmean) for clinical target volume, implant, and skin was 50.6, 50.8, and 6.7 Gy (RBE), respectively. The median hot spot (D1cc) for clinical target volume, implant, and skin was 52.8, 52.7, and 49.8 Gy (RBE), respectively. None of these parameters were significantly correlated with complications. The 5-year local failure cumulative incidence was 0% versus 4% (P = .13) for proton and photon cohorts, respectively. CONCLUSIONS Proton PMRT was associated with higher rates of implant capsular contracture and reconstruction failures than photon PMRT with comparable local control. No dosimetric parameter correlated with reconstruction complications.
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Affiliation(s)
- George E Naoum
- Department of Radiation Oncology, Northwestern University, Northwestern Memorial Hospital, Chicago, Illinois.
| | - Katrina Dobinda
- Biostatistics Center, Northwestern University, Northwestern Memorial Hospital, Chicago, Illinois
| | - Amulya Yalamanchili
- Department of Radiation Oncology, Northwestern University, Northwestern Memorial Hospital, Chicago, Illinois
| | - Alexander Ho
- Department of Radiation Oncology, Northwestern University, Northwestern Memorial Hospital, Chicago, Illinois
| | - Poonam Yadav
- Department of Radiation Oncology, Northwestern University, Northwestern Memorial Hospital, Chicago, Illinois
| | - Eric Nesbit
- Department of Radiation Oncology, Northwestern University, Northwestern Memorial Hospital, Chicago, Illinois
| | - Eric Donnelly
- Department of Radiation Oncology, Northwestern University, Northwestern Memorial Hospital, Chicago, Illinois
| | - Masha Kocherginsky
- Biostatistics Center, Northwestern University, Northwestern Memorial Hospital, Chicago, Illinois
| | - Jonathan Strauss
- Department of Radiation Oncology, Northwestern University, Northwestern Memorial Hospital, Chicago, Illinois
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Li C, Dai H, Guo X, Zhou L, Jiang M. Comprehensive review of non-invasive-treatment-related cardiovascular toxicity in breast cancer. iScience 2025; 28:111759. [PMID: 40207253 PMCID: PMC11980005 DOI: 10.1016/j.isci.2025.111759] [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] [Indexed: 04/11/2025] Open
Abstract
Cardiovascular toxicity is a significant side effect of breast cancer treatment and has emerged as a leading cause of non-tumor-related deaths among breast cancer survivors, emphasizing the critical need for effective monitoring and management of these complications. As breast cancer remains the most prevalent cancer among women, advancements in survival rates have been achieved through treatments such as chemotherapy, targeted therapy, endocrine therapy, immunotherapy, and radiotherapy. This review provides a comprehensive understanding of the cardiovascular toxicity mechanisms associated with both established and emerging breast cancer therapies, identifies potential therapeutic targets and monitoring strategies, and highlights key deficiencies and challenges in the field. By offering insights into the early detection, prevention, and management of cardiovascular complications, this review aims to guide future research directions and clinical practices, ultimately improving outcomes for breast cancer patients.
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Affiliation(s)
- Cenyu Li
- Division of Cardiology, State Key Laboratory of Systems Medicine for Cancer, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai 200127, China
- Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Huijuan Dai
- Department of Breast Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
| | - Xinning Guo
- Division of Cardiology, State Key Laboratory of Systems Medicine for Cancer, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai 200127, China
| | - Liheng Zhou
- Department of Breast Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
| | - Meng Jiang
- Division of Cardiology, State Key Laboratory of Systems Medicine for Cancer, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai 200127, China
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Naoum GE, Ababneh HS, Niemierko A, Salama L, Ioannidou M, Smith BL, Colwell A, Taghian AG. Impact of Prepectoral Implant Placement and Radiation Modalities (Protons/Photons/Dosimetry) in Mastectomy Patients Undergoing Immediate Single Stage Direct-to-Implant Breast Reconstruction. Int J Radiat Oncol Biol Phys 2025; 121:1156-1167. [PMID: 39617361 DOI: 10.1016/j.ijrobp.2024.11.079] [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: 01/30/2024] [Revised: 10/26/2024] [Accepted: 11/07/2024] [Indexed: 01/24/2025]
Abstract
PURPOSE For patients with breast cancer receiving mastectomy with direct-to-implant (DTI) immediate breast reconstruction, placing the implant in the prepectoral or subpectoral plane remains debatable, especially in settings of postmastectomy radiation therapy (PMRT). METHODS AND MATERIALS We reviewed 3039 patients who underwent mastectomy and reconstruction at our institution between 2005 and 2020. Patients receiving DTI with and without PMRT were included. PMRT was delivered either with a photon (3-dimensional-conformal or volumetric arc therapy) or proton therapy, mainly with pencil-beam-scanning. All patients received conventional fractionation (50-50.4 Gy in 25-28 fractions). Primary endpoints were reconstruction complications defined as infection/necrosis requiring debridement; capsular contracture requiring capsulotomy; absolute reconstruction failure entailing permanent removal of the implant without replacement (ie, no salvage reconstruction); and overall reconstruction failure (removal of the implant for any complication with and without salvage reconstruction). Different subgroup analyses were done. RESULTS A total of 815 patients met inclusion criteria, with an overall median follow-up of 6.2 years. We found that there is no significant difference between prepectoral versus subpectoral for infection/necrosis (odds ratio [OR], 1.5; P = .3); capsular contracture (OR, 0.97; P = .9); absolute reconstruction failure (OR, 1.9; P = .12); and overall reconstruction failure (OR, 1.2; P = .5). Findings were confirmed using both logistic regression, time-to-event analysis, and multivariable analyses for the entire cohort and subgroups with and without PMRT. There was no significant difference between protons and photons in terms of infection/necrosis (OR, 1.6; P = .4) and absolute reconstruction failure (OR, 1.2; P = .7), but there were significantly higher risks for capsular contracture with protons (OR, 4.4; P < .001) and overall reconstruction failure compared with photons (OR, 2.0; P = .05). We did not find a significant correlation pattern between different dosimetry factors (the average dose, the maximum dose, and volume in cubic centimeter) in either the reconstructed chest wall target or the skin structure, about reconstruction complications, whether for proton or photon patients. CONCLUSIONS For patients receiving single-stage DTI reconstruction with and without PMRT, prepectoral implant placement had similar rates of complications and reconstruction failure compared with subpectoral reconstruction. Protons compared with photons did not increase the risk of infection/necrosis but significantly increased capsular contracture risks.
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Affiliation(s)
- George E Naoum
- Departments of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
| | - Hazim S Ababneh
- Departments of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
| | - Andrzej Niemierko
- Departments of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
| | - Laura Salama
- Departments of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
| | - Myrsini Ioannidou
- Departments of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
| | - Barbara L Smith
- Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
| | - Amy Colwell
- Plastic Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
| | - Alphonse G Taghian
- Departments of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
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Choi JI, Freedman GM, Guttmann DM, Ahmed K, Gao W, Walker EM, Harris EE, Gonzalez V, Ye J, Nead K, Taunk N, Tadros AB, Dang CT, Daroui P, Novick K. Executive Summary of the American Radium Society Appropriate Use Criteria: Regional Nodal Irradiation for Breast Cancer. Am J Clin Oncol 2025; 48:111-121. [PMID: 39761648 DOI: 10.1097/coc.0000000000001154] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/22/2025]
Abstract
OBJECTIVES Recent literature has provided additional data to further individualize treatment recommendations on regional nodal irradiation (RNI) patient selection and delivery techniques, but controversies surrounding optimal RNI utilization remain, including radiation technique, modality selection, and internal mammary lymph node (IMN) inclusion. The American Radium Society (ARS) Breast Appropriate Use Criteria (AUC) Committee performed a systematic review and developed a consensus guideline to summarize recent data and provide evidence-based recommendations. METHODS A multidisciplinary panel comprised of 15 members representing radiation oncologists, medical oncologists, and surgical oncologists specializing in the treatment of breast cancer conducted an analysis of the medical literature from January 1, 2011 to April 1, 2024. Modified Delphi methodology was used to rate the appropriateness of treatments for variants across 3 key questions. RESULTS Patients with intermediate-risk breast cancer, such as limited nodal involvement or large primary tumor size, are reasonable candidates for RNI, although a subset of patients with overall favorable clinicopathologic features may be considered for treatment de-escalation. Data on the use of advanced radiation techniques for RNI were limited in scope and strength, and the panel agreed that careful patient selection is needed when using these tools. Evidence suggests that the IMN should be included when delivering RNI given the absolute benefit demonstrated in multiple randomized trials. CONCLUSION A systematic review and evidence-based summary of recommendations are provided in these consensus guidelines from the ARS Breast AUC Committee to provide current comprehensive guidance on the optimal management of non-metastatic breast cancer patients being considered for RNI.
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Affiliation(s)
- J Isabelle Choi
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center and New York Proton Center, New York, NY
| | - Gary M Freedman
- Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
| | - David M Guttmann
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Kamran Ahmed
- Department of Radiation Oncology, Moffitt Cancer Center, Tampa, FL
| | - Wendy Gao
- Department of Radiation Oncology, Tacoma Valley Radiation Oncology Centers, Tacoma, WA
| | - Eleanor M Walker
- Department of Radiation Oncology, Henry Ford Health, Detroit, MI
| | - Eleanor E Harris
- Department of Radiation Oncology, St. Luke's University Health System, Easton, Philadelphia, PA
| | - Victor Gonzalez
- Department of Radiation Oncology, PeaceHealth St. Joseph Cancer Center, Bellingham, WA
| | - Jason Ye
- Department of Radiation Oncology, University of Southern California, Los Angeles, CA
| | - Kevin Nead
- Department of Radiation Oncology, MD Anderson Cancer Center, Houston, TX
| | - Neil Taunk
- Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
| | - Audree B Tadros
- Breast Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Chau T Dang
- Breast Cancer Medicine Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Parima Daroui
- Department of Radiation Oncology, City of Hope National Medical Center, Duarte, CA
| | - Kristina Novick
- Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA
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Costin IC, Marcu LG. Patient and treatment-related factors that influence dose to heart and heart substructures in left-sided breast cancer radiotherapy. Phys Med 2024; 128:104851. [PMID: 39504787 DOI: 10.1016/j.ejmp.2024.104851] [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: 06/12/2024] [Revised: 10/22/2024] [Accepted: 10/24/2024] [Indexed: 11/08/2024] Open
Abstract
BACKGROUND Cardiac substructures are critical organs at risk in left-sided breast cancer radiotherapy being often overlooked during treatment planning. The treatment technique plays an important role in diminishing dose to critical structures. This review aims to analyze the impact of treatment- and patient-related factors on heart substructure dosimetry and to identify the gaps in literature regarding dosimetric reporting of cardiac substructures. METHODS A systematic search of the literature was conducted in Medline/Pubmed database incorporating data published over the past 10 years, leading to 81 eligible studies. Treatment-related factors analyzed for their impact on patient outcome included the number of treatment fields, field geometry, treatment time and monitor units. Additionally, patient-related parameters such as breast size and tumor shape were considered for cardiac dosimetry evaluation. RESULTS Limited number of fields appeared to be an advantage for mean heart dose reduction when tangential IMRT versus multiple fields IMRT was evaluated. Larger breast size (910.20 ± 439.80 cm3) is linked to larger treatment fields and higher heart doses. Internal mammary node irradiation further escalates cardiac substructures dosimetry treated with 3DCRT and IMRT/VMAT. Proton therapy delivers lower mean heart dose regardless of breathing condition (free or respiratory-gated). CONCLUSION The management of treatment- and patient-related factors must be taken into account regardless of the treatment technique when evaluating cardiac dose. Furthermore, the gap found in the literature regarding heart toxicity assessment in left-sided breast cancer patients emphasizes the need for cardiac substructure contouring to better manage and control radiation-induced cardiac toxicities in this patient group.
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Affiliation(s)
- Ioana-Claudia Costin
- West University of Timisoara, Faculty of Physics, 300223, Timisoara, Romania; Emergency County Hospital, Oradea 410167, Romania
| | - Loredana G Marcu
- UniSA Allied Health and Human Performance, University of South Australia, Adelaide, SA 5001, Australia; Faculty of Informatics & Science, University of Oradea, Oradea 410087, Romania.
