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Unterkirhere O, Streller T, Jeller D, Logaritsch P, Bucher S, Dubsky P, Glanzmann C, Studer G. Tolerance of Adjuvant Ultrahypofractionated Whole-Breast Radiation Therapy Employing Moderately Hypofractionated Sequential Boost: A Single Institution Analysis. Adv Radiat Oncol 2025; 10:101756. [PMID: 40236460 PMCID: PMC11999331 DOI: 10.1016/j.adro.2025.101756] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2024] [Accepted: 02/28/2025] [Indexed: 04/17/2025] Open
Abstract
Purpose This analysis evaluates early and intermediate treatment tolerance in a prospective observational cohort study of patients who underwent adjuvant ultrahypofractionated whole-breast radiation therapy (uhWBRT), with or without moderately hypofractionated sequential boost, following breast-conserving surgery. Methods and Materials uhWBRT was introduced in our department in March 2020. Data from 436 patients with breast tumors not requiring lymphatic irradiation were analyzed, including 376 with invasive carcinomas (pT1-pT3) and 60 with ductal carcinoma in situ. The mean age was 62 years (range, 26-85). Acute reactions (Common Terminology Criteria for Adverse Events v4.03) were assessed at radiation therapy completion and after 2 to 3 weeks. Late effects and patient-reported outcomes (Late Effects in Normal Tissues-Subjective, Objective, Management and Analytic and Harvard for Cosmesis) were evaluated at 6 months after radiation therapy and annually thereafter. The prescribed uhWBRT dose was 26 Gy in 5 daily fractions. A sequential boost of 10.0 to 12.5 Gy in 4 to 5 daily fractions was administered to 338 patients (77.5%), while 98 (22.5%) did not receive a boost. Results Acute toxicity grades 0, 1, and 2 were observed in 29.8%, 59.9%, and 10.3% of patients, respectively, at radiation therapy completion and 52.1%, 40.8%, and 7.2% of patients at 2 to 3 weeks after radiation therapy. Grade 2 late effects were identified in 5.3%, 2.0%, 1.8%, 1.1%, and 0%, and grade 3 late effects were identified in 1.5%, 2.3%, 0.9%, 0%, and 0% of patients at 6 months, 1 years, 2 years, 3 years, and 4 years. Patient-reported outcomes for cosmesis were rated as good or excellent in 97.7% of patients. After a mean follow-up of 18 months (median 14, range, 0-48), 1 local failure, 2 nodal failures, and 9 distant relapses were detected. Three deaths were reported, all nontumor-related. Conclusions Early and intermediate results indicate that the treatment schedules, including the moderately hypofractionated boost, are safe and well tolerated, with acute toxicity rates comparable to those in the FAST-Forward trial. Although our study follow up is relatively short, our findings indicate that uhWBRT, with or without a moderately hypofractionated boost, is safe and well tolerated.
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Affiliation(s)
- Olga Unterkirhere
- Radiation Oncology Department, Kantonsspital Luzern, Luzern, Switzerland
| | - Tino Streller
- Radiation Oncology Department, Kantonsspital Luzern, Luzern, Switzerland
| | - David Jeller
- Radiation Oncology Department, Kantonsspital Luzern, Luzern, Switzerland
| | | | - Susanne Bucher
- Breast Center, Kantonsspital Luzern, Luzern, Switzerland
| | - Peter Dubsky
- University of Lucerne, Luzern, Switzerland
- Tumour- and Breast Cancer Centre at the Hirslanden Klinik St. Anna, Lucerne, Switzerland
| | | | - Gabriela Studer
- Radiation Oncology Department, Kantonsspital Luzern, Luzern, Switzerland
- University of Lucerne, Luzern, Switzerland
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Tauber N, Amann N, Dannehl D, Deutsch TM, Dimpfl M, Fasching P, Hartkopf A, Heublein S, Hilmer L, Hörner M, Krawczyk N, Krückel A, Krug D, Marmé F, Michel LL, Reinisch M, Rody A, Schäffler H, Schneeweiss A, Utz D, Veselinovic K, Banys-Paluchowski M. Therapy of early breast cancer: current status and perspectives. Arch Gynecol Obstet 2025:10.1007/s00404-025-08028-0. [PMID: 40261372 DOI: 10.1007/s00404-025-08028-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2025] [Accepted: 04/01/2025] [Indexed: 04/24/2025]
Abstract
Medical advancements in breast cancer are truly remarkable. Especially in recent years, numerous new therapeutics have been approved and surgical strategies have been de-escalated for specific patient groups. In the therapeutic setting, CDK4/6 inhibitors as oral maintenance therapy in early breast cancer and immune checkpoint inhibitors (Pembrolizumab) for triple-negative breast cancer (BC) are noteworthy. In the surgical field, prospective randomized controlled trials have currently explored the possibility to deescalate axillary surgery by omitting sentinel lymph node excision (INSEMA, SOUND). As a result, there have been significant improvements in prognosis and a reduction in surgical morbidity for patients. Many exciting trials are underway, and it remains to be seen whether antibody-drug conjugates beyond trastuzumab emtansine, will find their way into the treatment lines for early-stage BC. Furthermore, the integration of artificial intelligence in both diagnostics and treatment recommendation evaluation is a promising area with great potential.
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Affiliation(s)
- Nikolas Tauber
- Department of Obstetrics and Gynecology, University Hospital Schleswig-Holstein, Campus Luebeck, Luebeck, Germany.
| | - Niklas Amann
- Department of Obstetrics and Gynecology, Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN), Erlangen University Hospital, Friedrich Alexander University of Erlangen-Nuremberg (FAU), Erlangen, Germany
| | - Dominik Dannehl
- Department of Obstetrics and Gynecology, University Hospital Tuebingen, 72016, Tuebingen, Germany
| | - Thomas M Deutsch
- Department of Obstetrics and Gynecology, University Hospital Heidelberg, Heidelberg, Germany
| | - Moritz Dimpfl
- Department of Obstetrics and Gynecology, Medical Faculty Mannheim, University Medical Center Mannheim, University of Heidelberg, Mannheim, Deutschland
| | - Peter Fasching
- Department of Obstetrics and Gynecology, Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN), Erlangen University Hospital, Friedrich Alexander University of Erlangen-Nuremberg (FAU), Erlangen, Germany
| | - Andreas Hartkopf
- Department of Obstetrics and Gynecology, University Hospital Tuebingen, 72016, Tuebingen, Germany
| | - Sabine Heublein
- Department of Obstetrics and Gynecology, University Hospital Ulm, 89075, Ulm, Germany
| | - Lisbeth Hilmer
- Department of Obstetrics and Gynecology, University Hospital Schleswig-Holstein, Campus Luebeck, Luebeck, Germany
| | - Manuel Hörner
- Department of Obstetrics and Gynecology, Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN), Erlangen University Hospital, Friedrich Alexander University of Erlangen-Nuremberg (FAU), Erlangen, Germany
| | - Natalia Krawczyk
- Department of Obstetrics and Gynecology, University Hospital Duesseldorf, 40225, Duesseldorf, Germany
| | - Annika Krückel
- Department of Obstetrics and Gynecology, Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN), Erlangen University Hospital, Friedrich Alexander University of Erlangen-Nuremberg (FAU), Erlangen, Germany
| | - David Krug
- Department of Radiotherapy and Radiation Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Frederik Marmé
- Department of Obstetrics and Gynecology, Medical Faculty Mannheim, University Medical Center Mannheim, University of Heidelberg, Mannheim, Deutschland
| | - Laura L Michel
- National Center for Tumor Diseases, University Hospital and German Cancer Research Center Heidelberg, 69120, Heidelberg, Germany
| | - Mattea Reinisch
- Department of Obstetrics and Gynecology, Medical Faculty Mannheim, University Medical Center Mannheim, University of Heidelberg, Mannheim, Deutschland
| | - Achim Rody
- Department of Obstetrics and Gynecology, University Hospital Schleswig-Holstein, Campus Luebeck, Luebeck, Germany
| | - Henning Schäffler
- Department of Obstetrics and Gynecology, University Hospital Ulm, 89075, Ulm, Germany
| | - Andreas Schneeweiss
- National Center for Tumor Diseases, University Hospital and German Cancer Research Center Heidelberg, 69120, Heidelberg, Germany
- German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany
| | - David Utz
- Department of Internal Medicine VIII, Medical Oncology and Pneumology, University Hospital Tuebingen, 72016, Tuebingen, Germany
| | - Kristina Veselinovic
- Department of Obstetrics and Gynecology, University Hospital Ulm, 89075, Ulm, Germany
| | - Maggie Banys-Paluchowski
- Department of Obstetrics and Gynecology, University Hospital Schleswig-Holstein, Campus Luebeck, Luebeck, Germany
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Saadatmand P, Esmailzadeh A, Mahdavi SR, Nikoofar A, Jazaeri SZ, Esmaili G, Vejdani S. Prediction of acute skin toxicity in tomotherapy of breast cancer using skin DVH data. Sci Rep 2025; 15:11208. [PMID: 40175430 PMCID: PMC11965445 DOI: 10.1038/s41598-025-95185-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2024] [Accepted: 03/19/2025] [Indexed: 04/04/2025] Open
Abstract
Investigation and quantification of the relationship between the skin dose-volume histogram (DVH) and the risk of acute skin toxicity in breast cancer patients undergoing Tomotherapy by regression modeling. This prospective study included 52 breast cancer patients treated with Tomotherapy in the dose range of 42.5-60 Gy to the planned target volume. Grading of acute skin toxicity in patients was assessed by the maximum score recorded in weekly follow-ups during and up to three months' post-radiation therapy using the Common Terminology Criteria for Adverse Events (CTCAE) v4.0 guidelines. A superficial layer with a thickness of 2 mm was designated as the Skin Representative Layer (SRL-2) on the Tomotherapy planning, and DVH was extracted for that. Then, multivariable and univariable logistic analyses were performed to identify the most predictive variables of acute skin toxicity from SRL-2 DVH values and patients' clinical parameters. The regression analysis identified V51Gy, representing the absolute SRL-2 volume receiving 51 Gy or more in physical dose, as the most predictive dosimetric parameter for grade 2-3 acute skin toxicity. The optimal cut-off value was 4.74 cc for the physical dose, with an Area Under the Receiver Operating Characteristic (ROC) Curve (AUC) value of 0.749, even when adjusted for clinical and treatment-related variables. The logistic model based on V51Gy demonstrated superior calibration, with a slope and R² value approaching 1, indicating better agreement between predicted and observed outcomes. The risk of acute skin toxicity during breast cancer Tomotherapy is correlated with the V51Gy parameter of skin DVH. Limiting V51Gy < 4.74 cc, or 23.7 cm2 of skin area, should keep the risk of grade 2-3 acute skin toxicity below 26%.
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Affiliation(s)
- Pegah Saadatmand
- Department of Medical Physics, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Arman Esmailzadeh
- Department of Medical Physics, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
- Department of Medical Physics, Iran University of Medical Sciences, Hemmat Highway, Tehran, Iran.
| | - Seied Rabi Mahdavi
- Department of Medical Physics, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
- Radiation Biology Research Center, Iran University of Medical Sciences, Tehran, Iran.
- Department of Medical Physics, Iran University of Medical Sciences, Hemmat Highway, Tehran, Iran.
| | - Alireza Nikoofar
- Department of Radiation Oncology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Seyede Zohreh Jazaeri
- Department of Neuroscience, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran
- Division of Neuroscience, Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran
| | | | - Soheil Vejdani
- Department of Radiation Oncology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
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Piroth MD, Krug D, Baumann R, Strnad V, Borm K, Combs S, Corradini S, Duma MN, Dunst J, Fastner G, Feyer P, Fietkau R, Harms W, Hehr T, Hörner-Rieber J, Matuschek C, Schmeel C, Budach W. Implant-based reconstruction and adjuvant radiotherapy in breast cancer patients-current status and DEGRO recommendations. Strahlenther Onkol 2025; 201:353-367. [PMID: 39786586 PMCID: PMC11928413 DOI: 10.1007/s00066-024-02334-3] [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: 11/01/2024] [Accepted: 11/10/2024] [Indexed: 01/12/2025]
Abstract
PURPOSE The aim of this review is to give an overview of the results of prospective and retrospective studies using allogenic reconstruction and postmastectomy radiotherapy (PMRT) in breast cancer and to make recommendations regarding this interdisciplinary approach. MATERIALS AND METHODS A PubMed search was conducted to extract relevant articles from 2000 to 2024. The search was performed using the following terms: (breast cancer) AND (reconstruction OR implant OR expander) AND (radiotherapy OR radiation). Data from the literature on allogenic breast reconstruction and radiation are presented and discussed in relation to toxicity and cosmesis. CONCLUSION AND RECOMMENDATIONS Breast reconstruction is also feasible if PMRT is necessary. Patients need to be informed about the relevant risk of capsular fibrosis and implant failure. A planned reconstruction is no reason to forgo PMRT nor is an indication for PMRT a reason to forego implant-based breast reconstruction if desired by the patient. It is important to provide detailed information here to enable shared decision-making. There is still no clear consensus regarding implant-based reconstruction (IBR) and PMRT. However, in clinical practice, both a one-stage (immediate "implant-direct" IBR) procedure with PMRT up to the final implant and a two-stage (immediate-delayed IBR) procedure with PMRT up to the tissue expander (TE) and later exchange of the TE are used; both approaches have their specific advantages and disadvantages. Depending on patient-specific factors and the surgeon's experience and estimates, both IBR procedures are also possible in combination with PMRT. When using a TE/implant approach, completing skin stretching by adequately filling the expander before PMRT may be favorable. This approach is particularly practical when adjuvant chemotherapy is planned but may lead to postponement of radiotherapy when primary systemic therapy is given. According to the latest data, moderate hypofractionation also appears to be safe in the context of the IBR approach. It is important to have a closely coordinated interdisciplinary approach and to fully inform patients about the increased rate of potential side effects.
