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Combining advanced radiotherapy technologies to maximize safety and tumor control probability in stage III non-small cell lung cancer

Kombination moderner Bestrahlungstechniken zur Maximierung von Sicherheit und Tumorkontrollwahrscheinlichkeit beim nicht-kleinzelligen Bronchialkarzinom im Stadium III

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Abstract

Background

The goal of the current study was to investigate the tumor control probability (TCP) of advanced radiotherapy technologies for stage III non-small cell lung cancer (NSCLC) and to evaluate potential interplay effects between their applications.

Materials and methods

Three-dimensional conformal radiotherapy (3D-CRT) with conventionally fractionated doses of 66 Gy served as reference for 13 patients with stage III NSCLC. Isotoxic dose escalation relative to the corresponding 3D-CRT plans was performed for three technologies and their combinations: intensity-modulated radiotherapy (IMRT), IMRT with a simultaneous integrated boost (IMRT-SIB) of 10% to the gross tumor volume (GTV), and adaptive re-planning twice during the treatment course (ART). All analyses were based on accumulated dose distributions using deformable image registration of CT images, which were acquired weekly during the treatment course.

Results

IMRT reduced the mean lung dose (MLD) by 5.6% ± 3.8% compared to 3D-CRT. ART resulted in lung sparing of 7.9% ± 4.8% and 9.2% ± 3.9% in 3D-CRT and IMRT planning, respectively. IMRT and ART escalated the irradiation dose by 6.6% ± 3.2% and 8.8% ± 6.3%, respectively, which was not statistically different. For the 7 patients with the largest GTVs, IMRT-SIB was superior to IMRT and ART with dose escalation of 11.9% ± 3.7%. The combination of ART, IMRT, and SIB achieved maximum dose escalation in all 13 patients by 17.1% ± 5.4% on average, which increased TCP from 19.9% ± 7.0 to 37.1% ± 10.1%. Adaptive re-planning was required to continuously conform the escalated and hypofractionated SIB doses to the shrinking tumor.

Conclusion

Combining advanced radiotherapy technologies is considered as a safe and effective strategy to maximize local tumor control probability in stage III NSCLC.

Zusammenfassung

Hintergrund

Ziel dieser Planungsstudie waren die Quantifizierung der lokalen Tumorkontrollwahrscheinlichkeit (TCP) beim lokal fortgeschrittenen Bronchialkarzinom (NSCLC) nach Simulation moderner Bestrahlungstechniken sowie die Ermittlung möglicher Wechselwirkungen der Anwendungen.

Material und Methoden

Die 3-D-konformale Strahlentherapie (3-D-CRT) mit einer konventionell fraktionierten Dosis von 66 Gy diente als Referenz für 13 NSCLC-Patienten im Stadium III. Es wurden die Möglichkeiten zur isotoxischen Bestrahlungsintensivierung mittels dreier fortschrittlicher Bestrahlungstechniken und deren Kombinationen untersucht: Intensitätsmodulierte Strahlentherapie (IMRT), IMRT mit simultan integriertem Boost (IMRT-SIB) von 10% zum makroskopisch sichtbaren Tumorvolumen (GTV) und 2-malige adaptive Replanung während der Behandlungsserie (ART). Alle Analysen basieren auf akkumulierter Dosisverteilung indem eine nichtrigide Bildregistrierung wöchentlich wiederholter CT-Aufnahmen durchgeführt wurde.

Ergebnisse

Im Vergleich zur 3-D-CRT reduzierte die IMRT die mittlere Lungendosis (MLD) um 5,6% ± 3,8%. ART verminderte die Lungenbelastung um jeweils 7,9% ± 4,8% bzw. 9,2% ± 3,9% bei 3-D-CRT oder IMRT-Planung. Die IMRT und ART ermöglichten eine Bestrahlungsintensivierung um 6,6% ± 3,2% bzw. 8,8% ± 6,3%. Dieser Unterschied war nicht statistisch signifikant. In der Subgruppe der 7 Patienten mit den größten Tumorvolumina erzielte die IMRT-SIB mit 11,9% ± 3,7% die signifikant höchste Dosiseskalation. Die Kombination von ART, IMRT und SIB war den einzelnen Technologien in allen 13 Patienten überlegen und erlaubte eine Dosissteigerung um 17,1% ± 5,4%, was die TCP von 19,9% ± 7,0% auf 37,1% ± 10,1% verbesserte. Adaptive Replanung war notwendig, um die hypofraktionierte SIB-Dosis auf den kontinuierlich schrumpfenden Tumor zu begrenzen.

Schlussfolgerung

Die Kombination von modernen Bestrahlungstechniken wird als sichere und effektive Strategie angesehen, um die Tumorkontrollwahrscheinlichkeit beim lokal fortgeschrittenen NSCLC zu verbessern.

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Acknowledgments

The support by Professor Michael Brada and the fruitful discussions with him during the Research Fellowship at the Royal Marsden Hospital are highly acknowledged. MG was supported by the grant GU 1170/1-1 of the German Research Foundation. The work was partially supported by the grant 2007.074.2 of the Wilhelm Sander-Stiftung, München, Germany. MP and AK acknowledge funding from CR UK under grant C46/A10588 and NHS funding from the NIHR Biomedical Research Centre. The support for using the research version of the Pinnacle treatment planning software from Philips Radiation Oncology Systems, Fitchburg, WI, USA, is acknowledged.

Conflict of interest

On behalf of all authors, the corresponding author states that there are no conflicts of interest.

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Authors and Affiliations

  1. Department of Radiation Oncology, University Hospital Würzburg, Josef-Schneider-Str. 11, 97080, Würzburg, Germany

    M. Guckenberger MD

  2. Academic Unit of Radiotherapy & Oncology, The Royal Marsden NHS Foundation Trust, Sutton, Surrey, UK

    M. Guckenberger MD

  3. The Institute of Cancer Research and Lung Unit, The Royal Marsden NHS Foundation Trust, Sutton, Surrey, UK

    M. Guckenberger MD

  4. Joint Department of Physics, The Royal Marsden NHS Foundation Trust, Sutton, Surrey, UK

    A. Kavanagh & M. Partridge

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  1. M. Guckenberger MD
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Correspondence to M. Guckenberger MD.

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Guckenberger, M., Kavanagh, A. & Partridge, M. Combining advanced radiotherapy technologies to maximize safety and tumor control probability in stage III non-small cell lung cancer. Strahlenther Onkol 188, 894–900 (2012). https://doi.org/10.1007/s00066-012-0161-9

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