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Costin IC, Cinezan C, Marcu LG. Cardio-oncology concerns in radiotherapy: Heart and cardiac substructure toxicities from modern delivery techniques. Crit Rev Oncol Hematol 2024; 204:104538. [PMID: 39427839 DOI: 10.1016/j.critrevonc.2024.104538] [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: 07/27/2024] [Revised: 10/12/2024] [Accepted: 10/15/2024] [Indexed: 10/22/2024] Open
Abstract
Cardio-oncology is lately gaining more attention due to radiation-induced cardiac events reported by a very large number of studies. In view of this, the current overview of the literature aimed to encompass all studies from the past 15 years to assess changes in cardiac dose due to treatment evolution, as well as the changes in treatment planning customs to incorporate not only the heart as a whole but also cardiac substructures. Modern treatment techniques, particularly proton therapy, offers superior cardiac sparing compared to more established radiotherapy, for all evaluated tumor sites. Intensity modulation, particularly coupled with respiratory gating shows significant improvement in dose-volume parameters pertaining to the heart. While past studies considered mean heart dose as the only reference for cardiac toxicities, recommendations for the other cardiac substructures to be dosimetrically assessed during planning are becoming more common.
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Affiliation(s)
- Ioana-Claudia Costin
- West University of Timisoara, Faculty of Physics, Timisoara 300223, Romania; Clinical Emergency County Hospital Bihor, Oradea 410169, Romania
| | - Corina Cinezan
- Clinical Emergency County Hospital Bihor, Oradea 410169, Romania; Faculty of Medicine and Pharmacy, University of Oradea, Oradea 410087, Romania
| | - Loredana G Marcu
- Faculty of Informatics & Science, University of Oradea, Oradea 410087, Romania; UniSA Allied Health and Human Performance, University of South Australia, Adelaide, SA 5001, Australia.
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Qiao K, Wei Y, Tao C, Zhu J, Yuan S. Proton therapy for breast cancer: Reducing toxicity. Thorac Cancer 2024; 15:2156-2165. [PMID: 39275876 PMCID: PMC11496198 DOI: 10.1111/1759-7714.15451] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2024] [Revised: 08/25/2024] [Accepted: 09/03/2024] [Indexed: 09/16/2024] Open
Abstract
Radiotherapy is a crucial component in the holistic management of breast cancer, with approximately 60% of individuals diagnosed with breast cancer requiring this treatment. As the survival rate of individuals with breast cancer has significantly increased, there is a growing focus on the long-term well-being of patients. Proton therapy (PT) is a new and rapidly developing radiotherapy method. In comparison with conventional photon therapy, PT offers the benefits of decreased radiation toxicity and increased dosage in the designated region. This can extend patients' lifespan and enhance their overall well-being. The present analysis examines the function of PT in diminishing the harmful effects of radiation in cases of breast cancer, while also providing a brief overview of the future potential and obstacles associated with PT for breast cancer.
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Affiliation(s)
- Kailin Qiao
- Department of Radiation Oncology, Shanghai Pulmonary Hospital, School of MedicineTongji UniversityShanghaiChina
- Department of Radiation Oncology and Shandong Provincial Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and InstituteShandong First Medical University and Shandong Academy of Medical SciencesJinanChina
| | - Yuchun Wei
- Department of Radiation Oncology and Shandong Provincial Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and InstituteShandong First Medical University and Shandong Academy of Medical SciencesJinanChina
| | - Cheng Tao
- Department of Radiation Oncology Physics & Technology, Shandong Cancer Hospital and InstituteShandong First Medical University and Shandong Academy of Medical SciencesJinanChina
| | - Jian Zhu
- Department of Radiation Oncology Physics & Technology, Shandong Cancer Hospital and InstituteShandong First Medical University and Shandong Academy of Medical SciencesJinanChina
| | - Shuanghu Yuan
- Department of Radiation Oncology and Shandong Provincial Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and InstituteShandong First Medical University and Shandong Academy of Medical SciencesJinanChina
- Department of Radiation Oncology, The First Affiliated Hospital of USTC, Division of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiChina
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Choi JI, Hardy-Abeloos C, Lozano A, Hanlon A, Vargas C, Maduro JH, Bradley J, Offersen B, Haffty B, Pankuch M, Amos R, Kim N, MacDonald SM, Kirova Y, Mutter RW. PTCOG international survey of practice patterns and trends in utilization of proton therapy for breast cancer. Clin Transl Radiat Oncol 2024; 48:100847. [PMID: 39280125 PMCID: PMC11399555 DOI: 10.1016/j.ctro.2024.100847] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2024] [Revised: 08/21/2024] [Accepted: 08/22/2024] [Indexed: 09/18/2024] Open
Abstract
Purpose/objectives The indications, techniques, and extent to which proton beam therapy (PBT) is employed for breast cancer are unknown. We seek to determine PBT utilization for breast cancer. Materials/methods The Particle Therapy Co-Operative Group (PTCOG) Breast Subcommittee developed an IRB-approved 29-question survey and sent it to breast cancer radiation oncologists at all active PBT centers worldwide in June 2023. Descriptive statistics were used to summarize responses, and comparisons by continent were performed using Fisher's exact tests. Results Of 79 surveys distributed, 28 recipients submitted responses (35 % response rate) representing fifteen U.S., 8 European, and 5 Asian centers (continent response rate 50 %, 38 %, and 18 %, respectively). Overall, 93 % reported treating breast cancer patients with PBT; 13 (50 %) have treated ≥100 breast cancer patients at their center since opening. Most (89 %) have pencil beam scanning technology. Nearly half (46 %) use moderate hypofractionation (15-20 fractions) for regional nodal irradiation and 42 % conventional fractionation (25-30 fractions). More European centers prefer hypofractionation (88 %) vs. Asian (50 %) and U.S. (21 %) centers (p = 0.003). Common patient selection methods were practitioner determination/patient preference (n = 16) and comparative plan evaluation (n = 15). U.S. centers reported the most experience with breast PBT, with 71 % having treated ≥100 breast cancer patients vs. 38 % in Europe and none in Asia (p = 0.001). Of respondent centers, 39 % enrolled ≥75 % of breast PBT patients on a research study. Conclusion Utilization, patient selection methods, and dose-fractionation approaches for breast cancer PBT vary worldwide. These survey data serve as a benchmark from which successor surveys can provide insight on practice pattern evolution.
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Affiliation(s)
- J. Isabelle Choi
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
- New York Proton Center, New York, NY, USA
| | | | - Alicia Lozano
- Center for Biostatistics and Health Data Science, Department of Statistics, Virginia Tech, Roanoke, VA, USA
| | - Alexandra Hanlon
- Center for Biostatistics and Health Data Science, Department of Statistics, Virginia Tech, Roanoke, VA, USA
| | - Carlos Vargas
- Department of Radiation Oncology, Mayo Clinic, Phoenix, AZ, USA
| | - John H. Maduro
- Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Julie Bradley
- Department of Radiation Oncology, University of Florida, Jacksonville, FL, USA
| | - Birgitte Offersen
- Dept of Experimental Clinical Oncology, Dept Oncology, Danish Centre for Particle Therapy, Aarhus University Hospital, Denmark
| | - Bruce Haffty
- Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA
| | - Mark Pankuch
- Department of Medical Physics, Northwestern Medicine Proton Center, Warrenville, IL, USA
| | - Richard Amos
- Department of Medical Physics & Biomedical Engineering, University College London, London, UK
| | - Nalee Kim
- Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | | | - Youlia Kirova
- Department of Radiation Oncology, Institut Curie, Paris, France
| | - Robert W. Mutter
- Department of Radiation Oncology, Mayo Clinic, Rochester, MN, USA
- Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, USA
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Zhang H, Song D, Xie L, Zhan N, Xie W, Zhang J. Postmastectomy radiotherapy in breast reconstruction: Current controversies and trends. CANCER INNOVATION 2024; 3:e104. [PMID: 38948530 PMCID: PMC11212305 DOI: 10.1002/cai2.104] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 06/21/2023] [Revised: 09/11/2023] [Accepted: 09/13/2023] [Indexed: 07/02/2024]
Abstract
Breast cancer is the most common cancer among women worldwide. Postmastectomy radiotherapy (PMRT) is an essential component of combined therapy for early-stage, high-risk breast cancer. Breast reconstruction (BR) is often considered for patients with breast cancer who have undergone mastectomy. There has been a considerable amount of discussion about the optimal approach to combining PMRT with BR in the treatment of breast cancer. PMRT may increase the risk of complications and prevent good aesthetic results after BR, while BR may increase the complexity of PMRT and the radiation dose to surrounding normal tissues. The purpose of this review is to give a broad overview and summary of the current controversies and trends in PMRT and BR in the context of the most recent literature available.
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Affiliation(s)
- Honghong Zhang
- Department of Radiation Oncology, Xiang'an Hospital of Xiamen University, Cancer Research Center, School of MedicineXiamen University, Xiang'anXiamenFujianChina
| | - Dandan Song
- Department of Radiation Oncology, Xiang'an Hospital of Xiamen University, Cancer Research Center, School of MedicineXiamen University, Xiang'anXiamenFujianChina
| | - Liangxi Xie
- Department of Radiation Oncology, Xiang'an Hospital of Xiamen University, Cancer Research Center, School of MedicineXiamen University, Xiang'anXiamenFujianChina
| | - Ning Zhan
- Department of Radiation Oncology, Xiang'an Hospital of Xiamen University, Cancer Research Center, School of MedicineXiamen University, Xiang'anXiamenFujianChina
| | - Wenjia Xie
- Department of Radiation Oncology, Xiang'an Hospital of Xiamen University, Cancer Research Center, School of MedicineXiamen University, Xiang'anXiamenFujianChina
| | - Jianming Zhang
- Fujian Provincial Key Laboratory of Intelligent Identification and Control of Complex Dynamic System, Quanzhou Institute of Equipment Manufacturing, Haixi InstitutesChinese Academy of SciencesQuanzhouFujianChina
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Gao RW, Mullikin TC, Aziz KA, Afzal A, Smith NL, Routman DM, Gergelis KR, Harmsen WS, Remmes NB, Tseung HSWC, Shiraishi SS, Boughey JC, Ruddy KJ, Harless CA, Garda AE, Waddle MR, Park SS, Shumway DA, Corbin KS, Mutter RW. Postmastectomy Intensity Modulated Proton Therapy: 5-Year Oncologic and Patient-Reported Outcomes. Int J Radiat Oncol Biol Phys 2023; 117:846-856. [PMID: 37244627 DOI: 10.1016/j.ijrobp.2023.05.036] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2023] [Revised: 05/10/2023] [Accepted: 05/19/2023] [Indexed: 05/29/2023]
Abstract
PURPOSE To report oncologic, physician-assessed, and patient-reported outcomes (PROs) for a group of women homogeneously treated with modern, skin-sparing multifield optimized pencil-beam scanning proton (intensity modulated proton therapy [IMPT]) postmastectomy radiation therapy (PMRT). METHODS AND MATERIALS We reviewed consecutive patients who received unilateral, curative-intent, conventionally fractionated IMPT PMRT between 2015 and 2019. Strict constraints were applied to limit the dose to the skin and other organs at risk. Five-year oncologic outcomes were analyzed. Patient-reported outcomes were evaluated as part of a prospective registry at baseline, completion of PMRT, and 3 and 12 months after PMRT. RESULTS A total of 127 patients were included. One hundred nine (86%) received chemotherapy, among whom 82 (65%) received neoadjuvant chemotherapy. The median follow-up was 4.1 years. Five-year locoregional control was 98.4% (95% CI, 93.6-99.6), and overall survival was 87.9% (95% CI, 78.7-96.5). Acute grade 2 and 3 dermatitis was seen in 45% and 4% of patients, respectively. Three patients (2%) experienced acute grade 3 infection, all of whom had breast reconstruction. Three late grade 3 adverse events occurred: morphea (n = 1), infection (n = 1), and seroma (n = 1). There were no cardiac or pulmonary adverse events. Among the 73 patients at risk for PMRT-associated reconstruction complications, 7 (10%) experienced reconstruction failure. Ninety-five patients (75%) enrolled in the prospective PRO registry. The only metrics to increase by >1 point were skin color (mean change: 5) and itchiness (2) at treatment completion and tightness/pulling/stretching (2) and skin color (2) at 12 months. There was no significant change in the following PROs: bleeding/leaking fluid, blistering, telangiectasia, lifting, arm extension, or bending/straightening the arm. CONCLUSIONS With strict dose constraints to skin and organs at risk, postmastectomy IMPT was associated with excellent oncologic outcomes and PROs. Rates of skin, chest wall, and reconstruction complications compared favorably to previous proton and photon series. Postmastectomy IMPT warrants further investigation in a multi-institutional setting with careful attention to planning techniques.
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Affiliation(s)
- Robert W Gao
- Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota
| | - Trey C Mullikin
- Department of Radiation Oncology, Duke Cancer Center, Durham, North Carolina
| | - Khaled A Aziz
- Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota
| | - Arslan Afzal
- Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota
| | - Na L Smith
- Sanford Cancer Center, Sioux Falls, South Dakota
| | - David M Routman
- Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota
| | | | - William S Harmsen
- Department of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota
| | | | | | | | - Judy C Boughey
- Division of Breast and Melanoma Surgical Oncology, Mayo Clinic, Rochester, Minnesota
| | - Kathryn J Ruddy
- Division of Medical Oncology, Mayo Clinic, Rochester, Minnesota
| | | | - Allison E Garda
- Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota
| | - Mark R Waddle
- Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota
| | - Sean S Park
- Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota
| | - Dean A Shumway
- Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota
| | | | - Robert W Mutter
- Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota.
