Clinical Trial

. 2025 Dec 4;25(1):1862.

doi: 10.1186/s12885-025-15289-0.

Intraoperative radiotherapy in elderly patients with breast cancer: long-term follow-up results of the prospective phase II trial TARGIT-E

Elena Sperk^{1

2}, Claire Lemanski³, Christian Neumaier^{4

5}, Juliane Lauer^{4

6}, Victor Siefert⁴, Ragna Völker⁷, Christoph Lindner⁸, Peter Niehoff^{9

10}, Agnes Richard Tallet¹¹, Séverine Racadot¹², Adeline Petit¹³, Montserrat Pazos¹⁴, Magali Le-Blanc Onfroy¹⁵, Etienne Martin¹⁶, Christiane Reuter¹⁷, Robert Michael Hermann^{18

19}, Fabian Pohl²⁰, Kay Friedrichs²¹, Florian Würschmidt²², Steffi Pigorsch²³, Hans-Christian Kolberg²⁴, Heiko Graf²⁵, Thomas B Brunner^{26

27}, Wolfram Malter²⁸, Tjoung-Wong Park-Simon²⁹, Cosima Brucker³⁰, Jochen Fleckenstein^{31

32}, Cordula Petersen³³, Benjamin Tuschy³⁴, Eva Ekas Wilken³⁵, Sylvia Büttner³⁶, Marc Sütterlin³⁴, Henrik Flyger^#³⁷, Frederik Wenz^#^{4

38}

Affiliations

¹ Department of Radiation Oncology, Medical Faculty Mannheim, University Medical Center Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany. Elena.Sperk@medma.uni-heidelberg.de.
² Mannheim Cancer Center, Medical Faculty Mannheim, University Medical Center Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany. Elena.Sperk@medma.uni-heidelberg.de.
³ Institut de Recherche en Cancérologie de Montpellier (U1194), Department of Radiation Oncology, Montpellier Cancer Institute (ICM), University of Montpellier - Campus Val d'Aurelle, 208 Avenue Des Apothicaires, 34298, Montpellier, France.
⁴ Department of Radiation Oncology, Medical Faculty Mannheim, University Medical Center Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany.
⁵ Clinical Center Worms, MVZ Strahlentherapie Worms GmbH, Gabriel-Von-Seidl-Str. 81, 67550, Worms, Germany.
⁶ Department of Anaesthesiology, Intensive Care Unit and Emergency Medicine, Hospital Ludwigshafen, Bremserstraße 79, 67063, Ludwigshafen, Germany.
⁷ Brustzentrum City, Alexianer St.-Gertrauden Krankenhaus, Paretzer Str. 12, 10713, Berlin, Germany.
⁸ Agaplesion Diakonieklinikum Hamburg, Hohe Weide 17, 20259, Hamburg, Germany.
⁹ Department of Radiation Oncology, Kliniken Köln, Universität Witten/Herdecke, 51067, Neufelder Str. 34Köln, Germany.
¹⁰ Department of Radiation Oncology, Sana Klinkum Offenbach, Starkenburgring 66, 63069, Offenbach, Germany.
¹¹ Radiotherapy Department, Insitut Paoli Calmettes, 232 Boulevard de Sainte-Marguerite, 13009, Marseille, France.
¹² Radiotherapy Department, Centre Léon Bérard, 28 Rue Laënnec, 69008, Lyon, France.
¹³ Department of Radiation Oncology, Institut Bergonié, 229 Cr de l'Argonne, 33076, Bordeaux, France.
¹⁴ LMU Klinikum, Klinik und Poliklinik für Strahlentherapie und Radioonkologie, Campus Innenstadt, Ziemssenstr. 1 80, 336, München, Germany.
¹⁵ Institut de Cancérologie de l'Ouest (ICO), Boulevard Jacques Monod, 44805, Saint Herblain, France.
¹⁶ Georges-François Leclerc Center, Department of Radiotherapy, 1 Rue du Pr Marion, BP77980, 21079, Dijon, France.
¹⁷ Radiologie Plus, Kantonsspital Frauenfeld, Pfaffenholzstrasse 4, 8501, Frauenfeld, Switzerland.
¹⁸ Center for Radiotherapy and Radiooncology Bremen and Westerstede, An der Hössen 34, 26655, Westerstede, Germany.
¹⁹ Department of Radiotherapy, Hannover Medical School, Carl-Neuberg-Straße 1, 30625, Hannover, Germany.
²⁰ Department for Radiotherapy, Regensburg University Hospital, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Germany.
²¹ Mammazentrum HH am Krankenhaus Jerusalem, Moorkamp 2-6, 20357, Hamburg, Germany.
²² Radiologische Allianz Hamburg, Mörkenstraße 47, Hamburg, 22767, Germany.
²³ Technical University of Munich, School of Medicine and Health, Department of RadioOncology and Radiotherapy, Ismaningerstrasse 22, 1675, München, Germany.
²⁴ Department of Gynecology and Obstetrics, Marienhospital Bottrop, Josef-Albers-Str. 70, 46236, Bottrop, Germany.
²⁵ Südthüringer Brustzentrum am Helios Klinikum Meiningen, Bergstraße 3, 98617, Meiningen, Germany.
²⁶ Department of Radiation Oncology, University Medical Center Magdeburg, Leipziger Str. 44, 39120, Magdeburg, Germany.
²⁷ Medizinische Universität Graz, Auenbruggerplatz 32, 8036, Graz, Austria.
²⁸ University of Cologne, Medical Faculty and University Clinic of Cologne, Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf, Department of Gynecology and Gynecologic Oncology, Kerpener Str. 62, 50937, Köln, Germany.
²⁹ Department of Obstetrics and Gynaecology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
³⁰ University Women's Hospital, Paracelsus Medical University Nuremberg, Prof. Ernst Nathan-Str. 1, 90419, Nürnberg, Germany.
³¹ Department of Radiotherapy and Radiation Oncology, Saarland University Medical Center, Kirrberger Str. 100, 66421, Homburg, Germany.
³² Department of Radiotherapy, Westpfalz-Klinikum Kaiserslautern, Hellmut-Hartert-Str. 1, 67655, Kaiserslautern, Germany.
³³ Department of Radiotherapy and Radiation Oncology, Medical Center Hamburg-Eppendorf, Medical Faculty University of Hamburg, Martinistrasse 52, 20246, Hamburg, Germany.
³⁴ Department of Gynecology and Obstetrics, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany.
³⁵ Department of Oncology Herlev and Gentofte Hospital, University of Copenhagen, Borgmester Ib Juuls Vej 1, 2730, Herlev, Denmark.
³⁶ Department of Medical Statistics, Biomathematics and Information Processing, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany.
³⁷ Department of Breast Surgery, Herlev and Gentofte Hospital, University of Copenhagen, Gentofte Hospitalsvej 3B, 2900, Hellerup, Denmark.
³⁸ Medical Faculty, University of Freiburg, Hugstetter Str. 55, 79106, Freiburg im Breisgau, Germany.