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Affiliation(s)
- M D Piroth
- Department of Radiation Oncology, HELIOS University Hospital Wuppertal, Witten/Herdecke University, Heusnerstraße 40, 42283, Wuppertal, Germany.
| | - D Krug
- Department of Radiotherapy and Radiation Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - R Baumann
- Department of Radiation Oncology, St. Marien-Krankenhaus, Siegen, Germany
| | - V Strnad
- Department of Radiation Oncology, University Hospital Erlangen, Erlangen, Germany
| | - K Borm
- TUM School of Medicine, Department of Radiation Oncology, Technical University of Munich, Munich, Germany
| | - S Combs
- TUM School of Medicine, Department of Radiation Oncology, Technical University of Munich, Munich, Germany
- Partner Site Munich, Deutsches Konsortium für Translationale Krebsforschung (DKTK), Munich, Germany
- Department of Radiation Medicine (IRM), Helmholtz Zentrum München (HMGU), Neuherberg, Germany
| | - S Corradini
- Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany
| | - M N Duma
- Department of Radiation Oncology, Helios Clinics of Schwerin-University Campus of MSH Medical School Hamburg, Schwerin, Germany
- Department for Human Medicine, MSH Medical School Hamburg, Hamburg, Germany
| | - J Dunst
- Department of Radiation Oncology, University Hospital Schleswig-Holstein, Kiel, Germany
| | - G Fastner
- Department of Radiotherapy and Radio-Oncology, University Hospital Salzburg, Landeskrankenhaus, Paracelsus Medical University, Salzburg, Austria
| | - P Feyer
- Formerly Department of Radiation Oncology, Vivantes Hospital Neukölln, Berlin, Germany
| | - R Fietkau
- Department of Radiation Oncology, University Hospital Erlangen, Erlangen, Germany
| | - W Harms
- Department of Radiation Oncology, St. Claraspital, Basel, Switzerland
| | - T Hehr
- Department of Radiation Oncology, Marienhospital Stuttgart, Stuttgart, Germany
| | - J Hörner-Rieber
- Department of Radiation Oncology, University Hospital Düsseldorf, Düsseldorf, Germany
| | - C Matuschek
- Department of Radiotherapy and Radiation Oncology, Bielefeld University, Medical School and University Medical Center OWL, Campus Klinikum Mitte, Bielefeld, Germany
| | - C Schmeel
- Department of Radiation Oncology, University Hospital Bonn, Bonn, Germany
| | - W Budach
- Department of Radiation Oncology, University Hospital Düsseldorf, Düsseldorf, Germany
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Rodin D, Glicksman RM, Hepel JT, Huber K, Kirova Y, Loap P, Rakovitch E. Early-Stage Breast Cancer: A Critical Review of Current and Emerging Practice. Int J Radiat Oncol Biol Phys 2024; 120:1260-1272. [PMID: 39237044 DOI: 10.1016/j.ijrobp.2024.08.037] [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: 06/20/2024] [Revised: 08/05/2024] [Accepted: 08/09/2024] [Indexed: 09/07/2024]
Abstract
Breast-conserving surgery followed by adjuvant radiation to reduce the risk of ipsilateral breast tumor recurrence is the mainstay of treatment for early-stage breast cancer (ESBC). However, improved understanding of the heterogeneity of the clinical and molecular characteristics of ESBC has led to greater efforts to personalize approaches to treatment. Furthermore, advances in the understanding of the radiobiology of breast cancer have led to several practice-changing trials on the effectiveness and tolerability of moderate and ultrahypofractionated radiation. Here, we review the recent evidence and ongoing research in the radiotherapeutic management of ESBC, including the use of boost for high-risk disease and opportunities for accelerated fractionation, partial breast irradiation, and radiation omission for low-risk disease. We also discuss how molecular profiling can inform decision-making and new opportunities for primary radiation therapy and reirradiation.
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Affiliation(s)
- Danielle Rodin
- Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Department of Radiation Oncology, University of Toronto, Ontario, Canada.
| | - Rachel M Glicksman
- Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Ontario, Canada
| | - Jaroslaw T Hepel
- Department of Radiation Oncology, Rhode Island Hospital, Providence, Rhode Island
| | - Kathryn Huber
- Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Tufts University, Boston, Massachusetts
| | - Youlia Kirova
- Department of Radiation Oncology, Institut Curie, Paris, France
| | - Pierre Loap
- Department of Radiation Oncology, Institut Curie, Paris, France
| | - Eileen Rakovitch
- Department of Radiation Oncology, University of Toronto, Ontario, Canada; Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
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Lee SF, Kennedy SKF, Caini S, Wong HCY, Yip PL, Poortmans PM, Meattini I, Kaidar-Person O, Recht A, Hijal T, Torres MA, Cao JQ, Corbin KS, Choi JI, Koh WY, Kwan JYY, Karam I, Chan AW, Chow E, Marta GN. Randomised controlled trials on radiation dose fractionation in breast cancer: systematic review and meta-analysis with emphasis on side effects and cosmesis. BMJ 2024; 386:e079089. [PMID: 39260879 PMCID: PMC11388113 DOI: 10.1136/bmj-2023-079089] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 07/25/2024] [Indexed: 09/13/2024]
Abstract
OBJECTIVE To provide a comprehensive assessment of various fractionation schemes in radiation therapy for breast cancer, with a focus on side effects, cosmesis, quality of life, risks of recurrence, and survival outcomes. DESIGN Systematic review and meta-analysis. DATA SOURCES Ovid MEDLINE, Embase, and Cochrane Central Register of Controlled Trials (from inception to 23 October 2023). STUDY SELECTION Included studies were randomised controlled trials focusing on conventional fractionation (CF; daily fractions of 1.8-2 Gy, reaching a total dose of 50-50.4 Gy over 5-6 weeks), moderate hypofractionation (MHF; fraction sizes of 2.65-3.3 Gy for 13-16 fractions over 3-5 weeks), and/or ultra-hypofractionation (UHF; schedule of only 5 fractions). DATA EXTRACTION Two independent investigators screened studies and extracted data. Risk of bias and quality of evidence were assessed using the Cochrane Collaboration's tool and the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) approach, respectively. DATA SYNTHESIS Pooled risk ratios (RRs) and hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using a random effects model. Heterogeneity was analysed using Cochran's Q test and I2 statistic. Network meta-analysis was used to integrate all available evidence. MAIN OUTCOME MEASURES The pre-specified primary outcome was grade ≥2 acute radiation dermatitis and late radiation therapy related side effects; secondary outcomes included cosmesis, quality of life, recurrence, and survival metrics. RESULTS From 1754 studies, 59 articles representing 35 trials (20 237 patients) were assessed; 21.6% of outcomes showed low risk of bias, whereas 78.4% had some concerns or high risk, particularly in outcome measurement (47.4%). The RR for grade ≥2 acute radiation dermatitis for MHF compared with CF was 0.54 (95% CI 0.49 to 0.61; P<0.001) and 0.68 (0.49 to 0.93; P=0.02) following breast conserving therapy and mastectomy, respectively. Hyperpigmentation and grade ≥2 breast shrinkage were less frequent after MHF than after CF, with RRs of 0.77 (0.62 to 0.95; P=0.02) and 0.92 (0.85 to 0.99; P=0.03), respectively, in the combined breast conserving therapy and mastectomy population. However, in the breast conserving therapy only trials, these differences in hyperpigmentation (RR 0.79, 0.60 to 1.03; P=0.08) and breast shrinkage (0.94, 0.83 to 1.07; P=0.35) were not statistically significant. The RR for grade ≥2 acute radiation dermatitis for UHF compared with MHF was 0.85 (0.47 to 1.55; P=0.60) for breast conserving therapy and mastectomy patients combined. MHF was associated with improved cosmesis and quality of life compared with CF, whereas data on UHF were less conclusive. Survival and recurrence outcomes were similar between UHF, MHF, and CF. CONCLUSIONS MHF shows improved safety profile, cosmesis, and quality of life compared with CF while maintaining equivalent oncological outcomes. Fewer randomised controlled trials have compared UHF with other fractionation schedules, but its safety and oncological effectiveness seem to be similar with short term follow-up. Given the advantages of reduced treatment time, enhanced convenience for patients, and potential cost effectiveness, MHF and UHF should be considered as preferred options over CF in appropriate clinical settings, with further research needed to solidify these findings. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42023460249.
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Affiliation(s)
- Shing Fung Lee
- Department of Radiation Oncology, National University Cancer Institute, National University Hospital, Singapore
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Samantha K F Kennedy
- Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada
| | - Saverio Caini
- Cancer Risk Factors and Lifestyle Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network (ISPO), Florence, Italy
| | - Henry C Y Wong
- Department of Oncology, Princess Margaret Hospital, Hospital Authority, Hong Kong
| | - Pui Lam Yip
- Department of Radiation Oncology, National University Cancer Institute, National University Hospital, Singapore
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
- Department of Clinical Oncology, Tuen Mun Hospital, New Territories West Cluster, Hospital Authority, Hong Kong
| | - Philip M Poortmans
- Department of Radiation Oncology, Iridium Netwerk, Wilrijk-Antwerp, Belgium
- Faculty of Medicine and Health Sciences, University of Antwerp, Wilrijk-Antwerp, Belgium
| | - Icro Meattini
- Department of Experimental and Clinical Biomedical Sciences "M Serio", University of Florence, Florence, Italy
- Radiation Oncology Unit, Oncology Department, Azienda Ospedaliero Universitaria Careggi, Florence, Italy
| | - Orit Kaidar-Person
- Breast Cancer Radiation Therapy Unit, Sheba Medical Center, Ramat Gan, Israel
- School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
- GROW-School for Oncology and Reproductive (Maastro), Maastricht University, Maastricht, Netherlands
| | - Abram Recht
- Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Tarek Hijal
- Division of Radiation Oncology, McGill University Health Centre, Montreal, QC, Canada
| | - Mylin A Torres
- Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA
| | - Jeffrey Q Cao
- Section of Radiation Oncology, Department of Oncology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
| | | | - J Isabelle Choi
- Department of Radiation Oncology, New York Proton Center and Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Wee Yao Koh
- Department of Radiation Oncology, National University Cancer Institute, National University Hospital, Singapore
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Jennifer Y Y Kwan
- Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
- Department of Radiation Oncology, University of Toronto, Toronto, ON, Canada
| | - Irene Karam
- Department of Radiation Oncology, University of Toronto, Toronto, ON, Canada
- Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada
| | - Adrian W Chan
- Department of Radiation Oncology, University of Toronto, Toronto, ON, Canada
- Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada
| | - Edward Chow
- Department of Radiation Oncology, University of Toronto, Toronto, ON, Canada
- Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada
| | - Gustavo N Marta
- Department of Radiation Oncology, Hospital Sírio-Libanês, São Paulo, Brazil
- Latin America Cooperative Oncology Group, Porto Alegre, Brazil
- Postgraduate Program, Department of Radiology and Oncology, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
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7
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Gruber G. Escalation and De-Escalation of Adjuvant Radiotherapy in Early Breast Cancer: Strategies for Risk-Adapted Optimization. Cancers (Basel) 2024; 16:2946. [PMID: 39272804 PMCID: PMC11394564 DOI: 10.3390/cancers16172946] [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: 07/01/2024] [Revised: 08/12/2024] [Accepted: 08/20/2024] [Indexed: 09/15/2024] Open
Abstract
Postoperative radiotherapy (RT) is recommended after breast-conserving surgery and mastectomy (with risk factors). Consideration of pros and cons, including potential side effects, demands the optimization of adjuvant RT and a risk-adapted approach. There is clear de-escalation in fractionation-hypofractionation should be considered standard. For selected low-risk situations, PBI only or even the omission of RT might be appropriate. In contrast, tendencies toward escalating RT are obvious. Preoperative RT seems attractive for patients in whom breast reconstruction is planned or for defining the tumor location more precisely with the potential of giving ablative doses. Dose escalation by a (simultaneous integrated) boost or the combination with new compounds/systemic treatments may increase antitumor efficacy but also toxicity. Despite low evidence, RT for oligometastatic disease is becoming increasingly popular. The omission of axillary dissection in node-positive disease led to an escalation of regional RT. Studies are ongoing to test if any axillary treatment can be omitted and which oligometastatic patients do really benefit from RT. Besides technical improvements, the incorporation of molecular risk profiles and also the response to neoadjuvant systemic therapy have the potential to optimize the decision-making concerning if and how local and/or regional RT should be administered.