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11
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Lundstedt D, Lindberg A, Gustafsson M, Chakarova R, Karlsson P. Adjuvant Radiation Treatment of Breast Cancer After Mastectomy: Advanced Algorithms and Partial Bolus Improve the Dose Calculation Accuracy in the Case of Thin-Chest-Wall Irradiation. Adv Radiat Oncol 2023; 8:101223. [PMID: 37124029 PMCID: PMC10130603 DOI: 10.1016/j.adro.2023.101223] [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: 09/26/2022] [Accepted: 03/13/2023] [Indexed: 05/02/2023] Open
Abstract
Purpose The aim of this study was to examine measured and calculated dose distributions in a thin-chest-wall phantom and estimate the variations in the dose-volume histogram (DVH) parameters used in plan evaluation for patient geometries with chest-wall thicknesses <15 mm with and without bolus implementation. Methods and Materials Measurements were made using thermoluminescent dosimeters in a chest-wall phantom. The Monte Carlo method, anisotropic analytical algorithm, and Acuros XB Eclipse algorithms were used to calculate dose distributions for clinical plans. DVH parameters for clinical target volume tumor (CTVT) and planning target volume (PTV) and mean doses were evaluated for 15 patients with a chest-wall thickness of 8 to 15 mm with and without partial bolus and for 10 patients with a chest-wall thickness of 20 to 25 mm without bolus. Results Measurements showed that the dose at a depth of 2 to 12 mm at the beam entrance and laterally was within 90% of the dose at 8 mm depth. Monte Carlo and Acuros XB calculations were well aligned with the experimental data, whereas the anisotropic analytical algorithm underestimated the beam entrance and lateral doses. The DVH parameters for the patients with a thin chest wall were sensitive to calculation algorithm, resolution, body structure definition, and patient geometry. The parameters CTVTV95%, CTVTD98%, and PTVD98% were much lower than the tolerance criteria. Partial bolus improved the values for all algorithms and decreased the variations due to patient geometry. Dose calculations for patients with a chest-wall thickness of 20 to 25 mm resulted in sufficient target coverage and low dependence on patient geometry and calculation algorithm without the use of bolus. Conclusions Dose calculations using advanced algorithms and resolution <2 mm are recommended for patients with a thin chest wall. Specific DVH criteria or the implementation of partial bolus was needed to facilitate plan development and evaluation for this patient group.
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Affiliation(s)
- Dan Lundstedt
- Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Andreas Lindberg
- Department of Medical Physics and Biomedical Engineering, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Magnus Gustafsson
- Department of Medical Physics and Biomedical Engineering, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Roumiana Chakarova
- Department of Medical Physics and Biomedical Engineering, Sahlgrenska University Hospital, Gothenburg, Sweden
- Department of Medical Radiation Science, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Corresponding author: Roumiana Chakarova, PhD
| | - Per Karlsson
- Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy, Sahlgrenska University Hospital, Gothenburg, Sweden
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Ahmed SK, Keole SR. Proton Therapy in the Adolescent and Young Adult Population. Cancers (Basel) 2023; 15:4269. [PMID: 37686545 PMCID: PMC10487250 DOI: 10.3390/cancers15174269] [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: 07/06/2023] [Revised: 08/14/2023] [Accepted: 08/22/2023] [Indexed: 09/10/2023] Open
Abstract
BACKGROUND Adolescent and young adult cancer patients are at high risk of developing radiation-associated side effects after treatment. Proton beam radiation therapy might reduce the risk of these side effects for this population without compromising treatment efficacy. METHODS We review the current literature describing the utility of proton beam radiation therapy in the treatment of central nervous system tumors, sarcomas, breast cancer and Hodgkin lymphoma for the adolescent and young adult cancer population. RESULTS Proton beam radiation therapy has utility for the treatment of certain cancers in the young adult population. Preliminary data suggest reduced radiation dose to normal tissues, which might reduce radiation-associated toxicities. Research is ongoing to further establish the role of proton therapy in this population. CONCLUSION This report highlights the potential utility of proton beam radiation for certain adolescent young adult cancers, especially with reducing radiation doses to organs at risk and thereby potentially lowering risks of certain treatment-associated toxicities.
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Affiliation(s)
- Safia K. Ahmed
- Department of Radiation Oncology, Mayo Clinic Arizona, Phoenix, AZ 85054, USA;
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13
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Kirby AM, Holt F, Taylor CW, Haviland JS, MacKenzie M, Coles CE. Should patients requiring radiotherapy for breast cancer be treated with proton beam therapy? BMJ 2023; 381:e072896. [PMID: 37295798 DOI: 10.1136/bmj-2022-072896] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 06/12/2023]
Affiliation(s)
- Anna M Kirby
- Royal Marsden NHS Foundation Trust & Institute of Cancer Research, Sutton, UK
| | - Francesca Holt
- Nuffield Department of Population Health, University of Oxford, UK
| | - Carolyn W Taylor
- Nuffield Department of Population Health, University of Oxford, UK
| | - Joanne S Haviland
- Centre for Evaluation and Methods, Wolfson Institute of Population Health, Queen Mary University of London, UK
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Cui X, Jee K, Hu M, Bao J, Lu HM. Improvement of proton beam range uncertainty in breast treatment using tissue samples. Phys Med Biol 2022; 67. [PMID: 36379067 DOI: 10.1088/1361-6560/aca315] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2022] [Accepted: 11/15/2022] [Indexed: 11/16/2022]
Abstract
Objective.Proton therapy after breast-conserving surgery (BCS) can substantially reduce the dose to lung and cardiac structures. However, these dosimetric benefits are subject to beam range uncertainty in patient. The conversion of the CT-Hounsfield unit (HU) into relative stopping power (RSP) is the primary contribution to range uncertainty. Hence, an accurate HU-RSP conversion is essential.Approach.Real tissue samples, including muscle and adipose, were prepared. The water equivalent path length (WEPL) of these samples was measured under homogeneous conditions using a 12-diode detector array of our time-resolvedin vivorange verification system (IRVS). The HU-RSP conversion was improved using the measured WEPL and HU for adipose tissue. The measured WEPL values were compared with the treatment planning calculation results based on the stoichiometric CT-HU calibration technique. The effect was investigated for both with and without adipose tissue in HU-RSP conversion.Main results.The IRVS was calibrated based on the solid water phantom. The relative differences in WEPL (RSP) between measurements and calculations for muscle, adipose, and water was -1.19% (-0.75%), -4.25%(-4%), and -0.23%(-0.07%), respectively. Based on the improved HU-RSP conversion, the relative differences in WEPL was reduced to -0.97%(-0.62%), -1.50%(-1.46%), and -0.22% (0.00%), respectively.Significance.The WEPL deviation of adipose tissue is larger than the testing limit of 3.5% for beam range robustness in current clinical practice. However, the improved HU-RSP conversion reduced this deviation. The main component of breast tissue is adipose. Hence, the proton treatment of BCS can be undershooting if no proper measures are taken against this specific uncertainty.
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Affiliation(s)
- Xiangli Cui
- Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui, 230031, People's Republic of China.,Hefei Cancer Hospital, Chinese Academy of Sciences, Hefei, Anhui, 230031, People's Republic of China
| | - Kyungwook Jee
- Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, United States of America
| | - Man Hu
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, 250117, People's Republic of China
| | - Jie Bao
- Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui, 230031, People's Republic of China
| | - Hsiao-Ming Lu
- Hefei Ion Medical Center, Hefei, Anhui, 230088, People's Republic of China
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15
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Choi JI, Prabhu K, Hartsell WF, DeWees T, Sinesi C, Vargas C, Benda RK, Cahlon O, Chang AL. Outcomes and toxicities after proton partial breast radiotherapy for early stage, hormone receptor positive breast cancer: 3-Year results of a phase II multi-center trial. Clin Transl Radiat Oncol 2022; 37:71-77. [PMID: 36093343 PMCID: PMC9450061 DOI: 10.1016/j.ctro.2022.08.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2022] [Accepted: 08/24/2022] [Indexed: 12/04/2022] Open
Abstract
Purpose Proton therapy (PT) for partial breast irradiation (PBI) in early-stage breast cancer can decrease morbidity versus photon PBI with superior organs-at-risk sparing. We report 3-year outcomes of the first prospective, multicenter, phase II trial of proton PBI. Methods and Materials This Proton Collaborative Group phase II trial (PCG BRE007-12) recruited women ≥ 50 years with node-negative, estrogen receptor (ER)-positive, ≤3cm, invasive ductal carcinoma (IDC) or ductal carcinoma in situ undergoing breast conserving surgery followed by proton PBI (40 Gy(RBE), 10 daily fractions). Primary endpoint was freedom from ipsilateral breast cancer recurrence. Adverse events were prospectively graded using CTCAEv4.0. Breast Cancer Treatment Outcome Scale (BCTOS) assessed patient-reported quality of life (PRQOL). Results Thirty-eight evaluable patients enrolled between 2/2013-11/2016. Median age was 67 years (range 50-79); 55 % had left-sided disease, and median tumor size was 0.9 cm. Treatment was delivered in ≥ 2 fields predominantly with uniform scanning PT (n = 37). At 35-month median follow-up (12-62), all patients were alive, and none had local, regional or distant disease progression. One patient developed an ER-negative contralateral IDC. Seven grade 2 adverse events occurred; no radiotherapy-related grade ≥ 3 toxicities occurred. Changes in BCTOS subdomain mean scores were maximum 0.36, indicating no meaningful change in PRQOL. Median heart volume receiving 5 Gy (V5Gy), lung V20Gy, and lung V10Gy were 0 %, 0 % and 0.19 %, respectively. Conclusion At 3 years, proton PBI provided 100 % cancer control for early-stage, ER-positive breast cancer. Toxicities are minimal, and PRQOL remains acceptable with continued follow-up. These findings support PT as a safe and effective PBI delivery option.
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Affiliation(s)
- J. Isabelle Choi
- New York Proton Center, 225 East 126th Street, New York, NY 10035, USA
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10065, USA
| | - Kiran Prabhu
- Integris Health, 5911 W. Memorial, Oklahoma City, OK 73142, USA
| | - William F. Hartsell
- Northwestern Medicine, Chicago Proton Center, 4455 Weaver Pkwy, Warrenville, IL 60555, USA
| | - Todd DeWees
- Department of Quantitative Health Sciences, Mayo Clinic, 13400 E Shea Blvd, Scottsdale, AZ 85259, USA
| | - Christopher Sinesi
- Hampton University Proton Therapy Institute, 40 Enterprise Pkwy, Hampton, VA 23666, USA
| | - Carlos Vargas
- Department of Radiation Oncology, Mayo Clinic, 5777 E Mayo Blvd, Scottsdale, AZ 85054, USA
| | - Rashmi K. Benda
- Lynn Cancer Institute, Boca Raton Regional Hospital, 701 NW 13 St, Boca Raton, FL 33486, USA
| | - Oren Cahlon
- New York Proton Center, 225 East 126th Street, New York, NY 10035, USA
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10065, USA
| | - Andrew L. Chang
- California Protons Cancer Therapy Center, 9730 Summers Ridge Rd, San Diego, CA 92121, USA
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Lin H, Dong L, Jimenez RB. Emerging Technologies in Mitigating the Risks of Cardiac Toxicity From Breast Radiotherapy. Semin Radiat Oncol 2022; 32:270-281. [DOI: 10.1016/j.semradonc.2022.01.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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17
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Garda AE, Hunzeker AE, Michel AK, Fattahi S, Shiraishi S, Remmes NB, Schultz HL, Harmsen WS, Shumway DA, Yan ES, Park SS, Mutter RW, Corbin KS. Intensity Modulated Proton Therapy for Bilateral Breast or Chest Wall and Comprehensive Nodal Irradiation for Synchronous Bilateral Breast Cancer: Initial Clinical Experience and Dosimetric Comparison. Adv Radiat Oncol 2022; 7:100901. [PMID: 35647397 PMCID: PMC9133394 DOI: 10.1016/j.adro.2022.100901] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2021] [Accepted: 01/09/2022] [Indexed: 12/14/2022] Open
Abstract
Purpose Synchronous bilateral breast cancer (SBBC) poses distinct challenges for radiation therapy planning. We report our proton therapy experience in treating patients with SBBC. We also provide a dosimetric comparison of intensity modulated proton therapy (IMPT) versus photon therapy. Methods and Materials Patients with SBBC who received IMPT at our institution were retrospectively analyzed. The clinical target volume (CTV) included the breast or chest wall and comprehensive regional lymph nodes, including axilla, supraclavicular fossa, and the internal mammary chain. Intensity modulated proton therapy and volumetric modulated arc therapy (VMAT) plans were generated with the goal that 90% of the CTV would recieve at least 90% of the prescription dose (D90>=90%). Comparisons between modalities were made using the Wilcoxon signed rank test. Physician-reported acute toxic effects and photography were collected at baseline, end of treatment, and each follow-up visit. Results Between 2015 and 2018, 11 patients with SBBC were treated with IMPT. The prescription was 50 Gy in 25 fractions. The median CTV D90 was 99.9% for IMPT and 97.6% for VMAT (P = .001). The mean heart dose was 0.7 Gy versus 7.2 Gy (P = .001), the total lung mean dose was 7.8 Gy versus 17.3 Gy (P = .001), and the total lung volume recieving 20 Gy was 13.0% versus 27.4% (P = .001). The most common acute toxic effects were dermatitis (mostly grade 1-2 with 1 case of grade 3) and grade 1 to 2 fatigue. The most common toxic effects at the last-follow up (median, 32 months) were grade 1 skin hyperpigmentation, superficial fibrosis, and extremity lymphedema. No nondermatologic or nonfatigue adverse events of grade >1 were recorded. Conclusions Bilateral breast and/or chest wall and comprehensive nodal IMPT is technically feasible and associated with low rates of severe acute toxic effects. Treatment with IMPT offered improved target coverage and normal-tissue sparing compared with photon therapy. Long-term follow-up is ongoing to assess efficacy and toxic effects.
