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Limb-sparing management with surgical resection, external-beam and intraoperative electron-beam radiation therapy boost for patients with primary soft tissue sarcoma of the extremity

A multicentric pooled analysis of long-term outcomes

Gliedmaßenschonendes Management mit chirurgischer Resektion, externem und intraoperativem Elektronenbestrahlungsschub für Patienten mit primärem Weichteilsarkom der Extremität

Eine multizentrische gepoolte Analyse von Langzeitergebnissen

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Abstract

Background or purpose

A joint analysis of data from three contributing centres within the intraoperative electron-beam radiation therapy (IOERT) Spanish program was performed to investigate the main contributions of IORT to the multidisciplinary treatment of high-risk extremity soft tissue sarcoma (STS).

Methods and materials

Patients with an histologic diagnosis of primary extremity STS, with absence of distant metastases, undergoing limb-sparing surgery with radical intent, external beam radiotherapy (median dose 45 Gy) and IOERT (median dose 12.5 Gy) were considered eligible for participation in this study.

Results

From 1986–2012, a total of 159 patients were analysed in the study from three Spanish institutions. With a median follow-up time of 53 months (range 4–316 years), 5-year local control (LC) was 82 %. The 5-year IOERT in-field control, disease-free survival (DFS) and overall survival (OS) were 86, 62 and 72 %, respectively. On multivariate analysis, only microscopically involved margin (R1) resection status retained significance in relation to LC (HR 5.20, p < 0.001). With regard to IOERT in-field control, incomplete resection (HR 4.88, p = 0.001) and higher IOERT dose (≥ 12.5 Gy; HR 0.32, p = 0.02) retained a significant association in multivariate analysis.

Conclusion

From this joint analysis emerges the fact that an IOERT dose ≥ 12.5 Gy increases the rate of IOERT in-field control, but DFS remains modest, given the high risk of distant metastases. Intensified local treatment needs to be tested in the context of more efficient concurrent, neo- and adjuvant systemic therapy.

Zusammenfassung

Ziel

Um den therapeutischen Beitrag einer intraoperativen Bestrahlung mit Elektronen (IOERT) als Teil eines multidisziplinären Behandlungskonzepts von Weichteilsarkomen (STS) im Extremitätenbereich mit hohem Risikoprofil evaluieren zu können, wurde anhand des spanischen IOERT-Programms eine gepoolte Datenanalyse von drei teilnehmenden Zentren vorgenommen.

Patienten und Methoden

Eingeschlossen in diese Studie wurden Patienten mit histologisch bestätigtem primären STS der Extremitäten ohne Fernmetastasierung, welche nach radikaler extremitätenerhaltenden Operation eine externe Radiotherapie (mediane Dosis 45 Gy) in Kombination mit einer IOERT (mediane Dosis 12,5 Gy) erhielten.

Ergebnisse

In einem Zeitraum von 1986–2012 wurden insgesamt 159 Patienten ausgewertet. Bei einer medianen Nachbeobachtungszeit von 53 Monaten (Spanne 4–316 Monate) wurde eine Lokalkontrolle (LC) nach 5 Jahren von 82 % errechnet. Die 5-Jahres-Raten der LC innerhalb des IOERT-Felds, das krankheitsfreie Überleben (DFS) und das Gesamtüberleben (OS) lagen entsprechend bei 86, 62 und 72 %. In multivariaten Analysen erwiesen sich lediglich mikroskopisch positive Resektionsränder (R1) als signifikant prädiktiv hinsichtlich der LC (HR 5,20; p < 0,001). Innerhalb des ehemaligen IOERT-Felds zeigte in der multivariaten Analyse neben der inkompletten Resektion (HR 4,88; p = 0,001) auch die höhere IOERT-Dosis ≥ 12,5 Gy (HR 0,32; p = 0,02) einen statistisch signifikanten Einfluss.

Schlussfolgerung

Die Ergebnisse aus dieser multiinstitutionellen Analyse lassen den Schluss zu, dass IOERT-Dosen ≥ 12,5 Gy die lokale Kontrollrate im ehemaligen IOERT-Bestrahlungsfeld erhöhen, bei jedoch insgesamt moderatem DFS aufgrund des hohen Metastasierungsrisikos bei dieser Art der Sarkomerkrankung. Diese Behandlungsoption zur intensivierten Erhöhung der LC sollte mit effizienterer konkomitanter, neo- und adjuvanter Systemtherapie weiter untersucht werden.

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Authors and Affiliations

  1. Department of Oncology, Hospital General Universitario Gregorio Marañón, C/Doctor Esquerdo, 46–28007, Madrid, Spain

    Felipe A. Calvo M.D., Ph.D. & Claudio V. Sole M.D.

  2. School of Medicine, Complutense University, Madrid, Spain

    Felipe A. Calvo M.D., Ph.D. & Claudio V. Sole M.D.

  3. Service of Radiation Oncology, Instituto de Radiomedicina, Santiago, Chile

    Claudio V. Sole M.D.

  4. Service of Radiation Oncology, Hospital Universitario Ramón y Cajal, Madrid, Spain

    Alfredo Polo M.D., Ph.D. & Angel Montero M.D.

  5. Service of Radiation Oncology, Clínica Universidad de Navarra, Pamplona, Spain

    Mauricio Cambeiro M.D., Ph.D.

  6. Service of Radiation Oncology, Hospital General Universitario Gregorio Marañón, Madrid, Spain

    Ana Alvarez M.D.

  7. Service of Orthopedics and Traumatology, Hospital General Universitario Gregorio Marañón, Madrid, Spain

    Miguel Cuervo M.D.

  8. Service of Orthopedics and Traumatology, Clínica Universidad de Navarra, Pamplona, Spain

    Mikel San Julian M.D.

  9. Service of Radiation Oncology, Clínica Universidad de Navarra, Pamplona, Spain

    Rafael Martinez-Monge M.D., Ph.D.

Authors
  1. Felipe A. Calvo M.D., Ph.D.
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  2. Claudio V. Sole M.D.
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  3. Alfredo Polo M.D., Ph.D.
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  4. Mauricio Cambeiro M.D., Ph.D.
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  5. Angel Montero M.D.
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  6. Ana Alvarez M.D.
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  7. Miguel Cuervo M.D.
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  8. Mikel San Julian M.D.
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  9. Rafael Martinez-Monge M.D., Ph.D.
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Correspondence to Claudio V. Sole M.D..

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Calvo, F., Sole, C., Polo, A. et al. Limb-sparing management with surgical resection, external-beam and intraoperative electron-beam radiation therapy boost for patients with primary soft tissue sarcoma of the extremity. Strahlenther Onkol 190, 891–898 (2014). https://doi.org/10.1007/s00066-014-0640-2

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  • DOI: https://doi.org/10.1007/s00066-014-0640-2

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