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Affiliation(s)
- Guenther Gruber
- Institute for Radiotherapy, Klinik Hirslanden, Witellikerstrasse 40, CH-8032 Zurich, Switzerland
- Medical School, University of Nicosia, CY-1700 Nicosia, Cyprus
- Medical Faculty, University of Berne, CH-3000 Berne, Switzerland
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8
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Ji MC, Li ZJ, Li K, Wang YX, Yang B, Lv LL, Su Y, Zhang ZW, Huo ZC, Qi Q, Lu YC, Cui ZQ, Liu YB. Dosimetric risk factors for radiation esophagitis in patients with breast cancer following regional nodal radiation. World J Clin Cases 2024; 12:2995-3003. [PMID: 38898857 PMCID: PMC11185373 DOI: 10.12998/wjcc.v12.i17.2995] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2024] [Revised: 03/25/2024] [Accepted: 04/22/2024] [Indexed: 06/04/2024] Open
Abstract
BACKGROUND Radiation esophagitis (RE) is one of the most common clinical symptoms of regi-onal lymph node radiotherapy for breast cancer. However, there are fewer studies focusing on RE caused by hypofractionated radiotherapy (HFRT). AIM To analyze the clinical and dosimetric factors that contribute to the development of RE in patients with breast cancer treated with HFRT of regional lymph nodes. METHODS Between January and December 2022, we retrospectively analysed 64 patients with breast cancer who met our inclusion criteria underwent regional nodal intensity-modulated radiotherapy at a radiotherapy dose of 43.5 Gy/15F. RESULTS Of the 64 patients in this study, 24 (37.5%) did not develop RE, 29 (45.3%) developed grade 1 RE (G1RE), 11 (17.2%) developed grade 2 RE (G2RE), and none developed grade 3 RE or higher. Our univariable logistic regression analysis found G2RE to be significantly correlated with the maximum dose, mean dose, relative volume 20-40, and absolute volume (AV) 20-40. Our stepwise linear regression analyses found AV30 and AV35 to be significantly associated with G2RE (P < 0.001). The optimal threshold for AV30 was 2.39 mL [area under the curve (AUC): 0.996; sensitivity: 90.9%; specificity: 91.1%]. The optimal threshold for AV35 was 0.71 mL (AUC: 0.932; sensitivity: 90.9%; specificity: 83.9%). CONCLUSION AV30 and AV35 were significantly associated with G2RE. The thresholds for AV30 and AV35 should be limited to 2.39 mL and 0.71 mL, respectively.
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Affiliation(s)
- Mei-Chen Ji
- Oncology Center, The Affiliated Hospital of Hebei University of En-gineering, Handan 056002, Hebei Province, China
| | - Zhi-Jia Li
- Oncology Center, The Affiliated Hospital of Hebei University of En-gineering, Handan 056002, Hebei Province, China
| | - Ke Li
- Oncology Center, The Affiliated Hospital of Hebei University of En-gineering, Handan 056002, Hebei Province, China
| | - Yun-Xiao Wang
- Oncology Center, The Affiliated Hospital of Hebei University of En-gineering, Handan 056002, Hebei Province, China
| | - Bo Yang
- Oncology Center, The Affiliated Hospital of Hebei University of En-gineering, Handan 056002, Hebei Province, China
| | - Lin-Lin Lv
- Oncology Center, The Affiliated Hospital of Hebei University of En-gineering, Handan 056002, Hebei Province, China
| | - Ying Su
- Oncology Center, The Affiliated Hospital of Hebei University of En-gineering, Handan 056002, Hebei Province, China
| | - Zhi-Wei Zhang
- Oncology Center, The Affiliated Hospital of Hebei University of En-gineering, Handan 056002, Hebei Province, China
| | - Zhong-Chao Huo
- Oncology Center, The Affiliated Hospital of Hebei University of En-gineering, Handan 056002, Hebei Province, China
| | - Qing Qi
- Oncology Center, The Affiliated Hospital of Hebei University of En-gineering, Handan 056002, Hebei Province, China
| | - Yong-Chang Lu
- General Surgery Department, Handan First Hospital, Handan 056002, Hebei Province, China
| | - Zhi-Qiang Cui
- Department of Breast Surgery, The Affiliated Hospital of Hebei University of Engineering, Handan 056002, Hebei Province, China
| | - Yan-Bao Liu
- School of Clinical Medicine, Hebei University of Engineering, Handan 056002, Hebei Province, China
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9
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Krug D, Banys-Paluchowski M, Brucker SY, Denkert C, Ditsch N, Fasching PA, Haidinger R, Harbeck N, Heil J, Huober J, Jackisch C, Janni W, Kolberg HC, Loibl S, Lüftner D, van Mackelenbergh M, Radosa JC, Reimer T, Welslau M, Würstlein R, Untch M, Budach W. Radiotherapy statements of the 18th St. Gallen International Breast Cancer Consensus Conference-a German expert perspective. Strahlenther Onkol 2024; 200:461-467. [PMID: 38393398 PMCID: PMC11111516 DOI: 10.1007/s00066-024-02209-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2023] [Accepted: 01/23/2024] [Indexed: 02/25/2024]
Abstract
PURPOSE To summarize the radiotherapy-relevant statements of the 18th St. Gallen Breast Cancer Consensus Conference and interpret the findings in light of German guideline recommendations. METHODS Statements and voting results from the 18th St. Gallen International Breast Cancer Consensus Conference were collected and analyzed according to their relevance for the radiation oncology community. The voting results were discussed in two hybrid meetings among the authors of this manuscript on March 18 and 19, 2023, in light of the German S3 guideline and the 2023 version of the Arbeitsgemeinschaft Gynäkologische Onkologie (AGO) guidelines. RESULTS AND CONCLUSION There was a high level of agreement between the radiotherapy-related statements of the 18th St. Gallen International Breast Cancer Consensus Conference and the German S3 and AGO guidelines. Discrepancies include the impact of number of lymph node metastases for the indication for postmastectomy radiotherapy.
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Affiliation(s)
- David Krug
- Klinik für Strahlentherapie, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Arnold-Heller-Straße 3, Haus L, 24105, Kiel, Germany.
| | - Maggie Banys-Paluchowski
- Klinik für Frauenheilkunde und Geburtshilfe, Brustzentrum, Campus Lübeck, Universitätsklinikum Schleswig-Holstein, Lübeck, Germany
| | | | - Carsten Denkert
- Institut für Pathologie, Philipps-Universität Marburg und Universitätsklinikum Marburg (UKGM), Marburg, Germany
| | - Nina Ditsch
- Klinik für Frauenheilkunde und Geburtshilfe, Brustzentrum, Universitätsklinikum Augsburg, Augsburg, Germany
| | - Peter A Fasching
- Frauenklinik des Universitätsklinikums Erlangen, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
| | | | - Nadia Harbeck
- Brustzentrum, Frauenklinik, LMU Klinikum München, Munich, Germany
| | - Jörg Heil
- Brustzentrum Heidelberg, Klinik St. Elisabeth, Heidelberg, Germany
- Medizinische Fakultät, Ruprecht-Karls-Universität Heidelberg, Heidelberg, Germany
| | - Jens Huober
- Brustzentrum, Kantonsspital St. Gallen, St. Gallen, Switzerland
| | - Christian Jackisch
- Klinik für Gynäkologie und Geburtshilfe, Sana-Klinikum Offenbach GmbH, Offenbach, Germany
| | | | | | - Sibylle Loibl
- German Breast Group (GBG), Neu-Isenburg, Germany
- Centrum für Hämatologie und Onkologie Bethanien, Frankfurt am Main, Germany
| | - Diana Lüftner
- Immanuel Klinik Märkische Schweiz, Buckow, Germany
- Immanuel Klinik Rüdersdorf, Medizinische Hochschule Brandenburg, Rüdersdorf/Berlin, Germany
| | - Marion van Mackelenbergh
- Gynäkologie und Geburtshilfe, Campus Kiel, Universitätsklinikum Schleswig-Holstein, Kiel, Germany
| | - Julia C Radosa
- Klinik für Gynäkologie, Geburtshilfe und Reproduktionsmedizin, Universitätsklinikum des Saarlandes, Homburg/Saar, Germany
| | - Toralf Reimer
- Universitätsfrauenklinik und Poliklinik, Klinikum Südstadt Rostock, Rostock, Germany
| | - Manfred Welslau
- Onkologie Aschaffenburg, Hämato-Onkologische Schwerpunktpraxis, Klinikum Aschaffenburg-Alzenau, Aschaffenburg, Germany
| | - Rachel Würstlein
- Brustzentrum, Frauenklinik, LMU Klinikum München, Munich, Germany
| | - Michael Untch
- Klinik für Gynäkologie und Geburtshilfe, interdisziplinäres Brustzentrum, HELIOS Klinikum Berlin Buch, Berlin, Germany
| | - Wilfried Budach
- Klinik für Strahlentherapie und Radioonkologie, Universitätsklinikum Düsseldorf, Düsseldorf, Germany
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10
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Saadatmand P, Mahdavi SR, Nikoofar A, Jazaeri SZ, Ramandi FL, Esmaili G, Vejdani S. A dosiomics model for prediction of radiation-induced acute skin toxicity in breast cancer patients: machine learning-based study for a closed bore linac. Eur J Med Res 2024; 29:282. [PMID: 38735974 PMCID: PMC11089719 DOI: 10.1186/s40001-024-01855-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2024] [Accepted: 04/23/2024] [Indexed: 05/14/2024] Open
Abstract
BACKGROUND Radiation induced acute skin toxicity (AST) is considered as a common side effect of breast radiation therapy. The goal of this study was to design dosiomics-based machine learning (ML) models for prediction of AST, to enable creating optimized treatment plans for high-risk individuals. METHODS Dosiomics features extracted using Pyradiomics tool (v3.0.1), along with treatment plan-derived dose volume histograms (DVHs), and patient-specific treatment-related (PTR) data of breast cancer patients were used for modeling. Clinical scoring was done using the Common Terminology Criteria for Adverse Events (CTCAE) V4.0 criteria for skin-specific symptoms. The 52 breast cancer patients were grouped into AST 2 + (CTCAE ≥ 2) and AST 2 - (CTCAE < 2) toxicity grades to facilitate AST modeling. They were randomly divided into training (70%) and testing (30%) cohorts. Multiple prediction models were assessed through multivariate analysis, incorporating different combinations of feature groups (dosiomics, DVH, and PTR) individually and collectively. In total, seven unique combinations, along with seven classification algorithms, were considered after feature selection. The performance of each model was evaluated on the test group using the area under the receiver operating characteristic curve (AUC) and f1-score. Accuracy, precision, and recall of each model were also studied. Statistical analysis involved features differences between AST 2 - and AST 2 + groups and cutoff value calculations. RESULTS Results showed that 44% of the patients developed AST 2 + after Tomotherapy. The dosiomics (DOS) model, developed using dosiomics features, exhibited a noteworthy improvement in AUC (up to 0.78), when spatial information is preserved in the dose distribution, compared to DVH features (up to 0.71). Furthermore, a baseline ML model created using only PTR features for comparison with DOS models showed the significance of dosiomics in early AST prediction. By employing the Extra Tree (ET) classifiers, the DOS + DVH + PTR model achieved a statistically significant improved performance in terms of AUC (0.83; 95% CI 0.71-0.90), accuracy (0.70), precision (0.74) and sensitivity (0.72) compared to other models. CONCLUSIONS This study confirmed the benefit of dosiomics-based ML in the prediction of AST. However, the combination of dosiomics, DVH, and PTR yields significant improvement in AST prediction. The results of this study provide the opportunity for timely interventions to prevent the occurrence of radiation induced AST.
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Affiliation(s)
- Pegah Saadatmand
- Department of Medical Physics, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Seied Rabi Mahdavi
- Department of Medical Physics, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
- Radiation Biology Research Center, Iran University of Medical Sciences, Tehran, Iran.
| | - Alireza Nikoofar
- Department of Radiation Oncology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Seyede Zohreh Jazaeri
- Department of Neuroscience, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran
- Division of NeuroscienceCellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran
| | | | | | - Soheil Vejdani
- Department of Radiation Oncology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
- Department of Radiation Oncology, Firoozgar Hospital, Iran University of Medical Sciences, Tehran, Iran
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11
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Busschaert SL, Kimpe E, Barbé K, De Ridder M, Putman K. Introduction of ultra-hypofractionation in breast cancer: Implications for costs and resource use. Radiother Oncol 2024; 190:110010. [PMID: 37956888 DOI: 10.1016/j.radonc.2023.110010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2023] [Revised: 10/14/2023] [Accepted: 11/04/2023] [Indexed: 11/15/2023]
Abstract
PURPOSE A shift towards (ultra-)hypofractionated breast irradiation can have important implications for the practice of contemporary radiation oncology. This paper presents a systematic analysis of the impact of different fractionation schedules on multiple key performance indicators, namely resource use, costs, work times, throughput and waiting times. MATERIALS AND METHODS Time-driven activity-based costing (TD-ABC) is applied to calculate the costs and resources consumed where the perspective of the radiotherapy department in adopted. Three fractionation regimens are considered: ultra-hypofractionation (5 x 5.2 Gy, UHF), moderate hypofractionation (15 x 2.67 Gy, HF) and conventional fractionation (25 x 2 Gy, CF). Subsequently, a discrete event simulation (DES) model of the radiotherapy care pathway is developed and scenarios are compared in which the following factors are varied: distribution of fractionation regimens, patient volume and operating hours. RESULTS The application of (U)HF can permit radiotherapy departments to reduce the use of scarce resources, realise work time and cost savings, increase throughput and reduce waiting times. The financial advantages of (U)HF are, however, reduced in cases of excess capacity and cost savings may therefore be limited in the short-term. Moreover, although an extension of operating hours has favourable effects on throughput and waiting times, it may also reduce cost differences between fractionation schedules by increasing the capacity of resources. CONCLUSION By providing an in-depth analysis of the consequences associated with a shift towards (U)HF in breast cancer, the present study demonstrates how a DES model based on TD-ABC costing can assist radiotherapy professionals in making data-driven decisions.