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Affiliation(s)
- Allison E. Garda
- Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota
| | | | - Ann K. Michel
- Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota
| | - Sayeh Fattahi
- Mayo Clinic Alix School of Medicine, Rochester, Minnesota
| | - Satomi Shiraishi
- Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota
| | | | | | - W. Scott Harmsen
- Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota
| | - Dean A. Shumway
- Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota
| | - Elizabeth S. Yan
- Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota
| | - Sean S. Park
- Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota
| | - Robert W. Mutter
- Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota
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18
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Reproducibility of Deep-Inspiration Breath Hold treatments on Halcyon™ performed using the first clinical version of AlignRT InBore™: results of CYBORE study. Clin Transl Radiat Oncol 2022; 35:90-96. [PMID: 35662884 PMCID: PMC9156859 DOI: 10.1016/j.ctro.2022.05.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2022] [Revised: 05/04/2022] [Accepted: 05/12/2022] [Indexed: 11/21/2022] Open
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19
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Proton therapy for the treatment of inflammatory breast cancer. Radiother Oncol 2022; 171:77-83. [DOI: 10.1016/j.radonc.2022.04.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2022] [Revised: 04/07/2022] [Accepted: 04/08/2022] [Indexed: 11/24/2022]
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20
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Oonsiri P, Nantavithya C, Lertbutsayanukul C, Sarsitthithum T, Vimolnoch M, Tawonwong T, Saksornchai K. Dosimetric evaluation of photons versus protons in postmastectomy planning for ultrahypofractionated breast radiotherapy. Radiat Oncol 2022; 17:20. [PMID: 35093111 PMCID: PMC8799967 DOI: 10.1186/s13014-022-01992-w] [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: 11/25/2021] [Accepted: 01/17/2022] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
Ultrahypofractionation can shorten the irradiation period. This study is the first dosimetric investigation comparing ultrahypofractionation using volumetric arc radiation therapy (VMAT) and intensity-modulated proton radiation therapy (IMPT) techniques in postmastectomy treatment planning.
Materials and methods
Twenty postmastectomy patients (10-left and 10-right sided) were replanned with both VMAT and IMPT techniques. There were four scenarios: left chest wall, left chest wall including regional nodes, right chest wall, and right chest wall including regional nodes. The prescribed dose was 26 Gy(RBE) in 5 fractions. For VMAT, a 1-cm bolus was added for 2 in 5 fractions. For IMPT, robust optimization was performed on the CTV structure with a 3-mm setup uncertainty and a 3.5% range uncertainty. This study aimed to compare the dosimetric parameters of the PTV, ipsilateral lung, contralateral lung, heart, skin, esophageal, and thyroid doses.
Results
The PTV-D95 was kept above 24.7 Gy(RBE) in both VMAT and IMPT plans. The ipsilateral lung mean dose of the IMPT plans was comparable to that of the VMAT plans. In three of four scenarios, the V5 of the ipsilateral lung in IMPT plans was lower than in VMAT plans. The Dmean and V5 of heart dose were reduced by a factor of 4 in the IMPT plans of the left side. For the right side, the Dmean of the heart was less than 1 Gy(RBE) for IMPT, while the VMAT delivered approximately 3 Gy(RBE). The IMPT plans showed a significantly higher skin dose owing to the lack of a skin-sparing effect in the proton beam. The IMPT plans provided lower esophageal and thyroid mean dose.
Conclusion
Despite the higher skin dose with the proton plan, IMPT significantly reduced the dose to adjacent organs at risk, which might translate into the reduction of late toxicities when compared with the photon plan.
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21
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Bachir B, Anouti S, Abi Jaoude J, Kayali M, Tfayli A, de Azambuja E, Poortmans P, Zeidan YH. Evaluation of Cardiotoxicity in HER-2-Positive Breast Cancer Patients Treated With Radiation Therapy and Trastuzumab. Int J Radiat Oncol Biol Phys 2022; 113:135-142. [PMID: 34986381 DOI: 10.1016/j.ijrobp.2021.12.159] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Revised: 12/22/2021] [Accepted: 12/23/2021] [Indexed: 12/23/2022]
Abstract
PURPOSE Trastuzumab is associated with cardiac dysfunction in patients with human epidermal growth factor receptor 2 (HER-2)-positive breast cancer. The current study examines the effect of radiation therapy (RT) on cardiotoxicity in this patient population. METHODS AND MATERIALS The Herceptin Adjuvant (HERA) trial is a phase 3 prospective, randomized clinical trial that established the efficacy of trastuzumab in HER-2-positive breast cancer. The current study is a retrospective analysis of 3321 trial patients treated with trastuzumab, with or without RT. Cardiac function was closely monitored over a median follow-up period of 11 years. The primary endpoint of the current study was to determine the effect of RT on left ventricular ejection fraction (LVEF) and the occurrence of cardiovascular events. RESULTS Patients were divided into 3 groups: 1270 patients received trastuzumab and left-sided RT (group 1); 1271 patients received trastuzumab and right-sided RT (group 2); and 780 patients received trastuzumab with no RT (group 3). The incidence of decline in LVEF documented by echocardiography was 9.18%, 8.99%, and 8.80%, respectively, with no significant differences among the 3 groups (P = .073). The incidence of cardiovascular events was low in all groups, with the lowest incidence noted in group 3 (0.62%) followed by group 2 (0.92%) and group 1 (1.08%) (P = .619). Univariate and multivariate competing-risks regression showed that left-sided and right-sided RT delivery did not significantly increase the risk of LVEF decline or cardiovascular events. CONCLUSIONS Our analysis of the HERA trial suggests that RT does not significantly increase the risk of cardiotoxicity in HER-2-positive breast cancer patients treated with trastuzumab. Continued monitoring of patients is needed to investigate late effects of contemporary treatments for breast cancer patients.
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Affiliation(s)
- Bachir Bachir
- American University of Beirut Medical Center, Beirut, Lebanon
| | - Sirine Anouti
- American University of Beirut, Faculty of Health Sciences, Beirut, Lebanon
| | | | - Majd Kayali
- American University of Beirut Medical Center, Beirut, Lebanon
| | - Arafat Tfayli
- American University of Beirut Medical Center, Beirut, Lebanon
| | - Evandro de Azambuja
- Institut Jules Bordet and l'Université Libre de Bruxelles (ULB), Brussels, Belgium
| | - Philip Poortmans
- Iridium Netwerk, Wilrijk-Antwerp, Belgium; University of Antwerp, Faculty of Medicine and Health Sciences, Wilrijk-Antwerp, Belgium
| | - Youssef H Zeidan
- Lynn Cancer Institute, Baptist Health South Florida, Boca Raton, FL.
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22
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Boersma L, Sattler M, Maduro J, Bijker N, Essers M, van Gestel C, Klaver Y, Petoukhova A, Rodrigues M, Russell N, van der Schaaf A, Verhoeven K, van Vulpen M, Schuit E, Langendijk J. Model-Based Selection for Proton Therapy in Breast Cancer: Development of the National Indication Protocol for Proton Therapy and First Clinical Experiences. Clin Oncol (R Coll Radiol) 2022; 34:247-257. [DOI: 10.1016/j.clon.2021.12.007] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2021] [Revised: 10/11/2021] [Accepted: 12/10/2021] [Indexed: 12/20/2022]
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Choi JI, Khan AJ, Powell SN, McCormick B, Lozano AJ, Del Rosario G, Mamary J, Liu H, Fox P, Gillespie E, Braunstein LZ, Mah D, Cahlon O. Proton reirradiation for recurrent or new primary breast cancer in the setting of prior breast irradiation. Radiother Oncol 2021; 165:142-151. [PMID: 34688807 DOI: 10.1016/j.radonc.2021.10.010] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2021] [Revised: 10/07/2021] [Accepted: 10/11/2021] [Indexed: 12/25/2022]
Abstract
BACKGROUND AND PURPOSE Late local recurrences and second primary breast cancers are increasingly common. Proton beam therapy (PBT) reirradiation (reRT) may allow safer delivery of a second definitive radiotherapy (RT) course. We analyzed outcomes of patients with recurrent or new primary breast cancer who underwent reRT. MATERIALS AND METHODS In an IRB-approved retrospective study, patient/tumor characteristics, treatment parameters, outcomes, and toxicities were collected for all consecutive patients with recurrent or new primary non-metastatic breast cancer previously treated with breast or chest wall RT who underwent PBT reRT. RESULTS Forty-six patients received reRT using uniform (70%) or pencil beam (30%) scanning PBT. Median first RT, reRT, and cumulative doses were 60 Gy (range 45-66 Gy), 50.4 Gy(RBE) (40-66.6 Gy(RBE)), and 110 Gy(RBE) (96.6-169.4 Gy(RBE)), respectively. Median follow-up was 21 months. There were no local or regional recurrences; 17% developed distant recurrence. Two-year DMFS and OS were 92.0% and 93.6%, respectively. Nine of 13 (69.2%) patients who underwent implant or flap reconstruction developed capsular contracture, 3 (23.1%) requiring surgical intervention. One (7.7%) patient developed grade 3 breast pain requiring mastectomy after breast conserving surgery. No acute or late grade 4-5 toxicities were seen. Increased body mass index (BMI) was protective of grade ≥ 2 acute toxicity (OR = 0.84, 95%CI = 0.70-1.00). CONCLUSION In the largest series to date of PBT reRT for breast cancer recurrence or new primary after prior definitive breast or chest wall RT, excellent locoregional control and few high-grade toxicities were encountered. PBT reRT may provide a relatively safe and highly effective salvage option. Additional patients and follow-up are needed to correlate composite normal tissue doses with toxicities and assess long-term outcomes.
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Affiliation(s)
- J Isabelle Choi
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, USA; New York Proton Center, New York, USA.
| | - Atif J Khan
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, USA
| | - Simon N Powell
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, USA
| | - Beryl McCormick
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, USA
| | | | | | | | - Haoyang Liu
- ProCure Proton Therapy Center, Somerset, USA
| | - Pamela Fox
- ProCure Proton Therapy Center, Somerset, USA
| | - Erin Gillespie
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, USA
| | - Lior Z Braunstein
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, USA
| | - Dennis Mah
- ProCure Proton Therapy Center, Somerset, USA
| | - Oren Cahlon
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, USA; New York Proton Center, New York, USA
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Mutter RW, Choi JI, Jimenez RB, Kirova YM, Fagundes M, Haffty BG, Amos RA, Bradley JA, Chen PY, Ding X, Carr AM, Taylor LM, Pankuch M, Vega RBM, Ho AY, Nyström PW, McGee LA, Urbanic JJ, Cahlon O, Maduro JH, MacDonald SM. Proton Therapy for Breast Cancer: A Consensus Statement From the Particle Therapy Cooperative Group Breast Cancer Subcommittee. Int J Radiat Oncol Biol Phys 2021; 111:337-359. [PMID: 34048815 PMCID: PMC8416711 DOI: 10.1016/j.ijrobp.2021.05.110] [Citation(s) in RCA: 52] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2020] [Revised: 05/12/2021] [Accepted: 05/17/2021] [Indexed: 12/23/2022]
Abstract
Radiation therapy plays an important role in the multidisciplinary management of breast cancer. Recent years have seen improvements in breast cancer survival and a greater appreciation of potential long-term morbidity associated with the dose and volume of irradiated organs. Proton therapy reduces the dose to nontarget structures while optimizing target coverage. However, there remain additional financial costs associated with proton therapy, despite reductions over time, and studies have yet to demonstrate that protons improve upon the treatment outcomes achieved with photon radiation therapy. There remains considerable heterogeneity in proton patient selection and techniques, and the rapid technological advances in the field have the potential to affect evidence evaluation, given the long latency period for breast cancer radiation therapy recurrence and late effects. In this consensus statement, we assess the data available to the radiation oncology community of proton therapy for breast cancer, provide expert consensus recommendations on indications and technique, and highlight ongoing trials' cost-effectiveness analyses and key areas for future research.