^# Contributed equally.

PMID: 41345599
PMCID: PMC12690916
DOI: 10.1186/s12885-025-15289-0

Clinical Trial

Intraoperative radiotherapy in elderly patients with breast cancer: long-term follow-up results of the prospective phase II trial TARGIT-E

Elena Sperk et al. BMC Cancer. 2025.

. 2025 Dec 4;25(1):1862.

doi: 10.1186/s12885-025-15289-0.

Authors

Affiliations

¹ Department of Radiation Oncology, Medical Faculty Mannheim, University Medical Center Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany. Elena.Sperk@medma.uni-heidelberg.de.
² Mannheim Cancer Center, Medical Faculty Mannheim, University Medical Center Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany. Elena.Sperk@medma.uni-heidelberg.de.
³ Institut de Recherche en Cancérologie de Montpellier (U1194), Department of Radiation Oncology, Montpellier Cancer Institute (ICM), University of Montpellier - Campus Val d'Aurelle, 208 Avenue Des Apothicaires, 34298, Montpellier, France.
⁴ Department of Radiation Oncology, Medical Faculty Mannheim, University Medical Center Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany.
⁵ Clinical Center Worms, MVZ Strahlentherapie Worms GmbH, Gabriel-Von-Seidl-Str. 81, 67550, Worms, Germany.
⁶ Department of Anaesthesiology, Intensive Care Unit and Emergency Medicine, Hospital Ludwigshafen, Bremserstraße 79, 67063, Ludwigshafen, Germany.
⁷ Brustzentrum City, Alexianer St.-Gertrauden Krankenhaus, Paretzer Str. 12, 10713, Berlin, Germany.
⁸ Agaplesion Diakonieklinikum Hamburg, Hohe Weide 17, 20259, Hamburg, Germany.
⁹ Department of Radiation Oncology, Kliniken Köln, Universität Witten/Herdecke, 51067, Neufelder Str. 34Köln, Germany.
¹⁰ Department of Radiation Oncology, Sana Klinkum Offenbach, Starkenburgring 66, 63069, Offenbach, Germany.
¹¹ Radiotherapy Department, Insitut Paoli Calmettes, 232 Boulevard de Sainte-Marguerite, 13009, Marseille, France.
¹² Radiotherapy Department, Centre Léon Bérard, 28 Rue Laënnec, 69008, Lyon, France.
¹³ Department of Radiation Oncology, Institut Bergonié, 229 Cr de l'Argonne, 33076, Bordeaux, France.
¹⁴ LMU Klinikum, Klinik und Poliklinik für Strahlentherapie und Radioonkologie, Campus Innenstadt, Ziemssenstr. 1 80, 336, München, Germany.
¹⁵ Institut de Cancérologie de l'Ouest (ICO), Boulevard Jacques Monod, 44805, Saint Herblain, France.
¹⁶ Georges-François Leclerc Center, Department of Radiotherapy, 1 Rue du Pr Marion, BP77980, 21079, Dijon, France.
¹⁷ Radiologie Plus, Kantonsspital Frauenfeld, Pfaffenholzstrasse 4, 8501, Frauenfeld, Switzerland.
¹⁸ Center for Radiotherapy and Radiooncology Bremen and Westerstede, An der Hössen 34, 26655, Westerstede, Germany.
¹⁹ Department of Radiotherapy, Hannover Medical School, Carl-Neuberg-Straße 1, 30625, Hannover, Germany.
²⁰ Department for Radiotherapy, Regensburg University Hospital, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Germany.
²¹ Mammazentrum HH am Krankenhaus Jerusalem, Moorkamp 2-6, 20357, Hamburg, Germany.
²² Radiologische Allianz Hamburg, Mörkenstraße 47, Hamburg, 22767, Germany.
²³ Technical University of Munich, School of Medicine and Health, Department of RadioOncology and Radiotherapy, Ismaningerstrasse 22, 1675, München, Germany.