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Affiliation(s)
- Sara-Lise Busschaert
- Department of Public Health, Vrije Universiteit Brussel, Laarbeeklaan, 101 - 1090 Brussels, Belgium.
| | - Eva Kimpe
- Department of Public Health, Vrije Universiteit Brussel, Laarbeeklaan, 101 - 1090 Brussels, Belgium
| | - Kurt Barbé
- Department of Public Health, Vrije Universiteit Brussel, Laarbeeklaan, 101 - 1090 Brussels, Belgium
| | - Mark De Ridder
- Department of Radiotherapy, Universitair Ziekenhuis Brussel, Laarbeeklaan, 101 - 1090 Brussels, Belgium
| | - Koen Putman
- Department of Public Health, Vrije Universiteit Brussel, Laarbeeklaan, 101 - 1090 Brussels, Belgium; Department of Radiotherapy, Universitair Ziekenhuis Brussel, Laarbeeklaan, 101 - 1090 Brussels, Belgium
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12
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Mast M, Leong A, Korreman S, Lee G, Probst H, Scherer P, Tsang Y. ESTRO-ACROP guideline for positioning, immobilisation and setup verification for local and loco-regional photon breast cancer irradiation. Tech Innov Patient Support Radiat Oncol 2023; 28:100219. [PMID: 37745181 PMCID: PMC10511493 DOI: 10.1016/j.tipsro.2023.100219] [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: 09/10/2023] [Accepted: 09/10/2023] [Indexed: 09/26/2023] Open
Affiliation(s)
- M.E. Mast
- Department of Radiation Oncology, Haaglanden Medical Center, Leidschendam, The Netherlands
| | - A. Leong
- Department of Radiation Therapy, University of Otago, Wellington, New Zealand
- Bowen Icon Cancer Centre, Wellington, New Zealand
| | - S.S. Korreman
- Department of Clinical Medicine, Aarhus University, Denmark
- Department of Oncology, Aarhus University Hospital, Denmark
- Danish Center for Particle Therapy, Aarhus University Hospital, Denmark
| | - G. Lee
- Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Canada
- Department of Radiation Oncology, University of Toronto, Toronto, Canada
| | - H. Probst
- Sheffield Hallam University, Sheffield, United Kingdom
| | - P. Scherer
- Department of Radiotherapy and Radio-Oncology, LKH Salzburg, Paracelsus Medical University Clinics, Salzburg, Austria
| | - Y. Tsang
- Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Canada
- Department of Radiation Oncology, University of Toronto, Toronto, Canada
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13
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Banys-Paluchowski M, Hartmann S, Ditsch N, Krawczyk N, Kühn T, de Boniface J, Banys-Kotomska J, Rody A, Krug D. Locoregional Therapy: From Mastectomy to Reconstruction, Targeted Surgery, and Ultra-Hypofractionated Radiotherapy. Breast Care (Basel) 2023; 18:428-439. [PMID: 38130814 PMCID: PMC10731028 DOI: 10.1159/000533748] [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: 04/25/2023] [Accepted: 08/21/2023] [Indexed: 12/23/2023] Open
Abstract
Background The past 3 decades have seen an unprecedented shift toward treatment de-escalation in surgical therapy of breast cancer. Summary Radical mastectomy has been replaced by breast-conserving and oncoplastic approaches in most patients, and full axillary lymph node dissection by less radical staging procedures, such as sentinel lymph node biopsy and targeted axillary dissection. Further, attempts have been made to spare healthy tissue while increasing the probability of removing the tumor with clear margins, thus improving cosmetic results and minimizing the risk of local recurrence. In this context, modern probe-guided localization techniques have been introduced to guide surgical excision. This progress was accompanied by the development of targeted systemic therapies. At the same time, radiotherapy for breast cancer has undergone significant changes. The use of hypofractionation has decreased the typical length of a treatment course from 5-6 weeks to 1-3 weeks. Partial breast irradiation is now a valid option for de-escalation in patients with low-risk features. Axillary radiotherapy achieves similar recurrence rates and decreases the risk of lymphedema in patients with limited sentinel node involvement. Key Messages Taken together, these advances are important steps toward individualization of locoregional management strategies. This highlights the importance of interdisciplinary approaches for de-escalation of locoregional therapies.
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Affiliation(s)
- Maggie Banys-Paluchowski
- Department of Gynecology and Obstetrics, University Hospital Schleswig-Holstein, Campus Lubeck, Lubeck, Germany
| | - Steffi Hartmann
- Department of Gynecology and Obstetrics, University Hospital Rostock, Rostock, Germany
| | - Nina Ditsch
- Breast Cancer Center, Department of Gynaecology and Obstetrics, University Hospital Augsburg, Augsburg, Germany
| | - Natalia Krawczyk
- Department of Gynecology and Obstetrics, Heinrich-Heine-University Düsseldorf, Dusseldorf, Germany
| | - Thorsten Kühn
- Department of Gynecology and Obstetrics, Die Filderklinik, Filderstadt, Germany
| | - Jana de Boniface
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
- Department of Surgery, Capio St. Göran’s Hospital, Stockholm, Sweden
| | - Joanna Banys-Kotomska
- I Department and Clinic of Gynaecology and Obstetrics, Wroclaw Medical University, Wroclaw, Poland
| | - Achim Rody
- Department of Gynecology and Obstetrics, University Hospital Schleswig-Holstein, Campus Lubeck, Lubeck, Germany
| | - David Krug
- Department of Radiation Oncology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany
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14
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Krug D, Dunst J. [Moderate hypofractionated adjuvant radiotherapy with simultaneous integrated boost for breast cancer]. Strahlenther Onkol 2023; 199:1033-1035. [PMID: 37698593 PMCID: PMC10598182 DOI: 10.1007/s00066-023-02144-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/16/2023] [Indexed: 09/13/2023]
Affiliation(s)
- David Krug
- Klinik für Strahlentherapie/Radioonkologie, UKSH, Campus Kiel, Kiel, Deutschland
| | - Jürgen Dunst
- Klinik für Strahlentherapie/Radioonkologie, UKSH, Campus Kiel, Kiel, Deutschland.
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15
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Chen K, Sun W, Han T, Yan L, Sun M, Xia W, Wang L, Shi Y, Ge C, Yang X, Li Y, Wang H. Robustness of hypofractionated breast radiotherapy after breast-conserving surgery with free breathing. Front Oncol 2023; 13:1259851. [PMID: 38023210 PMCID: PMC10644368 DOI: 10.3389/fonc.2023.1259851] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2023] [Accepted: 10/17/2023] [Indexed: 12/01/2023] Open
Abstract
Purpose This study aimed to evaluate the robustness with respect to the positional variations of five planning strategies in free-breathing breast hypofractionated radiotherapy (HFRT) for patients after breast-conserving surgery. Methods Twenty patients who received breast HFRT with 42.72 Gy in 16 fractions were retrospectively analyzed. Five treatment planning strategies were utilized for each patient, including 1) intensity-modulated radiation therapy (IMRT) planning (IMRTpure); 2) IMRT planning with skin flash tool extending and filling the fluence outside the skin by 2 cm (IMRTflash); 3) IMRT planning with planning target volume (PTV) extended outside the skin by 2 cm in the computed tomography dataset (IMRTePTV); 4) hybrid planning, i.e., 2 Gy/fraction three-dimensional conformal radiation therapy combined with 0.67 Gy/fraction IMRT (IMRThybrid); and 5) hybrid planning with skin flash (IMRThybrid-flash). All plans were normalized to 95% PTV receiving 100% of the prescription dose. Six additional plans were created with different isocenter shifts for each plan, which were 1 mm, 2 mm, 3 mm, 5 mm, 7 mm, and 10 mm distally in the X (left-right) and Y (anterior-posterior) directions, namely, (X,Y), to assess their robustness, and the corresponding doses were recalculated. Variation of dosimetric parameters with increasing isocenter shift was evaluated. Results All plans were clinically acceptable. In terms of robustness to isocenter shifts, the five planning strategies followed the pattern IMRTePTV, IMRThybrid-flash, IMRTflash, IMRThybrid, and IMRTpure in descending order. V 95% of IMRTePTV maintained at 99.6% ± 0.3% with a (5,5) shift, which further reduced to 98.2% ± 2.0% with a (10,10) shift. IMRThybrid-flash yielded the robustness second to IMRTePTV with less risk from dose hotspots, and the corresponding V 95% maintained >95% up until (5,5). Conclusion Considering the dosimetric distribution and robustness in breast radiotherapy, IMRTePTV performed best at maintaining high target coverage with increasing isocenter shift, while IMRThybrid-flash would be adequate with positional uncertainty<5 mm.
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Affiliation(s)
- Kunzhi Chen
- Department of Radiation Oncology & Therapy, The First Hospital of Jilin University, Changchun, China
| | - Wuji Sun
- Department of Radiation Oncology & Therapy, The First Hospital of Jilin University, Changchun, China
| | - Tao Han
- Department of Radiation Oncology & Therapy, The First Hospital of Jilin University, Changchun, China
| | - Lei Yan
- Department of Radiation Oncology & Therapy, The First Hospital of Jilin University, Changchun, China
| | - Minghui Sun
- Department of Radiation Oncology & Therapy, The First Hospital of Jilin University, Changchun, China
| | - Wenming Xia
- Department of Radiation Oncology & Therapy, The First Hospital of Jilin University, Changchun, China
| | - Libo Wang
- Department of Radiation Oncology & Therapy, The First Hospital of Jilin University, Changchun, China
| | - Yinghua Shi
- Department of Radiation Oncology & Therapy, The First Hospital of Jilin University, Changchun, China
| | - Chao Ge
- Department of Radiation Oncology & Therapy, The First Hospital of Jilin University, Changchun, China
| | - Xu Yang
- Department of Radiation Oncology & Therapy, The First Hospital of Jilin University, Changchun, China
| | - Yu Li
- Department of Radiation Oncology & Therapy, The First Hospital of Jilin University, Changchun, China
| | - Huidong Wang
- Department of Radiation Oncology & Therapy, The First Hospital of Jilin University, Changchun, China
- Jilin Provincial Key Laboratory of Radiation Oncology & Therapy, Department of Radiation Oncology & Therapy, The First Hospital of Jilin University, Changchun, China
- NHC Key Laboratory of Radiobiology, School of Public Health, Jilin University, Changchun, China
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16
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Fabian A, Rühle A, Domschikowski J, Trommer M, Wegen S, Becker JN, Wurschi G, Boeke S, Sonnhoff M, Fink CA, Käsmann L, Schneider M, Bockelmann E, Treppner M, Mehnert-Theuerkauf A, Krug D, Nicolay NH. Psychosocial distress in cancer patients undergoing radiotherapy: a prospective national cohort of 1042 patients in Germany. J Cancer Res Clin Oncol 2023; 149:9017-9024. [PMID: 37165119 PMCID: PMC10374761 DOI: 10.1007/s00432-023-04837-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2023] [Accepted: 05/02/2023] [Indexed: 05/12/2023]
Abstract
PURPOSE Psychosocial distress is common among cancer patients in general, but those undergoing radiotherapy may face specific challenges. Therefore, we investigated the prevalence and risk factors for distress in a large national cohort. METHODS We performed a secondary analysis of a multicenter prospective cross-sectional study which surveyed cancer patients at the end of a course of radiotherapy using a patient-reported questionnaire. Distress was measured with the distress thermometer (DT), using a cut-off of ≥ 5 points for clinically significant distress. Univariate analyses and multivariate multiple regression were used to assess associations of distress with patient characteristics. A two-sided p-value < 0.05 was considered statistically significant. RESULTS Out of 2341 potentially eligible patients, 1075 participated in the study, of which 1042 completed the DT. The median age was 65 years and 49% (511/1042) of patients were female. The mean DT score was 5.2 (SD = 2.6). Clinically significant distress was reported by 63% (766/1042) of patients. Of the patient characteristics that were significantly associated with distress in the univariate analysis, a lower level of education, a higher degree of income loss, lower global quality of life, and a longer duration of radiotherapy in days remained significantly associated with higher distress in the multivariate analysis. Yet effect sizes of these associations were small. CONCLUSION Nearly two in three cancer patients undergoing radiotherapy reported clinically significant distress in a large multicenter cohort. While screening and interventions to reduce distress should be maintained and promoted, the identified risk factors may help to raise awareness in clinical practice. TRIAL REGISTRY IDENTIFIER DRKS: German Clinical Trial Registry identifier: DRKS00028784.