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Affiliation(s)
- Robert W Mutter
- Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota.
| | - J Isabelle Choi
- Department of Radiation Oncology, New York Proton Center and Memorial Sloan Kettering Cancer Center, New York, New York
| | - Rachel B Jimenez
- Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts
| | - Youlia M Kirova
- Department of Radiation Oncology, Institut Curie, Paris, France
| | - Marcio Fagundes
- Department of Radiation Oncology, Miami Cancer Institute, Miami, Florida
| | - Bruce G Haffty
- Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey
| | - Richard A Amos
- Proton and Advanced Radiotherapy Group, Department of Medical Physics and Biomedical Engineering, University College London, London, United Kingdom
| | - Julie A Bradley
- Department of Radiation Oncology, University of Florida, Jacksonville, Florida
| | - Peter Y Chen
- Department of Radiation Oncology, Beaumont Health, Royal Oak, Michigan
| | - Xuanfeng Ding
- Department of Radiation Oncology, Beaumont Health, Royal Oak, Michigan
| | - Antoinette M Carr
- Department of Radiation Oncology, Beaumont Health, Royal Oak, Michigan
| | - Leslie M Taylor
- Department of Radiation Oncology, Beaumont Health, Royal Oak, Michigan
| | - Mark Pankuch
- Department of Radiation Oncology, Northwestern Medicine Proton Center, Warrenville, Illinois
| | | | - Alice Y Ho
- Department of Radiation Oncology, New York Proton Center and Memorial Sloan Kettering Cancer Center, New York, New York
| | - Petra Witt Nyström
- The Skandion Clinic, Uppsala, Sweden and the Danish Centre for Particle Therapy, Aarhus, Denmark
| | - Lisa A McGee
- Department of Radiation Oncology, Mayo Clinic Hospital, Phoenix, Arizona
| | - James J Urbanic
- Department of Radiation Medicine and Applied Sciences, UC San Diego Health, Encinitas, California
| | - Oren Cahlon
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York
| | - John H Maduro
- Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Shannon M MacDonald
- Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts
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DeCesaris CM, Mossahebi S, Jatczak J, Rao AD, Zhu M, Mishra MV, Nichols E. Outcomes of and treatment planning considerations for a hybrid technique delivering proton pencil-beam scanning radiation to women with metal-containing tissue expanders undergoing post-mastectomy radiation. Radiother Oncol 2021; 164:289-298. [PMID: 34280402 DOI: 10.1016/j.radonc.2021.07.012] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2021] [Revised: 07/06/2021] [Accepted: 07/08/2021] [Indexed: 11/20/2022]
Abstract
BACKGROUND Following mastectomy, immediate breast reconstruction often involves the use of temporary tissue expanders (TEs). TEs contain metallic ports (MPs), which complicate proton pencil-beam scanning (PBS) planning. A technique was implemented for delivering PBS post-mastectomy radiation (PMRT) to patients with TEs and MPs. METHODS A protocol utilizing a hybrid single- and multi-field optimization (SFO, MFO) technique was developed. Plans were robustly optimized using a Monte Carlo algorithm. A CTV_eval structure including chest wall (CW) and regional nodal (RNI) targets and excluding the TE was evaluated. Organ at risk (OAR) dosimetry and acute toxicities were analyzed. RESULTS Twenty-nine women were treated with this technique. A 2-field SFO technique was used superior and inferior to the MP, with a 3 or 4-field MFO technique used at the level of the MP. Virtual blocks were utilized so that beams did not travel through the MP. A port-to-CW distance of 1 cm was required. Patients underwent daily image-guidance to ensure the port remained within a 0.5 cm internal planning volume (ITV). Median RT dose to CTV_eval was 50.4 Gy (45.0-50.4). Median 95% CTV_eval coverage was 99.5% (95-100). Optically stimulated luminescent dosimeter (OSLD) readings were available for 8 patients and correlated to the dose measurements in the treatment planning system (TPS); median OSLD ratio was 0.99 (range, 0.93-1.02). CONCLUSIONS Delivering PMRT with PBS for women with metal-containing TEs using a hybrid SFO/MFO technique is feasible, reproducible, and achieves excellent dose distributions. Specialized planning and image-guidance techniques are required to safely utilize this treatment in the clinic.
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Affiliation(s)
- Cristina M DeCesaris
- Department of Radiation Oncology, University of Maryland Medical Center, Baltimore, United States.
| | - Sina Mossahebi
- Division of Physics, Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, United States
| | - Jenna Jatczak
- Maryland Proton Treatment Center, Baltimore, United States
| | - Avani D Rao
- Department of Radiation Oncology, Inova Schar Cancer Institute, Fairfax, United States
| | - Mingyao Zhu
- Department of Radiation Oncology, Emory University, Atlanta, United States
| | - Mark V Mishra
- Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, United States
| | - Elizabeth Nichols
- Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, United States
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Leduc A, Chaouni S, Pouzoulet F, De Marzi L, Megnin-Chanet F, Corre E, Stefan D, Habrand JL, Sichel F, Laurent C. Differential normal skin transcriptomic response in total body irradiated mice exposed to scattered versus scanned proton beams. Sci Rep 2021; 11:5876. [PMID: 33712719 PMCID: PMC7955113 DOI: 10.1038/s41598-021-85394-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2020] [Accepted: 02/10/2021] [Indexed: 12/13/2022] Open
Abstract
Proton therapy allows to avoid excess radiation dose on normal tissues. However, there are some limitations. Indeed, passive delivery of proton beams results in an increase in the lateral dose upstream of the tumor and active scanning leads to strong differences in dose delivery. This study aims to assess possible differences in the transcriptomic response of skin in C57BL/6 mice after TBI irradiation by active or passive proton beams at the dose of 6 Gy compared to unirradiated mice. In that purpose, total RNA was extracted from skin samples 3 months after irradiation and RNA-Seq was performed. Results showed that active and passive delivery lead to completely different transcription profiles. Indeed, 140 and 167 genes were differentially expressed after active and passive scanning compared to unirradiated, respectively, with only one common gene corresponding to RIKEN cDNA 9930021J03. Moreover, protein-protein interactions performed by STRING analysis showed that 31 and 25 genes are functionally related after active and passive delivery, respectively, with no common gene between both types of proton delivery. Analysis showed that active scanning led to the regulation of genes involved in skin development which was not the case with passive delivery. Moreover, 14 ncRNA were differentially regulated after active scanning against none for passive delivery. Active scanning led to 49 potential mRNA-ncRNA pairs with one ncRNA mainly involved, Gm44383 which is a miRNA. The 43 genes potentially regulated by the miRNA Gm44393 confirmed an important role of active scanning on skin keratin pathway. Our results demonstrated that there are differences in skin gene expression still 3 months after proton irradiation versus unirradiated mouse skin. And strong differences do exist in late skin gene expression between scattered or scanned proton beams. Further investigations are strongly needed to understand this discrepancy and to improve treatments by proton therapy.
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Affiliation(s)
- Alexandre Leduc
- Normandie Univ, UNICAEN, UNIROUEN, ABTE-EA4651, ToxEMAC, Cancer Centre François Baclesse, 14000, Caen, France
| | - Samia Chaouni
- Normandie Univ, UNICAEN, UNIROUEN, ABTE-EA4651, ToxEMAC, Cancer Centre François Baclesse, 14000, Caen, France
| | - Frédéric Pouzoulet
- Institut Curie, RadeXp Platform, centre universitaire, 91405, Orsay, France
| | - Ludovic De Marzi
- Institut Curie, PSL Research University, University Paris Saclay, Laboratoire d'Imagerie Translationnelle en Oncologie, INSERM, 91401, Orsay, France
- Institut Curie, PSL Research University, Radiation Oncology Department, Proton Therapy Centre, Centre Universitaire, 91898, Orsay, France
| | - Frédérique Megnin-Chanet
- INSERM U1196/UMR9187 CMIB, University Paris-Saclay, Institut Curie-Recherche, bât. 112, rue H. Becquerel, 91405, Orsay, France
| | - Erwan Corre
- CNRS, Sorbonne Université, R2424, ABiMS platform, Station Biologique, 29680, Roscoff, France
| | - Dinu Stefan
- Normandie Univ, UNICAEN, UNIROUEN, ABTE-EA4651, ToxEMAC, Cancer Centre François Baclesse, 14000, Caen, France
- Radiotherapy Department, Cancer Centre François Baclesse, 14000, Caen, France
| | - Jean-Louis Habrand
- Normandie Univ, UNICAEN, UNIROUEN, ABTE-EA4651, ToxEMAC, Cancer Centre François Baclesse, 14000, Caen, France
- Radiotherapy Department, Cancer Centre François Baclesse, 14000, Caen, France
| | - François Sichel
- Normandie Univ, UNICAEN, UNIROUEN, ABTE-EA4651, ToxEMAC, Cancer Centre François Baclesse, 14000, Caen, France
| | - Carine Laurent
- Normandie Univ, UNICAEN, UNIROUEN, ABTE-EA4651, ToxEMAC, Cancer Centre François Baclesse, 14000, Caen, France.
- SAPHYN/ARCHADE (Advanced Resource Centre for HADrontherapy in Europe), Cancer Centre François Baclesse, 14000, Caen, France.
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Biological Effects of Scattered Versus Scanned Proton Beams on Normal Tissues in Total Body Irradiated Mice: Survival, Genotoxicity, Oxidative Stress and Inflammation. Antioxidants (Basel) 2020; 9:antiox9121170. [PMID: 33255388 PMCID: PMC7761103 DOI: 10.3390/antiox9121170] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2020] [Revised: 11/16/2020] [Accepted: 11/18/2020] [Indexed: 02/06/2023] Open
Abstract
Side effects of proton therapy are poorly studied. Moreover, the differences in the method of dose delivery on normal tissues are not taken into account when proton beams are scanned instead of being scattered. We proposed here to study the effects of both modalities of proton beam delivery on blood; skin; lung and heart in a murine model. In that purpose; C57BL/6 mice were total body irradiated by 190.6 MeV proton beams either by Double Scattering (DS) or by Pencil Beam Scanning (PBS) in the plateau phase before the Bragg Peak. Mouse survival was evaluated. Blood and organs were removed three months after irradiation. Biomarkers of genotoxicity; oxidative stress and inflammation were measured. Proton irradiation was shown to increase lymphocyte micronucleus frequency; lung superoxide dismutase activity; erythrocyte and skin glutathione peroxidase activity; erythrocyte catalase activity; lung; heart and skin oxidized glutathione level; erythrocyte and lung lipid peroxidation and erythrocyte protein carbonylation even 3 months post-irradiation. When comparing both methods of proton beam delivery; mouse survival was not different. However, PBS significantly increased lymphocyte micronucleus frequency; erythrocyte glutathione peroxidase activity and heart oxidized glutathione level compared to DS. These results point out the necessity to take into account the way of delivering dose in PT as it could influence late side effects.
