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Stereotactic body radiotherapy for centrally located stage I NSCLC

A multicenter analysis

Stereotaktische Strahlentherapie bei zentralem NSCLC im Stadium I

Eine multizentrische Analyse

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Abstract

Purpose

The purpose of this work is to analyze patterns of care and outcome after stereotactic body radiotherapy (SBRT) for centrally located, early-stage, non-small cell lung cancer (NSCLC) and to address the question of potential risk for increased toxicity in this entity.

Methods and materials

A total of 90 patients with centrally located NSCLC were identified among 613 cases in a database of 13 German and Austrian academic radiotherapy centers. The outcome of centrally located NSCLC was compared to that of cases with peripheral tumor location from the same database.

Results

Patients with central tumors most commonly presented with UICC stage IB (50 %), while the majority of peripheral lesions were stage IA (56 %). Average tumor diameters were 3.3 cm (central) and 2.8 cm (peripheral). Staging PET/CT was available for 73 and 74 % of peripheral and central tumors, respectively. Biopsy was performed in 84 % (peripheral) and 88 % (central) of cases. Doses varied significantly between central and peripheral lesions with a median BED10 of 72 Gy and 84 Gy, respectively (p < 0.001). Fractionation differed as well with medians of 5 (central) and 3 (peripheral) fractions (p < 0.001). In the Kaplan–Meier analysis, 3-year actuarial overall survival was 29 % (central) and 51 % (peripheral; p = 0.004) and freedom from local progression was 52 % (central) and 84 % (peripheral; p < 0.001). Toxicity after treatment of central tumors was low with no grade III/IV and one grade V event. Mortality rates were 0 and 1 % after 30 and 60 days, respectively.

Conclusion

Local tumor control in patients treated with SBRT for centrally located, early-stage NSCLC was favorable, provided ablative radiation doses were prescribed. This was, however, not the case in the majority of patients, possibly due to concerns about treatment-related toxicity. Reported toxicity was low, but prospective trials are needed to resolve the existing uncertainties and to establish safe high-dose regimens for this cohort of patients.

Zusammenfassung

Ziel

Ziel dieser Arbeit war die Analyse von Behandlungsmodalitäten und -ergebnissen nach stereotaktischer Körperstrahlentherapie („stereotactic body radiotherapy“, SBRT) bei zentral gelegenem nichtkleinzelligem Lungenkarzinom („non-small cell lung cancer“, NSCLC). Ebenfalls untersucht wurde, ob im Vergleich zu peripheren Tumoren ein erhöhtes Risiko für posttherapeutische Toxizität besteht.

Methoden und Material

Aus 613 Behandlungsfällen einer Datenbank von 13 hochschulassoziierten Strahlentherapiezentren in Deutschland und Österreich wurden insgesamt 90 Patienten mit zentral gelegenen NSCLC identifiziert. Das Outcome der Patienten mit zentralem NSCLC wurde verglichen mit dem von Patienten aus derselben Datenbank mit peripherer Tumorlokalisation.

Ergebnisse

Die meisten zentralen Tumoren waren Karzinome im UICC-Stadium IB (50 %), die Mehrheit der peripher gelegenen Läsionen dagegen befand sich im Stadium IA (56 %). Die durchschnittlichen Tumordurchmesser betrugen 3,3 cm (zentrale) bzw. 2,8 cm (periphere). Staging-PET/CT-Aufnahmen gab es für 73 bzw. 74 % der peripheren bzw. zentralen Tumoren, Biopsien für 84% (periphere) bzw. 88 % (zentrale). Die Bestrahlungsdosen für zentrale und periphere Läsionen unterschieden sich signifikant voneinander, der BED10-Median lag bei 72 bzw. 84 Gy (p < 0,001). Auch die Fraktionierung war unterschiedlich: die Mediane waren 5 (zentral) und 3 (peripher; p < 0,001) Fraktionen. Nach Kaplan-Meier-Analyse lag das aktuarische Dreijahresüberleben bei 29% (zentral) bzw. 51% (peripher; p =0,004), das lokal progressionsfreie Überleben bei 52% (zentral) bzw. 84% (peripher; p <0,001). Die Toxizität nach der Therapie zentraler Tumoren war gering, es gab kein Grad-III/IV- und nur ein Grad-V-Ereignis. Die 30- bzw. 60-Tage-Mortalitätsraten lagen bei 0 bzw. 1%.