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Affiliation(s)
- Alexander Fabian
- Department of Radiation Oncology, University Hospital Schleswig-Holstein, Arnold-Heller-Str. 3, 24105, Kiel, Germany.
| | - Alexander Rühle
- Department of Radiation Oncology, Medical Center, Faculty of Medicine, University of Freiburg, 79106, Freiburg, Germany
- Department of Radiotherapy and Radiation Oncology, University Hospital Leipzig, 04103, Leipzig, Germany
| | - Justus Domschikowski
- Department of Radiation Oncology, University Hospital Schleswig-Holstein, Arnold-Heller-Str. 3, 24105, Kiel, Germany
| | - Maike Trommer
- Department of Radiation Oncology, Cyberknife and Radiotherapy, Faculty of Medicine and University Hospital Cologne, 50937, Cologne, Germany
- Center for Molecular Medicine Cologne, University of Cologne, 50931, Cologne, Germany
| | - Simone Wegen
- Department of Radiation Oncology, Cyberknife and Radiotherapy, Faculty of Medicine and University Hospital Cologne, 50937, Cologne, Germany
| | - Jan-Niklas Becker
- Department of Radiotherapy and Special Oncology, Medical School Hannover, 30625, Hannover, Germany
| | - Georg Wurschi
- Department of Radiotherapy and Radiation Oncology, Jena University Hospital, 07740, Jena, Germany
| | - Simon Boeke
- Department of Radiation Oncology, University Hospital Tübingen, 72076, Tübingen, Germany
| | - Mathias Sonnhoff
- Center for Radiotherapy and Radiation Oncology, 28239, Bremen, Germany
| | - Christoph A Fink
- Department of Radiation Oncology, University Hospital Heidelberg, 69120, Heidelberg, Germany
| | - Lukas Käsmann
- Department of Radiation Oncology, University Hospital, LMU Munich, 81377, Munich, Germany
- Comprehensive Pneumology Center Munich (CPC-M), Member of the German Center for Lung Research (DZL), 81377, Munich, Germany
- German Cancer Consortium (DKTK), Partner Site Munich, 81377, Munich, Germany
| | - Melanie Schneider
- Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, 01307, Dresden, Germany
| | - Elodie Bockelmann
- Department of Radiotherapy and Radiation Oncology, University Hospital Hamburg-Eppendorf, 20251, Hamburg, Germany
| | - Martin Treppner
- Institute of Medical Biometry and Statistics, University Hospital Freiburg, 79106, Freiburg, Germany
| | - Anja Mehnert-Theuerkauf
- Department of Medical Psychology and Medical Sociology, University Medical Center Leipzig, 04103, Leipzig, Germany
| | - David Krug
- Department of Radiation Oncology, University Hospital Schleswig-Holstein, Arnold-Heller-Str. 3, 24105, Kiel, Germany
| | - Nils H Nicolay
- Department of Radiotherapy and Radiation Oncology, University Hospital Leipzig, 04103, Leipzig, Germany
- Cancer Center Central Germany, Partner Site Leipzig, 04103, Leipzig, Germany
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Omosule M, De Silva-Minor S, Coombs N. Case Report: Intraoperative radiotherapy as the new standard of care for breast cancer patients with disabling health conditions or impairments. Front Oncol 2023; 13:1156619. [PMID: 37274260 PMCID: PMC10233125 DOI: 10.3389/fonc.2023.1156619] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2023] [Accepted: 05/03/2023] [Indexed: 06/06/2023] Open
Abstract
In selected patients, intraoperative radiotherapy (IORT) offers an alternative to standard external beam radiotherapy (EBRT) while providing equivalent breast cancer control outcomes. After IORT, most patients do not require external beam radiotherapy and thus avoid the need to travel to and from a radiotherapy centre in the weeks after surgery. EBRT is associated with an increased risk of non-breast cancer mortality and poorer cosmetic outcomes while increasing patient travel time, emissions associated with travel and time spent in the hospital. Consequently, EBRT is associated with an overall reduction in quality of life compared to IORT. Patients with other on-going health conditions or clinical impairments are likely to be affected by the daily radiotherapy requirement. Should these patients be consulted during their pre-operative assessment as to options to undergo IORT? This paper describes a case of IORT and follow up in a functionally blind patient. Quality of life effects are elucidated and further support the use of IORT in selected breast cancer patients with health conditions or impairments.
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Affiliation(s)
- Michael Omosule
- GKT School of Medical Education, King’s College London, London, United Kingdom
| | - Shiroma De Silva-Minor
- Department of Clinical Oncology, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom
| | - Nathan Coombs
- Department of Breast Surgery, Great Western Hospitals NHS Foundation Trust, Great Western Hospital, Swindon, United Kingdom
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Knippen S, Schönherr S, Schwedas M, Teichmann T, Howitz S, Mäurer M, Wittig-Sauerwein A, Duma MN. Low doses to the heart in daily practice for treating left-sided breast cancer using accelerated partial-breast irradiation by multicatheter brachytherapy and deep-inspiration breath-hold using a SIB. Strahlenther Onkol 2023; 199:389-395. [PMID: 36826517 PMCID: PMC10033472 DOI: 10.1007/s00066-023-02047-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2022] [Accepted: 01/15/2023] [Indexed: 02/25/2023]
Abstract
PURPOSE The aim of this study was to analyze the heart dose for left-sided breast cancer that can be achieved during daily practice in patients treated with multicatheter brachytherapy (MCBT) accelerated partial-breast irradiation (APBI) and deep-inspiration breath-hold (DIBH) whole-breast irradiation (WBI) using a simultaneous integrated tumor bed boost (SIB)-two different concepts which nonetheless share some patient overlap. MATERIALS AND METHODS We analyzed the nominal average dose (Dmean) to the heart as well as the biologically effective dose (BED) and the equivalent dose in 2‑Gy fractions (EQD2) for an α/β of 3 in 30 MCBT-APBI patients and 22 patients treated with DIBH plus SIB. For further dosimetric comparison, we contoured the breast planning target volume (PTV) in each of the brachytherapy planning CTs according to the ESTRO guidelines and computed tangential field plans. Mean dose (Dmean), EQD2 Dmean, and BED Dmean for three dosing schemes were calculated: 50 Gy/25 fractions and two hypofractionated regimens, i.e., 40.05 Gy/15 fractions and 26 Gy/5 fractions. Furthermore, we calculated tangential field plans without a boost for the 22 cases treated with SIB with the standard dosing scheme of 40.05 Gy/15 fractions. RESULTS MCBT and DIBH radiation therapy both show low-dose exposure of the heart. As expected, hypofractionation leads to sparing of the heart dose. Although MCBT plans were not optimized regarding dose to the heart, Dmean differed significantly between MCBT and DIBH (1.28 Gy vs. 1.91 Gy, p < 0.001) in favor of MCBT, even if the Dmean in each group was very low. In MCBT radiation, the PTV-heart distance is significantly associated with the dose to the heart (p < 0.001), but it is not in DIBH radiotherapy using SIB. CONCLUSION In daily practice, both DIBH radiation therapy as well as MCBT show a very low heart exposure and may thus reduce long term cardiac morbidity as compared to currently available long-term clinical data of patients treated with conventional tangential field plans in free breathing. Our analysis confirms particularly good cardiac sparing with MCBT-APBI, so that this technique should be offered to patients with left-sided breast cancer if the tumor-associated eligibility criteria are fulfilled.
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Affiliation(s)
- Stefan Knippen
- Department of Radiotherapy and Radiation Oncology, University Hospital Jena, Friedrich Schiller University, Jena, Germany.
- Department of Radiation Oncology, Helios Kliniken Schwerin - University Campus of MSH Medical School Hamburg, Schwerin, Germany.
| | - Sven Schönherr
- Department of Radiotherapy and Radiation Oncology, University Hospital Jena, Friedrich Schiller University, Jena, Germany
| | - Michael Schwedas
- Department of Radiotherapy and Radiation Oncology, University Hospital Jena, Friedrich Schiller University, Jena, Germany
| | - Tobias Teichmann
- Department of Radiotherapy and Radiation Oncology, University Hospital Jena, Friedrich Schiller University, Jena, Germany
| | - Simon Howitz
- Department of Radiotherapy and Radiation Oncology, University Hospital Jena, Friedrich Schiller University, Jena, Germany
- Department of Radiation Oncology, SRH Wald-Klinikum Gera, Gera, Germany
| | - Matthias Mäurer
- Department of Radiotherapy and Radiation Oncology, University Hospital Jena, Friedrich Schiller University, Jena, Germany
| | - Andrea Wittig-Sauerwein
- Department of Radiotherapy and Radiation Oncology, University Hospital Jena, Friedrich Schiller University, Jena, Germany
| | - Marciana-Nona Duma
- Department of Radiotherapy and Radiation Oncology, University Hospital Jena, Friedrich Schiller University, Jena, Germany
- Department of Radiation Oncology, Helios Kliniken Schwerin - University Campus of MSH Medical School Hamburg, Schwerin, Germany
- MSH Medical School Hamburg, Department for Human Medicine, Hamburg, Germany
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19
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Köpke MM, Aktas B, Ditsch N. Recommendations for the diagnosis and treatment of patients with early breast cancer: update 2023. Curr Opin Obstet Gynecol 2023; 35:67-72. [PMID: 36595649 DOI: 10.1097/gco.0000000000000835] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
PURPOSE OF REVIEW In recent years, the therapy of breast carcinoma has evolved at a rapid pace. Therapies from metastasis are pushing into the (neo)adjuvant treatment of breast carcinoma at ever shorter intervals. RECENT FINDINGS Biomarker-based therapeutic approaches became more and more en vogue to guide (neo)adjuvant endocrine therapy and chemotherapy. SUMMARY This article reviews recent data developments in early breast cancer (EBC) and current recommendations in diagnosis and therapy.
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Gehre S, Meyer F, Sengedorj A, Grottker F, Reichardt CM, Alomo J, Borgmann K, Frey B, Fietkau R, Rückert M, Gaipl US. Clonogenicity-based radioresistance determines the expression of immune suppressive immune checkpoint molecules after hypofractionated irradiation of MDA-MB-231 triple-negative breast cancer cells. Front Oncol 2023; 13:981239. [PMID: 37152024 PMCID: PMC10157086 DOI: 10.3389/fonc.2023.981239] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2022] [Accepted: 03/28/2023] [Indexed: 05/09/2023] Open
Abstract
Only a subset of patients with triple-negative breast cancer (TNBC) benefits from a combination of radio- (RT) and immunotherapy. Therefore, we aimed to examine the impact of radioresistance and brain metastasizing potential on the immunological phenotype of TNBC cells following hypofractionated RT by analyzing cell death, immune checkpoint molecule (ICM) expression and activation of human monocyte-derived dendritic cells (DCs). MDA-MB-231 triple-negative breast cancer tumor cells were used as model system. Apoptosis was the dominant cell death form of brain metastasizing tumor cells, while Hsp70 release was generally significantly increased following RT and went along with necrosis induction. The ICMs PD-L1, PD-L2, HVEM, ICOS-L, CD137-L and OX40-L were found on the tumor cell surfaces and were significantly upregulated by RT with 5 x 5.2 Gy. Strikingly, the expression of immune suppressive ICMs was significantly higher on radioresistant clones compared to their respective non-radioresistant ones. Although hypofractionated RT led to significant cell death induction and release of Hsp70 in all tumor cell lines, human monocyte-derived DCs were not activated after co-incubation with RT-treated tumor cells. We conclude that radioresistance is a potent driver of immune suppressive ICM expression on the surface of TNBC MDA-MB-231 cells. This mechanism is generally known to predominantly influence the effector phase, rather than the priming phase, of anti-tumor immune responses.