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Assessing the Need for Adjusted Organ-at-Risk Planning Goals for Patients Undergoing Adjuvant Radiation Therapy for Locally Advanced Breast Cancer with Proton Radiation. Pract Radiat Oncol 2020; 11:108-118. [PMID: 33109494 DOI: 10.1016/j.prro.2020.09.003] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2020] [Revised: 08/25/2020] [Accepted: 09/04/2020] [Indexed: 12/22/2022]
Abstract
PURPOSE Locally advanced breast cancer requires surgical management via lumpectomy or mastectomy with or without systemic therapy followed by chest wall or breast (CW) and comprehensive nodal irradiation (CNI). Radiation (RT) dose constraints for the heart and ipsilateral lung have been developed based on photon RT. Proton therapy (PBT) can deliver significantly lower doses of RT to these organs-at-risk (OARs) and may warrant adjustments to OAR planning goals. METHODS AND MATERIALS The RT plans of consecutive patients undergoing adjuvant CW-CNI RT with PBT within a single center were reviewed. A inital treatment volume, comprised of CW/intact breast + CNI (CTV_init) structure, including the CW and CNI but excluding any boost plans was analyzed. Frequency distributions were generated based on doses received by the heart, lungs, and esophagus for validated dosimetric parameters. Frequency distributions were generated and then stratified by laterality and compared using the Kruskal-Wallis H test. The 75th, 85th, and 95th percentiles for each dosimetric parameter were calculated, overall and by laterality. The 75th percentile (Q3), was used as a suggested primary goal, and the 95th percentile was used as a suggested secondary goal. RESULTS One hundred and seventy-two plans were analyzed. Forty-nine plans were right-sided, 107 were left-sided, and 16 were bilateral. The overall Q3 of the mean and V25 of the heart were 1.5 Gy and 1.7%, respectively. The mean and V25 to the heart differed significantly by laterality. Pulmonary values were similar to current recommendations. For all lateralites, the median volume of the esophagus receiving 70% prescription dose was ≤1 cm3. CONCLUSIONS We present the first dosimetric study providing complete OAR dose-volume histograms data for patients undergoing adjuvant pencil-beam scanning-PBT for locally advanced breast cancer, with detailed information on central tendencies, ranges and distributions of data. We have provided suggested planning goals and metrics for the lungs, heart, and esophagus; the latter 2 differing significantly from current Quantitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC) constraints and classical photon goals.
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Torres MA, Horst KC, Freedman GM. Postmastectomy and Regional Nodal Radiation for Breast Cancer. J Clin Oncol 2020; 38:2299-2309. [PMID: 32442076 DOI: 10.1200/jco.19.02908] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Affiliation(s)
- Mylin A Torres
- Department of Radiation Oncology, Glenn Family Breast Center, Winship Cancer Institute, Emory University, Atlanta, GA
| | - Kathleen C Horst
- Department of Radiation Oncology, Stanford Cancer Institute, Stanford University, Stanford, CA
| | - Gary M Freedman
- Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
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Kowalski ES, Feigenberg SJ, Cohen J, Fellows Z, Vadnais P, Rice S, Mishra MV, Molitoris JK, Nichols EM, Snider JW. Optimal Target Delineation and Treatment Techniques in the Era of Conformal Photon and Proton Breast and Regional Nodal Irradiation. Pract Radiat Oncol 2020; 10:174-182. [DOI: 10.1016/j.prro.2019.11.010] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2019] [Revised: 10/27/2019] [Accepted: 11/14/2019] [Indexed: 12/16/2022]
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Practical Heart Sparing Breast Cancer Radiation Therapy Using Continuous Positive Airway Pressure (CPAP) in Resource-Limited Radiation Oncology Clinics. Am J Clin Oncol 2020; 42:797-801. [PMID: 31503062 DOI: 10.1097/coc.0000000000000597] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
PURPOSE The purpose of this study was to report experiences of practical heart sparing breast radiation therapy (RT) using continuous positive airway pressure (CPAP) in resource-limited radiation oncology clinics. PATIENTS AND METHODS Twelve patients underwent computed tomography-simulations with both free-breathing (FB) and CPAP under the individual maximum tolerable air pressure. For each patient, left-sided breast RT plans (9 with breast only, 3 with breast and regional nodal stations) with FB and CPAP were created using 3-dimensional conformal RT (supine tangential or wide tangential RT fields) according to RTOG 1304. For daily RT, patients started CPAP in the patients waiting area for 15 minutes before entering the treatment room and continued CPAP during RT. Treatment setup times between breast RT with and without CPAP were compared. RESULTS All patients tolerated CPAP well with 8 to 15 cm H2O of air pressure. Compared with FB, CPAP inflated the thorax and increased total lung volume by 35±16% (CPAP: 3136±751 vs. FB: 2354±657 cm, P<0.01); caudally displaced the heart by 1.8 cm (P<0.01); and decreased heart volume within tangential RT fields on computed tomography-simulation scans by 96±4% (1.4±2.5 vs. 21±17 cm, P=0.02) in all patients. Planning target volume coverage was acceptable in all RT plans. CPAP lowered mean dose (Dmean) to heart by 47±22% (2.5±1.5 vs. 5.4±3.3 Gy, P<0.01); heart volume receiving ≥25 Gy (V25) by 82±18% (2.2±2.6 vs. 9.1±7.1%, P<0.01); Dmean to left anterior descending coronary artery by 68±8% (4.7±1.9 vs. 14.8±3.3 Gy, P<0.01). CPAP decreased radiation dose to ipsilateral lung compared with FB: 9.1±5.8 versus 11.2±8 Gy (20% reduction, P=0.03) of Dmean; 15.7±12.5 vs. 20.5±17.5% (25% reduction, P=0.03) of V20. RT with CPAP did not increase treatment setup time compared with FB (week 1: 362±63 vs. 352±77 s; week 2 to 5: 217±13 vs. 201±14 s, all P>0.25). CONCLUSION Novel use of CPAP allowed efficient and practical heart sparing breast RT without increasing infrastructural requirements in resource-limited radiation oncology clinics.
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Joste M, Arsene‐Henry A, Reyal F, Amessis M, Fourquet A, Kirova YM. Helical tomotherapy for patients presented with implant breast reconstruction in case of adjuvant breast cancer radiotherapy: A single center experience. Breast J 2019; 26:1436-1438. [DOI: 10.1111/tbj.13687] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2019] [Revised: 10/17/2019] [Accepted: 10/18/2019] [Indexed: 11/28/2022]
Affiliation(s)
- Marine Joste
- Department of Radiation Oncology Institut Curie Paris France
| | | | - Fabien Reyal
- Department of Surgical Oncology Institut Curie Paris France
- University Paris V Paris France
| | - Malika Amessis
- Department of Radiation Oncology Institut Curie Paris France
| | - Alain Fourquet
- Department of Radiation Oncology Institut Curie Paris France
| | - Youlia M. Kirova
- Department of Radiation Oncology Institut Curie Paris France
- University Versailles Saint Quentin Saint-Quentin en Yvelines France
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Yuan TZ, Zhan ZJ, Qian CN. New frontiers in proton therapy: applications in cancers. Cancer Commun (Lond) 2019; 39:61. [PMID: 31640788 PMCID: PMC6805548 DOI: 10.1186/s40880-019-0407-3] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2019] [Accepted: 10/11/2019] [Indexed: 12/11/2022] Open
Abstract
Proton therapy offers dominant advantages over photon therapy due to the unique depth-dose characteristics of proton, which can cause a dramatic reduction in normal tissue doses both distal and proximal to the tumor target volume. In turn, this feature may allow dose escalation to the tumor target volume while sparing the tumor-neighboring susceptible organs at risk, which has the potential to reduce treatment toxicity and improve local control rate, quality of life and survival. Some dosimetric studies in various cancers have demonstrated the advantages over photon therapy in dose distributions. Further, it has been observed that proton therapy confers to substantial clinical advantage over photon therapy in head and neck, breast, hepatocellular, and non-small cell lung cancers. As such, proton therapy is regarded as the standard modality of radiotherapy in many pediatric cancers from the technical point of view. However, due to the limited clinical evidence, there have been concerns about the high cost of proton therapy from an economic point of view. Considering the treatment expenses for late radiation-induced toxicities, cost-effective analysis in many studies have shown that proton therapy is the most cost-effective option for brain, head and neck and selected breast cancers. Additional studies are warranted to better unveil the cost-effective values of proton therapy and to develop newer ways for better protection of normal tissues. This review aims at reviewing the recent studies on proton therapy to explore its benefits and cost-effectiveness in cancers. We strongly believe that proton therapy will be a common radiotherapy modality for most types of solid cancers in the future.
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Affiliation(s)
- Tai-Ze Yuan
- Department of Radiation Oncology, Guangzhou Concord Cancer Center, Guangzhou, 510045, Guangdong, P. R. China
| | - Ze-Jiang Zhan
- Department of Radiation Oncology, Cancer Center of Guangzhou Medical University, Guangzhou, 510095, Guangdong, P. R. China
| | - Chao-Nan Qian
- Department of Radiation Oncology, Guangzhou Concord Cancer Center, Guangzhou, 510045, Guangdong, P. R. China.
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Jimenez RB, Hickey S, DePauw N, Yeap BY, Batin E, Gadd MA, Specht M, Isakoff SJ, Smith BL, Liao EC, Colwell AS, Ho A, Januzzi JL, Passeri J, Neilan TG, Taghian AG, Lu HM, MacDonald SM. Phase II Study of Proton Beam Radiation Therapy for Patients With Breast Cancer Requiring Regional Nodal Irradiation. J Clin Oncol 2019; 37:2778-2785. [PMID: 31449469 PMCID: PMC7351324 DOI: 10.1200/jco.18.02366] [Citation(s) in RCA: 65] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/23/2019] [Indexed: 01/04/2023] Open
Abstract
PURPOSE To evaluate the safety and efficacy of proton beam radiation therapy (RT) for patients with breast cancer who require regional nodal irradiation. METHODS Patients with nonmetastatic breast cancer who required postoperative RT to the breast/chest wall and regional lymphatics and who were considered suboptimal candidates for conventional RT were eligible. The primary end point was the incidence of grade 3 or higher radiation pneumonitis (RP) or any grade 4 toxicity within 3 months of RT. Secondary end points were 5-year locoregional failure, overall survival, and acute and late toxicities per Common Terminology Criteria for Adverse Events (version 4.0). Strain echocardiography and cardiac biomarkers were obtained before and after RT to assess early cardiac changes. RESULTS Seventy patients completed RT between 2011 and 2016. Median follow-up was 55 months (range, 17 to 82 months). Of 69 evaluable patients, median age was 45 years (range, 24 to 70 years). Sixty-three patients (91%) had left-sided breast cancer, two had bilateral breast cancer, and five had right-sided breast cancer. Sixty-five (94%) had stage II to III breast cancer. Sixty-eight (99%) received systemic chemotherapy. Fifty (72%) underwent immediate reconstruction. Median dose to the chest wall/breast was 49.7 Gy (relative biological effectiveness) and to the internal mammary nodes, 48.8 Gy (relative biological effectiveness), which indicates comprehensive coverage. Among 62 surviving patients, the 5-year rates for locoregional failure and overall survival were 1.5% and 91%, respectively. One patient developed grade 2 RP, and none developed grade 3 RP. No grade 4 toxicities occurred. The unplanned surgical re-intervention rate at 5 years was 33%. No significant changes in echocardiography or cardiac biomarkers after RT were found. CONCLUSION Proton beam RT for breast cancer has low toxicity rates and similar rates of disease control compared with historical data of conventional RT. No early cardiac changes were observed, which paves the way for randomized studies to compare proton beam RT with standard RT.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | | | - Alice Ho
- Massachusetts General Hospital, Boston, MA
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Lin YL. Reirradiation of recurrent breast cancer with proton beam therapy: A case report and literature review. World J Clin Oncol 2019; 10:256-268. [PMID: 31396475 PMCID: PMC6682500 DOI: 10.5306/wjco.v10.i7.256] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2019] [Revised: 06/22/2019] [Accepted: 07/22/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Locoregional recurrence of breast cancer is challenging for clinicians, due to the various former treatments patients have undergone. However, treatment of the recurrence with systemic therapy and subsequent reirradiation of chest wall is accompanied by increased toxicities, particularly radiation-induced cardiovascular disease. Reirradiation by proton beam therapy (PBT) enables superior preservation of adjacent organs at risk as well as concurrent dose escalation for delivery to the gross tumor. This technology is expected to improve the overall outcome of recurrent breast cancer.
CASE SUMMARY A 47-year-old female presented with an extensive locoregional recurrence at 10 yr after primary treatment of a luminal A breast cancer. Because of tumor progression despite having undergone bilateral ovarectomy and systemic therapy, the patient was treated with PBT BE total dose of 64.40 Gy to each gross tumor and 56.00 Gy to the upper mediastinal and retrosternal lymphatics including the entire sternum in 28 fractions. Follow-up computed tomography showed a partial remission, without evidence of newly emerging metastasis. At 19 mo after the PBT, the patient developed a radiation-induced pericardial disease and pleural effusions with clinical burden of dyspnea, which were successfully treated by drainage and corticosteroid. Cytological analysis of the puncture fluid showed no malignancy, and the subsequent computed tomography scan indicated stable disease as well as significantly decreased pericardial and pleural effusions. The patient remains free of progression to date.
CONCLUSION PBT was a safe and effective method of reirradiation for locoregionally recurrent breast cancer in our patient.