Fazit

Die lokale Kontrolle von zentral gelegenen NSCLC im Frühstadium durch SBRT war akzeptabel − unter der Voraussetzung der Verwendung ablativer Strahlendosen. Dies war bei den meisten Patienten allerdings nicht der Fall, möglicherweise wegen Bedenken über behandlungsbedingte Toxizität. Trotz der milden berichteten Toxizität sind prospektive Studien erforderlich, um die bestehenden Unsicherheiten zu beseitigen und sichere Hochdosisregime für Patienten mit zentralem NSCLC zu etablieren.

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Compliance with ethical guidelines

Conflict of interest

Dr. Andratschke reports grants from the Bavarian State Ministry of the Environment and Public Health during the conduct of the study and payments for lectures by Accuray Inc., Brainlab AG and Merck Serono. D. Schanne, U. Nestle, M. Allgäuer, S. Appold, U. Dieckmann, I. Ernst, U. Ganswindt, A.L. Grosu, R. Holy, M. Molls, M. Nevinny-Stickel, S. Semrau, F. Sterzing, A. Wittig, and M. Guckenberger state that there are no conflicts of interest.

All studies on humans described in the present manuscript were carried out with the approval of the responsible ethics committee and in accordance with national law and the Helsinki Declaration of 1975 (in its current, revised form). Informed consent was obtained from all patients included in studies.

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Authors and Affiliations

  1. Klinik für Strahlenheilkunde, Universitätsklinik Freiburg, Robert-Koch-Str. 3, 79106, Freiburg, Germany

    Daniel H. Schanne M.D., Ursula Nestle M.D., Ph.D. & Anca L. Grosu M.D., Ph.D.

  2. Klinik für Strahlentherapie, Barmherzige Brüder, Regensburg, Germany

    Michael Allgäuer M.D.

  3. Klinik und Poliklinik für Strahlentherapie und Radiologische Onkologie, TU München, München, Germany

    Nicolaus Andratschke M.D., Ph.D. & Michael Molls M.D., Ph.D.

  4. Klinik und Poliklinik für Strahlentherapie und Radioonkologie, Universitätsklinikum Dresden, Dresden, Germany

    Steffen Appold M.D.

  5. Univ. Klinik für Strahlentherapie, Allgemeines Krankenhaus Wien, Wien, Austria

    Ute Dieckmann M.D.

  6. Klinik für Strahlentherapie, Universitätsklinikum Münster, Münster, Germany

    Iris Ernst M.D.

  7. Klinik und Poliklinik für Strahlentherapie und Radioonkologie, LMU München, München, Germany

    Ute Ganswindt M.D.

  8. Klinik für Strahlentherapie, Universitätsklinikum Aachen, Aachen, Germany

    Richard Holy M.D.

  9. Univ. Klinik für Strahlentherapie und Radioonkologie, Medizinischen Universität Innsbruck, Innsbruck, Austria

    Meinhard Nevinny-Stickel M.D., Ph.D.

  10. Strahlenklinik Erlangen, Universitätsklinikum Erlangen, Erlangen, Germany

    Sabine Semrau M.D.

  11. Klinik für Radioonkologie und Strahlentherapie, Universitätsklinikum Heidelberg, Heidelberg, Germany

    Florian Sterzing M.D.

  12. Klinik für Strahlentherapie und Radioonkologie, Philipps-Universität Marburg, Marburg, Germany

    Andrea Wittig M.D., Ph.D.

  13. Klinik und Poliklinik für Strahlentherapie, Universität Würzburg, Würzburg, Germany

    Matthias Guckenberger M.D., Ph.D.

Authors
  1. Daniel H. Schanne M.D.
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  2. Ursula Nestle M.D., Ph.D.
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  3. Michael Allgäuer M.D.
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  4. Nicolaus Andratschke M.D., Ph.D.
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  5. Steffen Appold M.D.
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  6. Ute Dieckmann M.D.
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  7. Iris Ernst M.D.
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  8. Ute Ganswindt M.D.
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  9. Anca L. Grosu M.D., Ph.D.
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  10. Richard Holy M.D.
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  11. Michael Molls M.D., Ph.D.
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  12. Meinhard Nevinny-Stickel M.D., Ph.D.
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  13. Sabine Semrau M.D.
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  14. Florian Sterzing M.D.
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  15. Andrea Wittig M.D., Ph.D.
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  16. Matthias Guckenberger M.D., Ph.D.
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Correspondence to Daniel H. Schanne M.D..

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Schanne, D., Nestle, U., Allgäuer, M. et al. Stereotactic body radiotherapy for centrally located stage I NSCLC. Strahlenther Onkol 191, 125–132 (2015). https://doi.org/10.1007/s00066-014-0739-5

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  • DOI: https://doi.org/10.1007/s00066-014-0739-5

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