²⁴ Department of Gynecology and Obstetrics, Marienhospital Bottrop, Josef-Albers-Str. 70, 46236, Bottrop, Germany.
²⁵ Südthüringer Brustzentrum am Helios Klinikum Meiningen, Bergstraße 3, 98617, Meiningen, Germany.
²⁶ Department of Radiation Oncology, University Medical Center Magdeburg, Leipziger Str. 44, 39120, Magdeburg, Germany.
²⁷ Medizinische Universität Graz, Auenbruggerplatz 32, 8036, Graz, Austria.
²⁸ University of Cologne, Medical Faculty and University Clinic of Cologne, Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf, Department of Gynecology and Gynecologic Oncology, Kerpener Str. 62, 50937, Köln, Germany.
²⁹ Department of Obstetrics and Gynaecology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
³⁰ University Women's Hospital, Paracelsus Medical University Nuremberg, Prof. Ernst Nathan-Str. 1, 90419, Nürnberg, Germany.
³¹ Department of Radiotherapy and Radiation Oncology, Saarland University Medical Center, Kirrberger Str. 100, 66421, Homburg, Germany.
³² Department of Radiotherapy, Westpfalz-Klinikum Kaiserslautern, Hellmut-Hartert-Str. 1, 67655, Kaiserslautern, Germany.
³³ Department of Radiotherapy and Radiation Oncology, Medical Center Hamburg-Eppendorf, Medical Faculty University of Hamburg, Martinistrasse 52, 20246, Hamburg, Germany.
³⁴ Department of Gynecology and Obstetrics, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany.
³⁵ Department of Oncology Herlev and Gentofte Hospital, University of Copenhagen, Borgmester Ib Juuls Vej 1, 2730, Herlev, Denmark.
³⁶ Department of Medical Statistics, Biomathematics and Information Processing, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany.
³⁷ Department of Breast Surgery, Herlev and Gentofte Hospital, University of Copenhagen, Gentofte Hospitalsvej 3B, 2900, Hellerup, Denmark.
³⁸ Medical Faculty, University of Freiburg, Hugstetter Str. 55, 79106, Freiburg im Breisgau, Germany.

^# Contributed equally.

PMID: 41345599
PMCID: PMC12690916
DOI: 10.1186/s12885-025-15289-0

Abstract

Background: Whole-breast radiotherapy (WBRT) after breast-conserving surgery (BCS) in older patients can be challenging due to the increased presence of comorbidities, comedication, the presence of a pacemaker or difficulties in traveling to treatment every day. Challenging times, such as the pandemic, can also lead to RT not being performed despite the indication. Very short treatment regimens are therefor of special interest in this population reducing overall treatment time and radiation exposure. TARGIT-E is a phase II trial investigating intraoperative radiotherapy (IORT) during BCS in elderly patients. We report long-term follow-up results of TARGIT-E.

Methods: Patients with BC (≥ 70 years, cT1-2, cN0, M0) were enrolled at 28 European centers. A single dose of IORT (20 Gy) was given during BCS. Additional postoperative WBRT was applied if risk factors were present in final histopathology. Primary outcome was local recurrence-free rate (RFR) using the Kaplan-Meier-method. Late toxicities were assessed by LENT-SOMA criteria, and cosmetic outcomes were graded using BCCT.core software.