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Affiliation(s)
- Yi-Lan Lin
- Department of Radiation Oncology, Rinecker Proton Therapy Center, Munich 81371, Germany
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Smith NL, Jethwa KR, Viehman JK, Harmsen WS, Gonuguntla K, Elswick SM, Grauberger JN, Amundson AC, Whitaker TJ, Remmes NB, Harless CA, Boughey JC, Nguyen MDT, Park SS, Corbin KS, Mutter RW. Post-mastectomy intensity modulated proton therapy after immediate breast reconstruction: Initial report of reconstruction outcomes and predictors of complications. Radiother Oncol 2019; 140:76-83. [PMID: 31185327 DOI: 10.1016/j.radonc.2019.05.022] [Citation(s) in RCA: 36] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2019] [Revised: 05/16/2019] [Accepted: 05/20/2019] [Indexed: 01/02/2023]
Abstract
PURPOSE To report reconstructive outcomes of patients treated with post-mastectomy intensity modulated proton therapy (IMPT) following immediate breast reconstruction (IBR). MATERIALS AND METHODS Consecutive women with breast cancer who underwent implant-based IBR and post-mastectomy IMPT were included. Clinical characteristics, dosimetry, and acute toxicity were collected prospectively and reconstruction complications retrospectively. RESULTS Fifty-one women were treated between 2015 and 2017. Forty-two had bilateral reconstruction with unilateral IMPT. The non-irradiated contralateral breasts served as controls. Conventional fractionation (median 50 Gy/25 fractions) was administered in 37 (73%) and hypofractionation (median 40.5 Gy/15 fractions) in 14 (27%) patients. Median mean heart, ipsilateral lung V20Gy, and CTV-IMN V95% were 0.6 Gy, 13.9%, and 97.4%. Maximal acute dermatitis grade was 1 in 32 (63%), 2 in 17 (33%), and 3 in 2 (4%) patients. Surgical site infection (hazard ratio [HR] 13.19, 95% confidence interval [CI] 1.67-104.03, p = 0.0012), and unplanned surgical intervention (HR 9.86, 95% CI 1.24-78.67, p = 0.0068) were more common in irradiated breasts. Eight of 51 irradiated breasts and 2 of 42 non-irradiated breasts had reconstruction failure (HR 3.59, 95% CI 0.78-16.41, p = 0.084). Among irradiated breasts, hypofractionation was significantly associated with reconstruction failure (HR 4.99, 95% CI 1.24-20.05, p = 0.024), as was older patient age (HR 1.14, 95% CI 1.05-1.24, p = 0.002). CONCLUSIONS IMPT following IBR spared underlying organs and had low rates of acute toxicity. Reconstruction complications are more common in irradiated breasts, and reconstructive outcomes appear comparable with photon literature. Hypofractionation was associated with higher reconstruction failure rates. Further investigation of optimal dose-fractionation after IBR is needed.
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Affiliation(s)
- Na L Smith
- Department of Radiation Oncology, Mayo Clinic, Rochester, USA
| | | | - Jason K Viehman
- Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, USA
| | - William S Harmsen
- Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, USA
| | | | | | | | - Adam C Amundson
- Department of Radiation Oncology, Mayo Clinic, Rochester, USA
| | | | | | | | | | | | - Sean S Park
- Department of Radiation Oncology, Mayo Clinic, Rochester, USA
| | | | - Robert W Mutter
- Department of Radiation Oncology, Mayo Clinic, Rochester, USA.
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Postmastectomy radiotherapy for left-sided breast cancer patients: Comparison of advanced techniques. Med Dosim 2019; 45:34-40. [PMID: 31129035 DOI: 10.1016/j.meddos.2019.04.005] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2019] [Revised: 04/23/2019] [Accepted: 04/30/2019] [Indexed: 12/25/2022]
Abstract
Postmastectomy radiotherapy (PMRT) has been shown to improve the overall survival for invasive breast cancer patients, and many advanced radiotherapy technologies were adopted for PMRT. The purpose of our study is to compare various advanced PMRT techniques including fixed-beam intensity-modulated radiotherapy (IMRT), non-coplanar volumetric modulated arc therapy (NC-VMAT), multiple arc VMAT (MA-VMAT), and tomotherapy (TOMO). Results of standard VMAT and mixed beam therapy that were published by our group previously were also included in the plan comparisons. Treatment plans were produced for nine PMRT patients previously treated in our clinic. The plans were evaluated based on planning target volume (PTV) coverage, dose homogeneity index (DHI), conformity index (CI), dose to organs at risk (OARs), normal tissue complication probability (NTCP) of pneumonitis, lifetime attributable risk (LAR) of second cancers, and risk of coronary events (RCE). All techniques produced clinically acceptable PMRT plans. Overall, fixed-beam IMRT delivered the lowest mean dose to contralateral breast (1.56 ± 0.4 Gy) and exhibited lowest LAR (0.6 ± 0.2%) of secondary contralateral breast cancer; NC-VMAT delivered the lowest mean dose to lungs (7.5 ± 0.8 Gy), exhibited lowest LAR (5.4 ± 2.8%) of secondary lung cancer and lowest NTCP (2.1 ± 0.4%) of pneumonitis; mixed beam therapy delivered the lowest mean dose to heart (7.1 ± 1.3 Gy) and exhibited lowest RCE (8.6 ± 7.1%); TOMO plans provided the most optimal target coverage while delivering higher dose to OARs than other techniques. Both NC-VMAT and MA-VMAT exhibited lower values of all OARs evaluation metrics compare to standard VMAT. Fixed-beam IMRT, NC-VMAT, and mixed beam therapy could be the optimal radiation technique for certain breast cancer patients after mastectomy.
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Remick JS, Bentzen SM, Simone CB, Nichols E, Suntharalingam M, Regine WF. Downstream Effect of a Proton Treatment Center on an Academic Medical Center. Int J Radiat Oncol Biol Phys 2019; 104:756-764. [PMID: 30885776 DOI: 10.1016/j.ijrobp.2019.03.016] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2018] [Revised: 02/22/2019] [Accepted: 03/11/2019] [Indexed: 12/25/2022]
Abstract
PURPOSE To quantify the effects of opening a proton center (PC) on an academic medical center (AMC)/radiation oncology department. METHODS AND MATERIALS Radiation treatment volume and relative value units from fiscal year 2015 (FY15) to FY17 were retrospectively analyzed at the AMC and 2 community-based centers. To quantify new patient referrals to the AMC, we reviewed the electronic medical record for all patients seen at the PC since consults were initiated in November 2015 (n = 1173). Patients were excluded if the date of entry into the AMC electronic medical record predated their PC consultation. Hospital resource use and professional and technical charges were obtained for these patients. Academic growth, philanthropy, and resident education were evaluated based on grant submissions, clinical trial enrollment, philanthropy, and pediatric case exposure, respectively, from PC opening through FY17. RESULTS From FY15 to FY17, radiation fractions at the AMC and the 2 community sites decreased by 14% (95% confidence interval [CI], 12%-16%, P < .001) and increased by 19% (95% CI, 16%-23%, P < .001) and 2% (95% CI, -1.1 to 4.3%, P = NS), respectively; the number of new starts decreased by 3% (95% CI, -13% to 7%, P = NS) and 2% (95% CI, -20% to 16%, P = NS) and increased by 13% (95% CI -2% to 27%, P = NS), respectively. At the AMC, technical and professional relative value units decreased by 5% and 14%, respectively. The PC made 561 external referrals to the AMC, which resulted in $2.38 million technical and $2.13 million professional charges at the AMC. Fifteen grant submissions ($12.83 million) resulted in 6 awards ($3.26 million). Twenty-two clinical trials involving proton therapy were opened, on which a total of 5% (n = 54) of patients enrolled during calendar years 2017 and 2018. The PC was involved in gift donations of $1.6 million. There was a nonsignificant 37% increase in number of pediatric cases. CONCLUSIONS Despite a slight decline in AMC photon patient volumes and relative value units, a positive downstream effect was associated with the addition of a PC, which benefited the AMC.
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Affiliation(s)
- Jill S Remick
- Department of Radiation Oncology, University of Maryland Medical Center, Baltimore, Maryland
| | - Søren M Bentzen
- Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, Maryland
| | - Charles B Simone
- Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, Maryland
| | - Elizabeth Nichols
- Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, Maryland
| | - Mohan Suntharalingam
- Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, Maryland
| | - William F Regine
- Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, Maryland.
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40
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Desai N, Currey A, Kelly T, Bergom C. Nationwide Trends in Heart-Sparing Techniques Utilized in Radiation Therapy for Breast Cancer. Adv Radiat Oncol 2019; 4:246-252. [PMID: 31011669 PMCID: PMC6460327 DOI: 10.1016/j.adro.2019.01.001] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2018] [Accepted: 01/03/2019] [Indexed: 12/14/2022] Open
Abstract
Purpose Radiation dose to the heart correlates with cardiac-related deaths and may partially diminish the benefit of radiation for breast cancer. This study assessed the current nationwide trends in heart-sparing techniques for breast cancer radiation. Methods and Materials In November 2017, an institutional review board–approved survey was sent to radiation oncologists in the United States. Questions assessed demographics and the type and frequency of heart-sparing techniques. Data were analyzed using descriptive statistics and χ2 tests. Results In total, 530 responses (13%) were obtained. Most physicians had practiced >15 years (46%), with most in a private setting (59%). Eighty-three percent of physicians offered prone positioning and/or deep inspiration breath hold (DIBH). This was more common in academic practice (P < .01). Seventy-three percent of physicians used heart-sparing techniques for more than three-fourths of left-sided patients. The most commonly used technique was DIBH, and 43% of physicians used the technique more than three-fourths of the time. Commonly used DIBH systems were Varian RPM (54%) and Vision RT/Align RT (31%). No increase in DIBH use was observed with regional nodal irradiation, and coverage of internal mammary chain nodes varied. Patient tolerance (78%) and cardiac-to-chest wall distance (72%) were the most common determinants of DIBH in left-sided patients. Twenty-three percent of physicians used DIBH for right-sided patients, with lung (64%) and heart sparing (46%) as the most common reasons for use. Lack of facilities was the most common reason not to use DIBH (61%). Conclusions Most respondents offer heart-sparing techniques for breast cancer radiation; this is more common in academic centers. DIBH is the most common technique across all practice settings. DIBH is much less commonly used in right-sided patients but is still used by >20% of practitioners, with lung and heart sparing cited as reasons for use. More data are needed to determine if and when this technique should be used in right-sided cases.
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Affiliation(s)
- Nina Desai
- Medical College of Wisconsin, Department of Radiation Oncology, Milwaukee, Wisconsin
| | - Adam Currey
- Medical College of Wisconsin, Department of Radiation Oncology, Milwaukee, Wisconsin
| | - Tracy Kelly
- Medical College of Wisconsin, Department of Radiation Oncology, Milwaukee, Wisconsin
| | - Carmen Bergom
- Medical College of Wisconsin, Department of Radiation Oncology, Milwaukee, Wisconsin
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Braunstein LZ, Cahlon O. Potential Morbidity Reduction With Proton Radiation Therapy for Breast Cancer. Semin Radiat Oncol 2018; 28:138-149. [PMID: 29735190 DOI: 10.1016/j.semradonc.2017.11.009] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
Proton radiotherapy confers significant dosimetric advantages in the treatment of malignancies that arise adjacent to critical radiosensitive structures. To date, these advantages have been most prominent in the treatment of pediatric and central nervous system malignancies, although emerging data support the use of protons among other anatomical sites in which radiotherapy plays an important role. With advances in the overall treatment paradigm for breast cancer, most patients with localized disease now exhibit long-term disease control and, consequently, may manifest the late toxicities of aggressive treatment. As a result, there is increasing emphasis on the mitigation of iatrogenic morbidity, with particular attention to heart and lung exposure in those receiving adjuvant radiotherapy. Indeed, recent landmark analyses have demonstrated an increase in significant cardiac events that is linked directly to low-dose radiation to the heart. Coupled with practice-changing trials that have expanded the indications for comprehensive regional nodal irradiation, there exists significant interest in employing novel technologies to mitigate cardiac dose while improving target volume coverage. Proton radiotherapy enjoys distinct physical advantages over photon-based approaches and, in appropriately selected patients, markedly improves both target coverage and normal tissue sparing. Here, we review the dosimetric evidence that underlies the putative benefits of proton radiotherapy, and further synthesize early clinical evidence that supports the efficacy and feasibility of proton radiation in breast cancer. Landmark, prospective randomized trials are underway and will ultimately define the role for protons in the treatment of this disease.
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Affiliation(s)
- Lior Z Braunstein
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Oren Cahlon
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY.