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Affiliation(s)
- Simon Gehre
- Translational Radiobiology, Department of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
- Department of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
- Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany
| | - Felix Meyer
- Laboratory of Radiobiology and Experimental Radiooncology, Department of Radiotherapy and Radiation Oncology, Center of Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Azzaya Sengedorj
- Translational Radiobiology, Department of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
- Department of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
- Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany
| | - Fridolin Grottker
- Translational Radiobiology, Department of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
- Department of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
- Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany
| | - Clara M. Reichardt
- Translational Radiobiology, Department of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
- Department of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
- Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany
| | - Jannik Alomo
- Translational Radiobiology, Department of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
- Department of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
- Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany
| | - Kerstin Borgmann
- Laboratory of Radiobiology and Experimental Radiooncology, Department of Radiotherapy and Radiation Oncology, Center of Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Benjamin Frey
- Translational Radiobiology, Department of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
- Department of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
- Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany
| | - Rainer Fietkau
- Department of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
- Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany
| | - Michael Rückert
- Translational Radiobiology, Department of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
- Department of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
- Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany
| | - Udo S. Gaipl
- Translational Radiobiology, Department of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
- Department of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
- Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany
- *Correspondence: Udo S. Gaipl,
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Offersen BV, Alsner J, Nielsen HM, Jakobsen EH, Nielsen MH, Stenbygaard L, Pedersen AN, Thomsen MS, Yates E, Berg M, Lorenzen EL, Jensen I, Josipovic M, Jensen MB, Overgaard J. Partial Breast Irradiation Versus Whole Breast Irradiation for Early Breast Cancer Patients in a Randomized Phase III Trial: The Danish Breast Cancer Group Partial Breast Irradiation Trial. J Clin Oncol 2022; 40:4189-4197. [PMID: 35930754 DOI: 10.1200/jco.22.00451] [Citation(s) in RCA: 48] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
PURPOSE On the basis of low risk of local recurrence in elderly patients with breast cancer after conservative surgery followed by whole breast irradiation (WBI), the Danish Breast Cancer Group initiated the noninferiority external-beam partial breast irradiation (PBI) trial (ClinicalTrials.gov identifier: NCT00892814). We hypothesized that PBI was noninferior to WBI regarding breast induration. METHODS Patients operated with breast conservation for relatively low-risk breast cancer were randomly assigned to WBI versus PBI, and all had 40 Gy/15 fractions. The primary end point was 3-year grade 2-3 breast induration. RESULTS In total, 865 evaluable patients (434 WBI and 431 PBI) were enrolled between 2009 and 2016. Median follow-up was 5.0 years (morbidity) and 7.6 years (locoregional recurrence). The 3-year rate of induration was 9.7% for WBI and 5.1% for PBI (P = .014). Large breast size was significantly associated with induration with a 3-year incidence of 13% (WBI) and 6% (PBI) for large-breasted patients versus 6% (WBI) and 5% (PBI) for small-breasted patients. PBI showed no increased risk of dyspigmentation, telangiectasia, edema, or pain, and patient satisfaction was high. Letrozole and smoking did not increase the risk of radiation-associated morbidity. Sixteen patients had a locoregional recurrence (six WBI and 10 PBI; P = .28), 20 patients had a contralateral breast cancer, and eight patients had distant failure (five WBI and three PBI). A nonbreast second cancer was detected in 73 patients (8.4%), and there was no difference between groups. CONCLUSION External-beam PBI for patients with low-risk breast cancer was noninferior to WBI in terms of breast induration. Large breast size was a risk factor for radiation-associated induration. Few recurrences were detected and unrelated to PBI.
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Affiliation(s)
- Birgitte V Offersen
- Department of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark.,Department of Oncology, Aarhus University Hospital, Aarhus, Denmark
| | - Jan Alsner
- Department of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark
| | - Hanne M Nielsen
- Department of Oncology, Aarhus University Hospital, Aarhus, Denmark
| | | | - Mette H Nielsen
- Department of Oncology, Odense University Hospital, Odense, Denmark
| | - Lars Stenbygaard
- Department of Oncology, Aalborg University Hospital, Aalborg, Denmark
| | - Anders N Pedersen
- Department of Oncology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - Mette S Thomsen
- Department of Medical Physics, Aarhus University Hospital, Aarhus, Denmark
| | - Esben Yates
- Department of Medical Physics, Aarhus University Hospital, Aarhus, Denmark
| | - Martin Berg
- Department of Medical Physics, Lillebaelt Hospital, Vejle, Denmark
| | - Ebbe L Lorenzen
- Department of Oncology, Odense University Hospital, Odense, Denmark
| | - Ingelise Jensen
- Department of Medical Physics, Aalborg University Hospital, Aalborg, Denmark
| | - Mirjana Josipovic
- Department of Oncology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - Maj-Britt Jensen
- Danish Breast Cancer Group, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - Jens Overgaard
- Department of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark
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Ahmad A, Das S, Kharade V, Gupta M, Pandey V, K.V. A, Balasubramanian I, Pasricha RK. Dosimetric Study Comparing 3D Conformal Radiotherapy (3D-CRT), Intensity Modulated Radiotherapy (IMRT) and Volumetric Modulated Arc Therapy (VMAT) in Hypofractionated One-Week Radiotherapy Regimen in Breast Cancer. Cureus 2022; 14:e31860. [PMID: 36440297 PMCID: PMC9691918 DOI: 10.7759/cureus.31860] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/24/2022] [Indexed: 11/25/2022] Open
Abstract
Introduction Recently, the one-week hypofractionated radiotherapy regimen (26 Gy in 5 fractions) for adjuvant breast radiotherapy has been shown to be non-inferior to other hypofractionated regimens (15-16 fractions). The aim of the present dosimetric study is to compare Intensity Modulated Radiotherapy (IMRT), Volumetric Modulated Arc Therapy (VMAT) and 3D Conformal Radiotherapy (3D-CRT) for a one-week hypofractionated radiotherapy regimen (26 Gy in 5 fractions) for adjuvant breast radiotherapy. Methods A total of 30 patients with histologically proven invasive carcinoma of the breast after breast conservation surgery (BCS) or modified radical mastectomy (MRM) were considered for in silico planning study. The dose prescription used was 26 Gy in 5 fractions as used in the FAST Forward protocol. Targets were contoured according to standard guidelines. The heart, ipsilateral lung, and contralateral breast were contoured as organs at risk. Results Planning Target Volume (PTV) coverage: For IMRT, VMAT and 3D-CRT, respectively, the volumes that received at least 95% of the prescription dose (V95) were 95.7 ± 2.12, 92.47 ± 3.83, 90.87 ± 5.13; mean PTV doses (Dmean) were 26.1 ± 0.6, 25.7 ± 0.7, and 28 ± 4.39 (3D-CRT has higher Dmean compared to other techniques). Maximum PTV doses (Dmax) were 28.23 ± 0.72, 28.73 ± 0.64, and 29.8 ± 1.03. IMRT had a better V95 coverage and conformity index. Organs At Risk (OARs): The volumes that received at least 25% of the prescription dose (V25) of the heart were 3.41 ± 4.7, 1.8 ± 2.02 and 4.3 ± 6.98 in IMRT, VMAT and 3D-CRT, respectively. The volumetric (V25) comparison of heart dose in left-sided breast cancer was significantly different between VMAT and 3D-CRT (p=0.04, Wilcoxon signed-rank test). The volume that received at least 5% of the prescription dose (V5 ) was less than 25% in the 3D-CRT plan (12.55). For the ipsilateral lung, the V25 parameters were 19.53 ± 10.96, 23.93 ± 13.58 and 20.5 ± 12.32 in IMRT, VMAT and 3D-CRT, respectively. Conclusion From this study, we can conclude that IMRT and VMAT techniques are feasible and can achieve better dosimetric goals for target and OARs though minimizing the area achieving low dose remains to be a dosimetric concern for VMAT.
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23
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Bauer A. Radiation Treatment for Breast Cancer. Surg Clin North Am 2022; 103:187-199. [DOI: 10.1016/j.suc.2022.08.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
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Les essais qui changent les pratiques : le point en 2022. Cancer Radiother 2022; 26:823-833. [DOI: 10.1016/j.canrad.2022.07.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2022] [Accepted: 07/06/2022] [Indexed: 11/19/2022]
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25
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Abolaban FA. Review of recent impacts of artificial intelligence for radiation therapy procedures. Radiat Phys Chem Oxf Engl 1993 2022. [DOI: 10.1016/j.radphyschem.2022.110469] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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Chakraborty S, Chatterjee S. HYPORT adjuvant acute toxicity and patient dosimetry quality assurance results - Interim analysis. Radiother Oncol 2022; 174:59-68. [PMID: 35817323 DOI: 10.1016/j.radonc.2022.07.003] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2022] [Revised: 06/21/2022] [Accepted: 07/01/2022] [Indexed: 12/20/2022]
Abstract
BACKGROUND HYPORT adjuvant trial is a randomised phase III open-label noninferiority trial comparing standard moderately hypofractionated 3 week adjuvant radiation therapy in breast cancer with a novel 1-week schedule. The trial was initiated in March 2019 and is open to recruitment with a total sample size of 2100. We report the results of dosimetric quality assurance, acute toxicity and pre planned first interim safety analysis in the first 271 patients. METHODS Stage I-III breast cancer planned for adjuvant radiation therapy to the breast/chest-wall (along with regional nodes as indicated) were randomised to receive 40 Gy/15 fractions/3 weeks or 26 Gy/5 fractions/1 week. For simultaneous integrated boost, the patients in the control arm received 8 Gy/15 fractions/3 weeks, while those in the experimental arm received 6 Gy/5 fractions/1 week (to the tumour bed). For sequential boost, the prescribed dose was 12 Gy/4 fractions/4 days in both arms. Compliance to pre specified dosimetric parameters and acute toxicities were evaluated. RESULT Data of the first 271 patients was analysed of whom 104 patients received tumour bed boost using SIB. All mandatory dosimetric criteria were met apart from one patient with a higher contralateral breast dose due to optimal internal mammary nodal coverage. Overall three patients (1.1%) experienced grade 3 radiation dermatitis (none received SIB), no other Grade 3 or higher toxicities reported. CONCLUSION This acute toxicity interim analysis demonstrates that hypofractionated adjuvant radiotherapy with SIB for patients with breast cancer is feasible, and associated with minimal severe acute toxicities.
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Xia C, Qin L, Wang Y, Yao L, Shia B, Wu SY. Risk factors and specific cancer types of second primary malignancies in patients with breast cancer receiving adjuvant radiotherapy: a case-control cohort study based on the SEER database. Am J Cancer Res 2022; 12:2744-2756. [PMID: 35812050 PMCID: PMC9251704] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2022] [Accepted: 05/14/2022] [Indexed: 06/15/2023] Open
Abstract
Patients with breast cancer can survive and live a long, cancer-free life; however, late complications of treatment, such as second primary malignancies (SPMs), have emerged as a competing cause of death and morbidity. We conducted a long-term population-based cohort study to identify the risk factors for SPMs and specific secondary cancer types after various latency periods of irradiated breast cancer. Cox proportional hazards regression was used to calculate the hazard ratio (HR) and 95% confidence interval (95% CI) for independent risk factors for SPM. We also calculated the HR of each specific cancer type and the latency time to specific SPMs. The risk of SPM was statistically significantly higher in patients with adjuvant RT than in patients without adjuvant RT (adjusted HR [aHR]: 1.105, 95% CI: 1.013-1.206). Compared with the control group, the case group had significantly increased risks of contralateral breast cancer (aHR: 1.268, 95% CI: 1.112-1.445), lung cancer (aHR: 1.218, 95% CI: 1.049-1.565), and urinary system cancer (aHR: 1.702, 95% CI: 1.140-2.543). Adjuvant RT for breast cancer increases the risk of SPM. Contralateral breast cancer, lung cancer, and bladder cancer were significant SPMs after breast RT, although the cumulative risk of SPM was low, at approximately 6, 10, and 13 cancers per 1000 women with irradiated breasts at latency periods of 5, 10, and 15 years, respectively, after breast RT.
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Affiliation(s)
- Chuanxin Xia
- Chinese Academy of International Trade and Economic CooperationDongcheng, Beijing, China
| | - Lei Qin
- School of Statistics, University of International Business and EconomicsBeijing, China
| | - Yinzhi Wang
- School of Statistics, University of International Business and EconomicsBeijing, China
| | - Ling Yao
- Chinese Academy of International Trade and Economic CooperationDongcheng, Beijing, China
| | - Benchang Shia
- Graduate Institute of Business Administration, College of Management, Fu Jen Catholic UniversityNew Taipei City, Taiwan
- Artificial Intelligence Development Center, Fu Jen Catholic UniversityNew Taipei City, Taiwan
| | - Szu-Yuan Wu
- Graduate Institute of Business Administration, College of Management, Fu Jen Catholic UniversityNew Taipei City, Taiwan
- Artificial Intelligence Development Center, Fu Jen Catholic UniversityNew Taipei City, Taiwan
- Department of Food Nutrition and Health Biotechnology, College of Medical and Health Science, Asia UniversityTaichung, Taiwan
- Big Data Center, Lo-Hsu Medical Foundation, Lotung Poh-Ai HospitalYilan, Taiwan
- Division of Radiation Oncology, Lo-Hsu Medical Foundation, Lotung Poh-Ai HospitalYilan, Taiwan
- Department of Healthcare Administration, College of Medical and Health Science, Asia UniversityTaichung, Taiwan
- Centers for Regional Anesthesia and Pain Medicine, Taipei Municipal Wan Fang Hospital, Taipei Medical UniversityTaipei, Taiwan
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Gannon MR, Dodwell D, Miller K, Horgan K, Clements K, Medina J, Kunkler I, Cromwell DA. Change in the Use of Fractionation in Radiotherapy Used for Early Breast Cancer at the Start of the COVID-19 Pandemic: A Population-Based Cohort Study of Older Women in England and Wales. Clin Oncol (R Coll Radiol) 2022; 34:e400-e409. [PMID: 35691761 PMCID: PMC9151525 DOI: 10.1016/j.clon.2022.05.019] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2022] [Revised: 04/28/2022] [Accepted: 05/25/2022] [Indexed: 11/19/2022]
Abstract
Aims Adjuvant radiotherapy is recommended for most patients with early breast cancer (EBC) receiving breast-conserving surgery and those at moderate/high risk of recurrence treated by mastectomy. During the first wave of COVID-19 in England and Wales, there was rapid dissemination of randomised controlled trial-based evidence showing non-inferiority for five-fraction ultra-hypofractionated radiotherapy (HFRT) regimens compared with standard moderate-HFRT, with guidance recommending the use of five-fraction HFRT for eligible patients. We evaluated the uptake of this recommendation in clinical practice as part of the National Audit of Breast Cancer in Older Patients (NABCOP). Materials and methods Women aged ≥50 years who underwent surgery for EBC from January 2019 to July 2020 were identified from the Rapid Cancer Registration Dataset for England and from Wales Cancer Network data. Radiotherapy details were from linked national Radiotherapy Datasets. Multivariate mixed-effects logistic regression models were used to assess characteristics influential in the use of ultra-HFRT. Results Among 35 561 women having surgery for EBC, 71% received postoperative radiotherapy. Receipt of 26 Gy in five fractions (26Gy5F) increased from <1% in February 2020 to 70% in April 2020. Regional variation in the use of 26Gy5F during April to July 2020 was similar by age, ranging from 49 to 87% among women aged ≥70 years. Use of 26Gy5F was characterised by no known nodal involvement, no comorbidities and initial breast-conserving surgery. Of those patients receiving radiotherapy to the breast/chest wall, 85% had 26Gy5F; 23% had 26Gy5F if radiotherapy included regional nodes. Among 5139 women receiving postoperative radiotherapy from April to July 2020, nodal involvement, overall stage, type of surgery, time from diagnosis to start of radiotherapy were independently associated with fractionation choice. Conclusions There was a striking increase in the use of 26Gy5F dose fractionation regimens for EBC, among women aged ≥50 years, within a month of guidance published at the start of the COVID-19 pandemic in England and Wales.