Results: In 591 patients (median follow-up 5.4 years) RFR was 97.6% (CI: 96.1, 99.2) and 97.1% (CI: 95.2, 98.9) after 5 and 7 years. Overall survival was 96.2% (CI: 94.4, 98.1) and 91.8% (CI: 91.5, 92.1) after 5 and 7 years. We observed either no or mild late toxicities after 7 years. The most frequent toxicities were fibrosis (grade II-III: 15.7%), pain (grade II-III: 3.3%), retractions (grade I: 30%), and teleangiectasia (grade I: 8.9%). Chronic higher-grade fibrosis was seen in 10% and chronic pain in 2% after 7 years in patients treated with IORT only. Cosmetic outcomes were excellent or good for most patients.

Conclusions: The high local control rate and overall survival in combination with low occurrence of late toxicities over 7 years demonstrate that targeted intraoperative radiotherapy is a fast, simple and feasible method during breast-conserving surgery for selected elderly patients.

Trial registration: TARGIT E was prospectively registered at ClinicalTrials.gov with the number NCT01299987 (date: 18 February 2011).

Keywords: Accelerated partial breast irradiation (APBI); Breast cancer; Breast-conserving surgery; Cosmetic outcome; Elderly patients; Intraoperative radiotherapy (IORT); TARGIT; Toxicity.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: All patients signed informed consent to participate in the study. The protocol and all amendments were approved by the Ethics Committee II at Heidelberg University, Medical Faculty Mannheim with the number 2009-303Strahl.-MA. The study is also under supervision of the Bundesamt für Strahlenschutz (national authority for radiation protection). We confirm that all experiments were performed in accordance with relevant guidelines and regulations. Consent for publication: Not applicable. Competing interests: E. Sperk, M. Sütterlin and R. M. Hermann received honoraria and travel expenses from Carl Zeiss Meditec. H.-C.Kolberg has received honoraria from Pfizer, Seagen, Novartis, Roche, Genomic Health/Exact Sciences, Amgen, AstraZeneca, Riemser, Carl Zeiss Meditec, TEVA, Theraclion, Janssen-Cilag, GSK, LIV Pharma, Lilly, SurgVision, Onkowissen, Gilead, Daiichi Sankyo, Stemline and MSD, travel support from Carl Zeiss Meditec, LIV Pharma, Novartis, Amgen, Pfizer, Daiichi Sankyo, Gilead, Stemline, Tesaro and owns stock of Theraclion SA.

Figures

**Fig. 1**
Study design/treatment scheme of TARGIT-E. *In German, Switzerland and Denmark; **In France; In case of positive margins, re-resection should be done. BCS: Breast-conserving surgery; EIC: Extensive intraductal component; IORT: Intraoperative radiotherapy; L1: Lymphangio invasion; NST: No special type; pN + : Positive lymph nodes; RNI: Regional nodal irradiation; RT: Radiotherapy; SNE: Sentinel node biopsy; WBRT: Whole-breast radiotherapy

**Fig. 2**
A Local recurrence-free rate (RFR). Only local recurrence was counted as an event in this Kaplan–Meier estimate (per protocol). B Local recurrence-free survival. Local recurrences and death counted as an event, whatever occurs first. FU: Follow-up, SE: Standard error

**Fig. 3**
Occurrence of toxicities over time. Depicted are toxicities with LENT-SOMA grade II–III. For retractions and teleangiectasia, grade I is shown, as only mild toxicities of grade I were reported

**Fig. 4**
Toxicity-free rates of selected late toxicities, analyzed by the Kaplan–Meier method. A Rate of patients without chronic fibrosis grade II or III; B Rate of patients without chronic pain of the breast grade II or III; C Rate of patients without retraction; D Rate of patients without teleangiectasia. IORT: Intraoperative radiotherapy; WBRT: Whole-breast radiotherapy, *not significant

**Fig. 5**
Cosmetic outcomes assessed by BCCT.core over the study period

See this image and copyright information in PMC

References

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1. Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: meta-analysis of individual patient data for 10 801 women in 17 randomised trials. Lancet. 2011;378(9804):1707–16. - PMC - PubMed
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Intraoperative radiotherapy in elderly patients with breast cancer: long-term follow-up results of the prospective phase II trial TARGIT-E

Affiliations

Intraoperative radiotherapy in elderly patients with breast cancer: long-term follow-up results of the prospective phase II trial TARGIT-E

Authors

Affiliations

Abstract

Conflict of interest statement

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References

Publication types

MeSH terms

Associated data

LinkOut - more resources

Full Text Sources

Medical