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42
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Gee HE, Moses L, Stuart K, Nahar N, Tiver K, Wang T, Ward R, Ahern V. Contouring consensus guidelines in breast cancer radiotherapy: Comparison and systematic review of patterns of failure. J Med Imaging Radiat Oncol 2018; 63:102-115. [PMID: 30267561 DOI: 10.1111/1754-9485.12804] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2018] [Accepted: 08/16/2018] [Indexed: 11/28/2022]
Abstract
Adequate coverage of sites harbouring potential microscopic disease is paramount, where the clinical decision has been made to include regional lymph node radiotherapy for patients with breast cancer. This must be achieved in balance with minimising dose to normal tissues. Several international consensus guidelines detailing clinical target volumes (CTVs) are available, but there is currently no agreement as to which is most appropriate for a given clinical situation. Contouring guidelines are beneficial for routine practice and essential for clinical trial quality assurance. The aims of this study were as follows: to provide a single point of comparison of four commonly used contouring guidelines, including one used in a current Trans-Tasman Radiation Oncology Group trial; and to undertake a systematic review of existing studies which map sites of breast cancer recurrence against contouring guidelines. Two international consensus guidelines (European Society for Radiotherapy and Oncology, and Radiation Therapy Oncology Group) were compared with two clinical trial guidelines (TROG 12.02 PET LABRADOR and the Proton/Photon trial NCT02603341 RADCOMP). Comprehensive literature search for patterns of failure studies was undertaken using Embase and Pubmed. We detail the small but significant differences between the breast consensus guidelines, particularly the supraclavicular (SCF) and internal mammary chain CTVs. Seven series were found mapping recurrence patterns. These results are discussed in the context of the contouring guidelines. Several studies found the SCF CTV is the area at greatest risk of geographical 'miss'. This review will facilitate further discussion about guideline selection and modification, particularly for future clinical trials in Australia and New Zealand.
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Affiliation(s)
- Harriet E Gee
- Crown Princess Mary Cancer Centre, Westmead Hospital, Sydney, New South Wales, Australia.,Sydney Medical School, C24 - Westmead Hospital, The University of Sydney, Sydney, New South Wales, Australia.,Westmead Breast Cancer Institute, Westmead Hospital, Sydney, New South Wales, Australia
| | - Lauren Moses
- Crown Princess Mary Cancer Centre, Westmead Hospital, Sydney, New South Wales, Australia
| | - Kirsty Stuart
- Crown Princess Mary Cancer Centre, Westmead Hospital, Sydney, New South Wales, Australia.,Sydney Medical School, C24 - Westmead Hospital, The University of Sydney, Sydney, New South Wales, Australia.,Westmead Breast Cancer Institute, Westmead Hospital, Sydney, New South Wales, Australia
| | - Najmun Nahar
- Crown Princess Mary Cancer Centre, Westmead Hospital, Sydney, New South Wales, Australia
| | - Ken Tiver
- Crown Princess Mary Cancer Centre, Westmead Hospital, Sydney, New South Wales, Australia.,Nepean Cancer Care Centre, Nepean Hospital, New South Wales, Australia
| | - Tim Wang
- Crown Princess Mary Cancer Centre, Westmead Hospital, Sydney, New South Wales, Australia.,Sydney Medical School, C24 - Westmead Hospital, The University of Sydney, Sydney, New South Wales, Australia.,Westmead Breast Cancer Institute, Westmead Hospital, Sydney, New South Wales, Australia
| | - Rachel Ward
- Crown Princess Mary Cancer Centre, Westmead Hospital, Sydney, New South Wales, Australia
| | - Verity Ahern
- Crown Princess Mary Cancer Centre, Westmead Hospital, Sydney, New South Wales, Australia.,Sydney Medical School, C24 - Westmead Hospital, The University of Sydney, Sydney, New South Wales, Australia.,Westmead Breast Cancer Institute, Westmead Hospital, Sydney, New South Wales, Australia
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Brownlee Z, Garg R, Listo M, Zavitsanos P, Wazer DE, Huber KE. Late complications of radiation therapy for breast cancer: evolution in techniques and risk over time. Gland Surg 2018; 7:371-378. [PMID: 30175054 DOI: 10.21037/gs.2018.01.05] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Radiation therapy in combination with surgery, chemotherapy, and endocrine therapy as indicated, has led to excellent local and distant control of early stage breast cancers. With the majority of these patients surviving long term, mitigating the probability and severity of late toxicities is vital. Radiation to the breast, with or without additional fields for nodal coverage, has the potential to negatively impact long term cosmetic outcome of the treated breast as well as cause rare, but severe, complications due to incidental dosage to the heart, lungs and contralateral breast. The long-term clinical side-effects of breast radiation have been studied extensively. This review aims to discuss the risk of developing late complications following breast radiation and how modern techniques can be used to diminish these risks.
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Affiliation(s)
- Zachary Brownlee
- Department of Radiation Oncology, Tufts Medical Center and Tufts University School of Medicine, Boston, MA, USA
| | - Rashi Garg
- Department of Radiation Oncology, Tufts Medical Center and Tufts University School of Medicine, Boston, MA, USA
| | - Matthew Listo
- Department of Radiation Oncology, Tufts Medical Center and Tufts University School of Medicine, Boston, MA, USA
| | - Peter Zavitsanos
- Department of Radiation Oncology, Tufts Medical Center and Tufts University School of Medicine, Boston, MA, USA
| | - David E Wazer
- Department of Radiation Oncology, Tufts Medical Center and Tufts University School of Medicine, Boston, MA, USA.,Department of Radiation Oncology, Rhode Island Hospital and Brown University School of Medicine, Providence, RI, USA
| | - Kathryn E Huber
- Department of Radiation Oncology, Tufts Medical Center and Tufts University School of Medicine, Boston, MA, USA
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44
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Everett AS, De Los Santos JF, Boggs DH. The Evolving Role of Postmastectomy Radiation Therapy. Surg Clin North Am 2018; 98:801-817. [DOI: 10.1016/j.suc.2018.03.010] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022]
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45
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Impact of dose engine algorithm in pencil beam scanning proton therapy for breast cancer. Phys Med 2018; 50:7-12. [DOI: 10.1016/j.ejmp.2018.05.018] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2018] [Revised: 05/04/2018] [Accepted: 05/17/2018] [Indexed: 11/19/2022] Open
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46
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Zhang R, Heins D, Sanders M, Guo B, Hogstrom K. Evaluation of a mixed beam therapy for postmastectomy breast cancer patients: Bolus electron conformal therapy combined with intensity modulated photon radiotherapy and volumetric modulated photon arc therapy. Med Phys 2018; 45:2912-2924. [PMID: 29749075 DOI: 10.1002/mp.12958] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2017] [Revised: 04/30/2018] [Accepted: 04/30/2018] [Indexed: 12/25/2022] Open
Abstract
PURPOSE The purpose of this study was to assess the potential benefits and limitations of a mixed beam therapy, which combined bolus electron conformal therapy (BECT) with intensity modulated photon radiotherapy (IMRT) and volumetric modulated photon arc therapy (VMAT), for left-sided postmastectomy breast cancer patients. METHODS Mixed beam treatment plans were produced for nine postmastectomy radiotherapy (PMRT) patients previously treated at our clinic with VMAT alone. The mixed beam plans consisted of 40 Gy to the chest wall area using BECT, 40 Gy to the supraclavicular area using parallel opposed IMRT, and 10 Gy to the total planning target volume (PTV) by optimizing VMAT on top of the BECT + IMRT dose distribution. The treatment plans were created in a commercial treatment planning system (TPS), and all plans were evaluated based on PTV coverage, dose homogeneity index (DHI), conformity index (CI), dose to organs at risk (OARs), normal tissue complication probability (NTCP), and secondary cancer complication probability (SCCP). The standard VMAT alone planning technique was used as the reference for comparison. RESULTS Both techniques produced clinically acceptable PMRT plans but with a few significant differences: VMAT showed significantly better CI (0.70 vs 0.53, P < 0.001) and DHI (0.12 vs 0.20, P < 0.001) over mixed beam therapy. For normal tissues, mixed beam therapy showed better OAR sparing and significantly reduced NTCP for cardiac mortality (0.23% vs 0.80%, P = 0.01) and SCCP for contralateral breast (1.7% vs 3.1% based on linear model, and 1.2% vs 1.9% based on linear-exponential model, P < 0.001 in both cases), but showed significantly higher mean (50.8 Gy vs 49.3 Gy, P < 0.001) and maximum skin doses (59.7 Gy vs 53.3 Gy, P < 0.001) compared with VMAT. Patients with more tissue (minimum distance between the distal PTV surface and lung approximately > 0.5 cm and volume of tissue between the distal PTV surface and heart or lung approximately > 250 cm3 ) between distal PTV surface and lung may benefit the most from mixed beam therapy. CONCLUSION This work has demonstrated that mixed beam therapy (BECT + IMRT:VMAT = 4:1) produces clinically acceptable plans having reduced OAR doses and risks of side effects compared with VMAT. Even though VMAT alone produces more homogenous and conformal dose distributions, mixed beam therapy remains as a viable option for treating postmastectomy patients, possibly leading to reduced normal tissue complications.
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Affiliation(s)
- Rui Zhang
- Department of Physics and Astronomy, Louisiana State University, Baton Rouge, LA, 70803, USA.,Department of Radiation Oncology, Mary Bird Perkins Cancer Center, Baton Rouge, LA, 70809, USA
| | - David Heins
- Department of Physics and Astronomy, Louisiana State University, Baton Rouge, LA, 70803, USA
| | - Mary Sanders
- Department of Radiation Oncology, Mary Bird Perkins Cancer Center, Baton Rouge, LA, 70809, USA
| | - Beibei Guo
- Department of Experimental Statistics, Louisiana State University, Baton Rouge, LA, 70803, USA
| | - Kenneth Hogstrom
- Department of Physics and Astronomy, Louisiana State University, Baton Rouge, LA, 70803, USA.,Department of Radiation Oncology, Mary Bird Perkins Cancer Center, Baton Rouge, LA, 70809, USA
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Bergom C, Currey A, Desai N, Tai A, Strauss JB. Deep Inspiration Breath Hold: Techniques and Advantages for Cardiac Sparing During Breast Cancer Irradiation. Front Oncol 2018; 8:87. [PMID: 29670854 PMCID: PMC5893752 DOI: 10.3389/fonc.2018.00087] [Citation(s) in RCA: 117] [Impact Index Per Article: 16.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2018] [Accepted: 03/13/2018] [Indexed: 12/17/2022] Open
Abstract
Historically, heart dose from left-sided breast radiotherapy has been associated with a risk of cardiac injury. Data suggests that there is not a threshold for the deleterious effects from radiation on the heart. Over the past several years, advances in radiation delivery techniques have reduced cardiac morbidity due to treatment. Deep inspiration breath hold (DIBH) is a technique that takes advantage of a more favorable position of the heart during inspiration to minimize heart doses over a course of radiation therapy. In the accompanying review article, we outline several methods used to deliver treatment with DIBH, quantify the benefits of DIBH treatment, discuss considerations for patient selection, and identify challenges associated with DIBH techniques.
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Affiliation(s)
- Carmen Bergom
- Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI, United States
| | - Adam Currey
- Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI, United States
| | - Nina Desai
- Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI, United States
| | - An Tai
- Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI, United States
| | - Jonathan B Strauss
- Department of Radiation Oncology, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States
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48
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Electron postmastectomy chest wall plus comprehensive nodal irradiation technique using Electron Monte Carlo dose algorithm. Med Dosim 2018; 43:230-236. [DOI: 10.1016/j.meddos.2017.08.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2017] [Revised: 08/25/2017] [Accepted: 08/28/2017] [Indexed: 11/22/2022]
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49
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Internal mammary lymph nodes radiotherapy of breast cancer in the era of individualized medicine. Oncotarget 2017; 8:81583-81590. [PMID: 29113416 PMCID: PMC5655311 DOI: 10.18632/oncotarget.20186] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2017] [Accepted: 07/25/2017] [Indexed: 12/26/2022] Open
Abstract
Inclusion internal mammary lymph nodes as a part of regional nodal irradiation have a potential to reduce local recurrence, distant recurrence, and improve survival in breast cancer. However, the increased risk of cardiac toxicity and lungs injure associated with internal mammary lymph nodes irradiation has drew more and more attention. Estimating risk of metastasis in internal mammary lymph nodes based on axillary lymph nodes metastasis status is not always reliable: low-risk do not always mean negative in internal mammary lymph nodes and high-risk do not always indicate positive in internal mammary lymph nodes. Inaccurate prediction of in internal mammary lymph nodes metastasis might lead to over- or under-treatment of in internal mammary lymph node. Internal mammary sentinel lymph node biopsy is a minimally invasive technique which has a high potential to accurately evaluate the metastasis status in in internal mammary lymph nodes and improve accuracy of nodal staging. This technique might be a useful tool to guide individualized internal mammary lymph nodes irradiation.
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50
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The impact of active breathing control on internal mammary lymph node coverage and normal tissue exposure in breast cancer patients planned for left-sided postmastectomy radiation therapy. Pract Radiat Oncol 2017; 7:228-233. [DOI: 10.1016/j.prro.2016.11.010] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2016] [Revised: 11/27/2016] [Accepted: 11/30/2016] [Indexed: 12/25/2022]
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