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Affiliation(s)
- M R Gannon
- Department of Health Services Research & Policy, London School of Hygiene & Tropical Medicine, London, UK; Clinical Effectiveness Unit, The Royal College of Surgeons of England, London, UK.
| | - D Dodwell
- Nuffield Department of Population Health, University of Oxford, Oxford, UK
| | - K Miller
- Department of Health Services Research & Policy, London School of Hygiene & Tropical Medicine, London, UK; Clinical Effectiveness Unit, The Royal College of Surgeons of England, London, UK
| | - K Horgan
- Department of Breast Surgery, St James's University Hospital, Leeds, UK
| | - K Clements
- National Cancer Registration and Analysis Service, NHS Digital, Birmingham, UK
| | - J Medina
- Clinical Effectiveness Unit, The Royal College of Surgeons of England, London, UK
| | - I Kunkler
- University of Edinburgh, Edinburgh, UK
| | - D A Cromwell
- Department of Health Services Research & Policy, London School of Hygiene & Tropical Medicine, London, UK; Clinical Effectiveness Unit, The Royal College of Surgeons of England, London, UK
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Lertbutsayanukul C, Pitak M, Nantavithya C. Long-term oncological outcomes of hypofractionated versus conventional fractionated whole breast irradiation with simultaneous integrated boost in early-stage breast cancer. Radiat Oncol J 2022; 40:141-150. [PMID: 35796117 PMCID: PMC9262705 DOI: 10.3857/roj.2021.00927] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2021] [Accepted: 03/25/2022] [Indexed: 11/18/2022] Open
Abstract
Purpose For patients with early breast cancer who undergo breast-conserving surgery, adjuvant whole breast irradiation (WBI) with simultaneous integrated boost (SIB) results in lower radiotherapy fractions. Published studies have shown that both conventional fraction with SIB (C-SIB) and hypofractionation with SIB (H-SIB) seem to be safe and feasible. In this study, we sought to compare the oncologic outcomes between C-SIB and H-SIB in early-stage breast cancer. Materials and Methods Stage I–II breast cancer patients who received adjuvant WBI with SIB between January 2008 and December 2017 were retrospectively reviewed. The radiation dose in the C-SIB group was 50 Gy and 65 Gy in 25 daily fractions, while in the H-SIB group, it was 43.2 Gy and 52.8 Gy in 16 daily fractions to the whole breast and tumor bed, respectively. Results A total of 188 patients, 103 in the C-SIB group and 85 in the H-SIB group, were included. With a median follow-up time of 87 months, 7-year locoregional control of C-SIB was comparable to H-SIB (95.8% vs. 97.4%, p = 0.964). The 7-year distant metastasis-free survival rates of C-SIB and H-SIB were 89.9% and 95.9% (p = 0.111), while the 7-year disease-free survival rates were 84.2% and 95.4%, respectively (p = 0.176). In multivariate analysis, there was no significant prognostic factor associated with better overall survival. Conclusion H-SIB provided comparable locoregional control to C-SIB. With the advantage of a shorter radiotherapy course, H-SIB could be a favorable option for WBI in early-stage breast cancer.
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Affiliation(s)
- Chawalit Lertbutsayanukul
- Division of Radiation Oncology, Department of Radiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
- Division of Radiation Oncology, Department of Radiology, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
| | - Manida Pitak
- Division of Radiation Oncology, Department of Radiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
- Division of Radiation Oncology, Department of Radiology, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
| | - Chonnipa Nantavithya
- Division of Radiation Oncology, Department of Radiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
- Division of Radiation Oncology, Department of Radiology, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
- Correspondence: Chonnipa Nantavithya Division of Radiation Oncology, Department of Radiology, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, 1873, Rama 4 Rd., Bangkok 10330, Thailand. Tel: +66-2564334 E-mail:
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Sarria GR, Welzel G, Polednik M, Wenz F, Abo-Madyan Y. Prospective Comparison of Hypofractionated Versus Normofractionated Intensity-Modulated Radiotherapy in Breast Cancer: Late Toxicity Results of the Non-Inferiority KOSIMA Trial (ARO2010-3). Front Oncol 2022; 12:824891. [PMID: 35600361 PMCID: PMC9117716 DOI: 10.3389/fonc.2022.824891] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2021] [Accepted: 04/07/2022] [Indexed: 12/24/2022] Open
Abstract
Purpose To compare the late toxicity profile of hypofractionation and normofractionation for whole-breast radiotherapy in breast cancer (BC) patients after conserving surgery. Methods Sixty-year-old or older patients with pTis-pT3, pN0-pN1a, M0 BC were recruited and stratified to hypofractionated (arm R-HF) or normofractionated (arm L-NF) intensity-modulated radiotherapy (IMRT), for right- and left-sided BC, respectively, in this single-center, non-randomized, non-inferiority trial. A boost was allowed if indicated. The primary outcome was the cumulative percentage of patients developing grade III fibrosis, grade I telangiectasia, and/or grade II hyperpigmentation after 2 years, with a pre-specified non-inferiority margin of 15% increase from an expected 2-year toxicity rate of 20%. Results The Median follow-up was 4.93 (0.57-8.65) years for R-HF and 5.02 (0.65-8.72) years for L-NF (p=0.236). The median age was 68 (60-83 and 60-80) years, respectively. In total, 226 patients were recruited (107 for R-HF and 119 for L-NF), with 100 and 117 patients suitable for assessment, respectively. A boost was delivered in 51% and 53% of each arm, respectively. Median PTV volumes were 1013.6 (273-2805) cm3 (R-HF) and 1058.28 (315-2709) cm3 (L-NF, p=0.591). The 2-year primary endpoint rate was 6.1% (95% CI 1.3-11.7, n=5 of 82) and 13.3% (95% CI 7-20.2, n=14 of 105), respectively (absolute difference -7.2%, one-sided 95% CI ∞ to -0.26, favoring R-HF). No local recurrence-free- or overall-survival differences were found. Conclusion In this prospective non-randomized study, hypofractionation did not have higher toxicity than normofractionated whole-breast IMRT.
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Affiliation(s)
- Gustavo R. Sarria
- Department of Radiation Oncology, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
- Department of Radiation Oncology, University Medical Hospital Bonn, University of Bonn, Bonn, Germany
| | - Grit Welzel
- Department of Radiation Oncology, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Martin Polednik
- Department of Radiation Oncology, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Frederik Wenz
- University Medical Center Freiburg, Medical Faculty Freiburg, Freiburg University, Freiburg, Germany
| | - Yasser Abo-Madyan
- Department of Radiation Oncology, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
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Bogers S, Petoukhova A, Penninkhof J, Mast M, Poortmans P, Hoogeman M, Struikmans H. Target Volume Coverage and Organ at Risk Doses for Left-sided Whole-breast Irradiation With or Without Internal Mammary Chain Irradiation: A Comparison Between Three Techniques Representing the Past and the Present. Clin Oncol (R Coll Radiol) 2022; 34:537-544. [DOI: 10.1016/j.clon.2022.04.004] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2021] [Revised: 02/24/2022] [Accepted: 04/06/2022] [Indexed: 11/03/2022]
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Kunkler I. The Evolving Role of Whole Breast Hypofractionation in Older Patients With Early Breast Cancer. Semin Radiat Oncol 2022; 32:155-158. [DOI: 10.1016/j.semradonc.2021.11.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
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Intra-Operative Electron Radiation Therapy (IOERT) Anticipated Boost in Breast Cancer Treatment: An Italian Multicenter Experience. Cancers (Basel) 2022; 14:cancers14020292. [PMID: 35053456 PMCID: PMC8773983 DOI: 10.3390/cancers14020292] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2021] [Revised: 01/04/2022] [Accepted: 01/05/2022] [Indexed: 11/17/2022] Open
Abstract
In breast cancer, the use of a boost to the tumor bed can improve local control. The aim of this research is to evaluate the safety and efficacy of the boost with intra-operative electron radiotherapy (IOERT) in patients with early-stage breast cancer undergoing conservative surgery and postoperative whole breast irradiation (WBI). The present retrospective multicenter large data were collected between January 2011 and March 2018 in 8 Italian Radiation Oncology Departments. Acute and late toxicity, objective (obj) and subjective (subj) cosmetic outcomes, in-field local control (LC), out-field LC, disease-free survival (DFS) and overall survival (OS) were evaluated. Overall, 797 patients were enrolled. IOERT-boost was performed in all patients during surgery, followed by WBI. Acute toxicity (≥G2) occurred in 179 patients (22.46%); one patient developed surgical wound infection (G3). No patients reported late toxicity ≥ G2. Obj-cosmetic result was excellent in 45%, good in 35%, fair in 20% and poor in 0% of cases. Subj-cosmetic result was excellent in 10%, good in 20%, fair in 69% and poor in 0.3% of cases. Median follow-up was 57 months (range 12-109 months). At 5 years, in-field LC was 99.2% (95% CI: 98-99.7); out-field LC 98.9% (95% CI: 97.4-99.6); DFS 96.2% (95% CI: 94.2-97.6); OS 98.6% (95% CI: 97.2-99.3). In conclusion, IOERT-boost appears to be safe, providing excellent local control for early-stage breast cancer. The safety and long-term efficacy should encourage use of this treatment, with the potential to reduce local recurrence.
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Fastner G, Krug D, Meattini I, Gruber G, Poortmans P. Expert Discussion: Hypofractionated Radiation Therapy - Standard for All Indications? Breast Care (Basel) 2021; 17:224-231. [PMID: 35707177 PMCID: PMC9149542 DOI: 10.1159/000521552] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Accepted: 12/16/2021] [Indexed: 11/19/2022] Open
Affiliation(s)
- Gerd Fastner
- Department of Radiotherapy and Radio-Oncology, Paracelsus Medical University, University Hospital Salzburg, Landeskrankenhaus Salzburg, Salzburg, Austria
- *Gerd Fastner,
| | - David Krug
- Department of Radiation Oncology, University Hospital Schleswig Holstein, Kiel, Germany
| | - Icro Meattini
- Department of Experimental and Clinical Biomedical Sciences ”M. Serio”, University of Florence, Florence, Italy
- Radiation Oncology Unit, Oncology Department, Azienda Ospedaliero Universitaria Careggi, Florence, Italy
| | - Günther Gruber
- Institute of Radiotherapy, Klinik Hirslanden, Zurich, Switzerland
- University of Berne, Berne, Switzerland
| | - Philip Poortmans
- Iridium Netwerk, Wilrijk-Antwerp, Belgium
- University of Antwerp, Wilrijk-Antwerp, Belgium
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Vicini F, Broughman J, Halima A, Mayo Z, Obi E, Al-Hilli Z, Arthur D, Wazer D, Shah C. Delivery of Adjuvant Radiation in 5 Days or Less After Lumpectomy for Breast Cancer: A Systematic Review. Int J Radiat Oncol Biol Phys 2021; 112:1090-1104. [PMID: 34921906 DOI: 10.1016/j.ijrobp.2021.11.026] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2021] [Revised: 11/21/2021] [Accepted: 11/29/2021] [Indexed: 10/19/2022]
Abstract
BACKGROUND Recent data have been published supporting the application of ultra-short radiation therapy (RT) regimens for women with early stage breast cancer following breast conserving surgery (BCS). What has remained controversial is whether and how to apply accelerated whole breast irradiation (AWBI) or accelerated partial breast irradiation (APBI) approaches in these patients, as well as the consideration of intraoperative RT (IORT) for this population. METHODS We performed a systematic review of the literature searching for randomized and prospective data published evaluating ultra-short RT delivered in 5-days or less with APBI, AWBI, or IORT. RESULTS We identified two randomized studies applying AWBI (n=5,011 patients) with 5 to 10 year follow up, which supported the use of ultra-short course AWBI (5 fractions in one week) as compared to hypofractionated WBI. We identified six randomized trials evaluating APBI (as compared to WBI) in 5 days or less (n= 8,415) with numerous (n=55) prospective studies as well, with the data supporting short course APBI as compared to WBI. Finally, we identified two randomized trials evaluating IORT; however, both trials demonstrated elevated rates of recurrence with IORT as compared to WBI. CONCLUSIONS The current body of data available for ultra-short adjuvant RT regimens delivered in 5-days or less after BCS overwhelming support their utilization. While data for both exists, APBI regimens have, by far, greater numbers of patients and longer follow-up as compared to AWBI. Also, given increased rates of recurrence seen with IORT with long-term follow-up, this should not be considered a standard approach at this time.
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Affiliation(s)
| | - James Broughman
- Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Ahmed Halima
- Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Zachary Mayo
- Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Elizabeth Obi
- Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Zahraa Al-Hilli
- Department of General Surgery, Digestive Diseases and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Douglas Arthur
- Department of Radiation Oncology, Virginia Commonwealth University, Richmond, VA, USA
| | - David Wazer
- Department of Radiation Oncology, Virginia Commonwealth University, Richmond, VA, USA
| | - Chirag Shah
- Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA.
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Belgioia L, Fozza A, Trapani L, Carmisciano L, Cavagnetto F, Agostinelli S, Guenzi M, Friedman D, Fregatti P, Corvò R. Ten Daily Fractions for Whole Breast Cancer Irradiation: Long Term Results. In Vivo 2021; 35:2875-2880. [PMID: 34410981 PMCID: PMC8408691 DOI: 10.21873/invivo.12576] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2021] [Revised: 06/09/2021] [Accepted: 06/16/2021] [Indexed: 11/10/2022]
Abstract
BACKGROUND/AIM To report the feasibility and oncological outcomes in breast cancer patients treated with a short hypofractionated radiotherapy schedule. PATIENTS AND METHODS We evaluated 380 breast cancer patients treated with ten daily fractions of radiotherapy up to 39 Gy on tumor bed. Primary endpoint was local relapse rate (LRR). Secondary endpoints were overall survival (OS) and metastasis-free survival (MFS). RESULTS The median follow up was 5.0 years. Two- and 5-year LRR rates were 0.2 and 2%, respectively. Two- and 5-year MFS rates were 96.1% and 90.5%, respectively. Two and 5-year OS rates were 97.4% and 95%, respectively. CONCLUSION This short schedule may represent an alternative option to standard mild hypofractionated radiotherapy in breast cancer patients due to its excellent feasibility and very low recurrence rate.
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Affiliation(s)
- Liliana Belgioia
- Department of Health Science (DISSAL), University of Genoa, Genoa, Italy;
- Radiation Oncology Department, IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Alessandra Fozza
- Radiation Oncology Department, IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Luca Trapani
- Department of Health Science (DISSAL), University of Genoa, Genoa, Italy
| | - Luca Carmisciano
- Department of Health Science (DISSAL), Biostatistics Unit, University of Genoa, Genoa, Italy
| | - Francesca Cavagnetto
- Medical Physics Department, IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Stefano Agostinelli
- Medical Physics Department, IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Marina Guenzi
- Radiation Oncology Department, IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Daniele Friedman
- Department of Surgical Science and Integrated Diagnostic (DISC), University of Genoa, Genoa, Italy
- Department of Surgery, IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Piero Fregatti
- Department of Surgical Science and Integrated Diagnostic (DISC), University of Genoa, Genoa, Italy
- Department of Surgery, IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Renzo Corvò
- Department of Health Science (DISSAL), University of Genoa, Genoa, Italy
- Radiation Oncology Department, IRCCS Ospedale Policlinico San Martino, Genoa, Italy
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[Extreme hypofractionation: New indications for breast cancer radiotherapy]. Cancer Radiother 2021; 25:679-683. [PMID: 34452822 DOI: 10.1016/j.canrad.2021.08.004] [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: 07/31/2021] [Accepted: 08/05/2021] [Indexed: 11/21/2022]
Abstract
Due to the continuously increasing number of newly diagnosed breast cancer and limited health resources hypofractionated radiotherapy is a major topic. Recent results from randomized clinical trials assessing extreme hypofractionated radiotherapy for whole or partial breast radiotherapy are practice changing. Here we report toxicity and oncological outcomes from major recent trials of extreme hypofractionated breast irradiation and present an ongoing prospective implementation program. For whole breast irradiation, with a 10 years follow up, the UK-FAST trial demonstrated no significant difference in toxicity between a once weekly 5 fractions (5,7Gy/fr) regimen and a conventional 50Gy/25fr regimen. With a 5 years follow up, the FAST-Forward trial showed non inferiority on local control for a 5 fractions over 1 week (5,2Gy/fr) regimen versus standard 40Gy/15fr over 3 weeks with safe toxicity profile. For accelerated partial breast irradiation, in low-risk breast cancers patients, several phase III randomized trials confirmed that extreme hypofractionation is a valid option. With our "One Week Breast Radiotherapy" program, we propose the implementation of a one-week full workflow preparing and delivering 5 fractions over 1 week (26Gy) in selected patients with prospective follow-up. Several extreme hypofractionated breast radiotherapy regimens are validated and can be routinely discussed with patients in a share decision-making process following patient selection criteria and dosimetric constraints.
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Fehm TN, Stickeler E, Fasching PA, Janni W, Kolberg-Liedtke C, Kolberg HC, Lüftner D, Müller V, Schütz F, Thomssen C, Belleville E, Behrens A, Bader S, Untch M, Welslau M, Würstlein R, Thill M, Krug D, Hartkopf AD. Update Breast Cancer 2021 Part 3 - Current Developments in the Treatment of Early Breast Cancer: Review and Assessment of Specialised Treatment Scenarios by an International Expert Panel. Geburtshilfe Frauenheilkd 2021; 81:654-665. [PMID: 34168379 PMCID: PMC8216783 DOI: 10.1055/a-1487-7642] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2021] [Accepted: 04/20/2021] [Indexed: 12/13/2022] Open
Abstract
The continuous availability of findings from new studies repeatedly results in updated treatment recommendations and guidelines. In the case of breast carcinoma in particular, several studies have been published in the last few years that have transformed how early and advanced breast carcinoma is being treated. However, this by no means means implies that there is agreement among all experts on specific issues. It is precisely the diversity of interpretation of guidelines and study findings that reflects the constantly changing available data and its complexity, as well as the availability of new drugs. In recent years, new substances such as pertuzumab, T-DM1, neratinib and capecitabine have become available to treat patients with early stages of breast carcinoma. Furthermore, the first results on the use of CDK4/6 inhibitors for adjuvant treatment have now been published. Last but not least, the use of multigene tests to avoid the necessity of chemotherapy in certain
patients is still under discussion. This review summarises the state of the data and publishes the results of the survey completed by experts at the 2021 St. Gallen Breast Cancer Conference on early-stage breast cancer.
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Affiliation(s)
- Tanja N Fehm
- Department of Gynecology and Obstetrics, University Hospital Düsseldorf, Düsseldorf, Germany
| | - Elmar Stickeler
- Department of Gynecology and Obstetrics, RWTH University Hospital Aachen, Aachen, Germany
| | - Peter A Fasching
- Erlangen University Hospital, Department of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany
| | - Wolfgang Janni
- Department of Gynecology and Obstetrics, Ulm University Hospital, Ulm, Germany
| | - Cornelia Kolberg-Liedtke
- Department of Gynecology and Obstetrics, University Hospital Essen, Essen, Germany.,palleos healthcare, Wiesbaden, Germany.,Phaon Scientific, Wiesbaden, Germany
| | | | - Diana Lüftner
- Charité University Hospital, Department of Hematology, Oncology and Tumour Immunology, University Medicine Berlin, Berlin, Germany
| | - Volkmar Müller
- Department of Gynecology, Hamburg-Eppendorf University Medical Center, Hamburg, Germany
| | - Florian Schütz
- Gynäkologie und Geburtshilfe, Diakonissen-Stiftungs-Krankenhaus Speyer, Speyer, Germany
| | - Christoph Thomssen
- Department of Gynaecology, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany
| | | | - Annika Behrens
- Erlangen University Hospital, Department of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany
| | - Simon Bader
- Erlangen University Hospital, Department of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany
| | - Michael Untch
- Clinic for Gynecology and Obstetrics, Breast Cancer Center, Genecologic Oncology Center, Helios Klinikum Berlin Buch, Berlin, Germany
| | | | - Rachel Würstlein
- Breast Center, Department of Gynecology and Obstetrics and CCC Munich LMU, LMU University Hospital, Munich, Germany
| | - Marc Thill
- Agaplesion Markus Krankenhaus, Department of Gynecology and Gynecological Oncology, Frankfurt, Germany
| | - David Krug
- Department of Radiation Oncology, University Hospital of Schleswig-Holstein, Kiel, Germany
| | - Andreas D Hartkopf
- Department of Obstetrics and Gynecology, University of Tübingen, Tübingen, Germany
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Untch M, Fasching PA, Brucker SY, Budach W, Denkert C, Haidinger R, Huober J, Jackisch C, Janni W, Kolberg-Liedtke C, Krug D, Kühn T, Loibl S, Lüftner D, Müller V, Schneeweiss A, Thill M, Harbeck N, Thomssen C. Treatment of Patients with Early Breast Cancer: Evidence, Controversies, Consensus: German Expert Opinions on the 17th International St. Gallen Consensus Conference. Geburtshilfe Frauenheilkd 2021; 81:637-653. [PMID: 34168378 PMCID: PMC8216767 DOI: 10.1055/a-1483-2782] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2021] [Accepted: 04/20/2021] [Indexed: 11/10/2022] Open
Abstract
This year's 17th St. Gallen (SG) Consensus Conference on the Treatment of Patients with Early Breast Cancer (SG-BCC) with the title "Customizing local and systemic therapies for women with early breast cancer" focused on the challenge of targeting the treatment of early breast cancer more specifically to the individual disease situation of each patient. As in previous years, a German working group of leading breast cancer experts discussed the results of the international SG-BCC 2021 in the context of the German guideline. It is helpful to compare the SG recommendations with the recently updated treatment recommendations of the Breast Commission of the German Working Group on Gynaecological Oncology (Arbeitsgemeinschaft Gynäkologische Onkologie e. V., AGO) and the S3 guideline because the SG-BCC panel comprised experts from different countries, which is why country-specific aspects can be incorporated into the SG recommendations. The German treatment recommendations of the AGO and the S3 guideline are based on current evidence. Nevertheless, any therapeutic decision must always undergo a risk-benefit analysis for the specific situation and to be discussed with the patient.
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Affiliation(s)
- Michael Untch
- Klinik für Gynäkologie und Geburtshilfe, interdisziplinäres Brustzentrum, HELIOS Klinikum Berlin Buch, Berlin, Germany
| | - Peter A. Fasching
- Frauenklinik des Universitätsklinikums Erlangen, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
| | | | - Wilfried Budach
- Klinik für Strahlentherapie und Radioonkologie, Universitätsklinik Düsseldorf, Düsseldorf, Germany
| | - Carsten Denkert
- Pathologisches Institut, Philipps Universität Marburg und Universitätsklinikum Marburg (UKGM), Marburg, Germany
| | | | - Jens Huober
- Brustzentrum Kantonsspital St. Gallen, St. Gallen, Switzerland
- Brustzentrum, Universitätsfrauenklinik Ulm, Ulm, Germany
| | - Christian Jackisch
- Klinik für Gynäkologie und Geburtshilfe, Sana-Klinikum Offenbach GmbH, Offenbach, Germany
| | | | - Cornelia Kolberg-Liedtke
- Klinik für Frauenheilkunde und Geburtshilfe, Universitätsklinikum Essen, Essen, Germany
- palleos healthcare GmbH, Wiesbaden, Germany
- Phaon scientific GmbH, Wiesbaden, Germany
| | - David Krug
- Klinik für Strahlentherapie (Radioonkologie), Universitätsklinikum Schleswig-Holstein, Campus Kiel, Kiel, Germany
| | - Thorsten Kühn
- Klinik für Frauenheilkunde und Geburtshilfe, Klinikum Esslingen, Esslingen, Germany
| | - Sibylle Loibl
- German Breast Group (GBG), Neu-Isenburg, Germany
- Centrum für Hämatologie und Onkologie Bethanien, Frankfurt am Main, Germany
| | - Diana Lüftner
- Medizinische Klinik mit Schwerpunkt Hämatologie, Onkologie und Tumorimmunologie, Charité Campus Virchow-Klinikum, Berlin, Germany
| | - Volkmar Müller
- Klinik und Poliklinik für Gynäkologie, Universitätsklinik Hamburg-Eppendorf (UKE), Hamburg, Germany
| | - Andreas Schneeweiss
- Sektionsleiter Gynäkologische Onkologie, Nationales Centrum für Tumorerkrankungen (NCT) Universitätsklinikum Heidelberg, Heidelberg, Germany
- Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany
| | - Marc Thill
- Klinik für Gynäkologie und Gynäkologische Onkologie, Interdisziplinäres Brustzentrum, Agaplesion Markus Krankenhaus, Frankfurt am Main, Germany
| | - Nadia Harbeck
- Brustzentrum, Frauenklinik, LMU Klinikum, München, Germany
| | - Christoph Thomssen
- Universitätsklinik und Poliklinik für Gynäkologie, Martin-Luther-Universität Halle-Wittenberg, Halle (Saale), Germany
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