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Risk-adapted robotic stereotactic body radiation therapy for inoperable early-stage non-small-cell lung cancer

Risikoadaptierte robotergestützte stereotaktische Strahlentherapie beim inoperablen nicht-kleinzelligen Bronchialkarzinom im Frühstadium

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Abstract

Purpose

To evaluate efficacy and toxicity of stereotactic body radiation therapy (SBRT) with CyberKnife® (Accuray, Sunnyvale, CA, USA) in a selected cohort of primary, medically inoperable early-stage non-small cell lung cancer (NSCLC) patients.

Methods

From 2012 to 2016, 106 patients (median age 74 years, range 50–94 years) with primary NSCLC were treated with SBRT using CyberKnife®. Histologic confirmation was available in 87 patients (82%). For mediastinal staging, 92 patients (87%) underwent 18F-fluorodeoxyglucose positron-emission tomography (18-FDG-PET) and/or endobronchial ultrasound (EBUS)-guided lymph node biopsy or mediastinoscopy. Tumor stage (UICC8, 2017) was IA/B (T1a-c, 1–3 cm) in 86 patients (81%) and IIA (T2a/b, 3–5 cm) in 20 patients (19%). Depending on tumor localization, three different fractionation schedules were used: 3 fractions of 17Gy, 5 fractions of 11Gy, or 8 fractions of 7.5 Gy. Tracking was based on fiducial implants in 13 patients (12%) and on image guidance without markers in 88%.

Results

Median follow-up was 15 months (range 0.5–46 months). Acute side effects were mild (fatigue grade 1–2 in 20% and dyspnea grade 1–2 in 17%). Late effects were observed in 4 patients (4%): 3 patients developed pneumonitis requiring therapy (grade 2) and 1 patient suffered a rib fracture (grade 3). In total, 9/106 patients (8%) experienced a local recurrence, actuarial local control rates were 88% (95% confidence interval, CI, 80–96%) at 2 years and 77% (95%CI 56–98%) at 3 years. The median disease-free survival time was 27 months (95%CI 23–31 months). Overall survival was 77% (95%CI 65–85%) at 2 years and 56% (95%CI 39–73%) at 3 years.

Conclusion

CyberKnife® lung SBRT which allows for real-time tumor tracking and risk-adapted fractionation achieves satisfactory local control and low toxicity rates in inoperable early-stage primary lung cancer patients.

Zusammenfassung

Zielsetzung

Untersuchung von Wirkung und Toxizität einer stereotaktischen Bestrahlung (SBRT) bei Patienten mit Frühstadien von medizinisch inoperablen primären nichtkleinzelligen Bronchialkarzinomen (NSCLC) am CyberKnife® (Accuray, Sunnyvale, CA, US).

Methoden

Von 2012 bis 2016 wurden 106 Patienten (medianes Alter 74 Jahre, Spanne 50–94 Jahre) mit primärem NSCLC mittels SBRT am CyberKnife® behandelt. Bei 87 Patienten (82 %) war der Tumor histologisch gesichert. Zum Ausschluss mediastinaler Lymphknotenmetastasen erhielten 92 Patienten (87 %) eine 18Fluorodeoxyglukose-Positronenemissionstomographie (18FDG-PET) und/oder einen endobronchialen Ultraschall (EBUS) mit Lymphknotenbiopsie oder eine Mediastinoskopie. Das Tumorstadium (UICC8, 2017) war bei 86 Patienten IA/B (T1a–c, 1–3 cm) und bei 20 (19 %) IIA (T2a/b, 3–5 cm). Abhängig von der Tumorlokalisation wurden drei Fraktionierungsschemata verwendet: 3 × 17 Gy, 5 × 11 Gy, 8 × 7,5 Gy. Für das Tracking wurden 13 Patienten (12 %) Marker-Seeds implantiert, in 88 % erfolgte die Bestrahlung bildgesteuert ohne Marker.

Ergebnisse

Das mediane Follow-up betrug 15 Monate (Spanne 0,5–46 Monate). Akute Nebenwirkungen waren mild (Fatigue Grad 1–2 in 20 %, Atemnot Grad 1–2 in 17 %). Spättoxizitäten zeigten sich bei 4 Patienten (4 %): 3‑mal eine Pneumonitis (Grad 2),1-mal eine Rippenfraktur (Grad 3). Bei 9/106 Patienten (8 %) trat ein Lokalrezidiv auf, die lokale Kontrollrate betrug 88 % (95 %-Konfidenzintervall [KI] 80–96 %) nach 2 und 77 % (95 %-KI 56–98 %) nach 3 Jahren. Das mediane krankheitsfreie Überleben war 27 Monate (95 %-KI 23–31 Monate). Das Gesamtüberleben betrug 77 % (95 %-KI 65–85 %) nach 2 und 56 % (95 %-KI 39–73 %) nach 3 Jahren.

Schlussfolgerung

Durch Tumor-Tracking in Echtzeit und risikoadaptierte Fraktionierung führt die CyberKnife®-SBRT der Lunge bei inoperablen primären NSCLC-Patienten im Frühstadium zu einer guten lokalen Kontrolle bei niedrigen Toxizitätsraten.

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Authors and Affiliations

  1. Department of Radiation Oncology, Center for Integrated Oncology, University of Cologne, Kerpener Str. 62, 50937, Cologne, Germany

    Susanne Temming,  Martin Kocher, Wolfgang W. Baus, Robert Semrau, Christian Baues & S. Marnitz

  2. Lung Clinic Merheim, Hospital of Cologne, Cologne, Germany

    Erich Stoelben

  3. Bethanien Hospital, Institute of Pneumology, University of Cologne, Solingen, Germany

    Lars Hagmeyer

  4. Department of Diagnostic and Interventional Radiology, Center for Integrated Oncology, University of Cologne, Cologne, Germany

    De-Hua Chang

  5. Department III of Internal Medicine, Heart Centre of the University of Cologne, Cologne, Germany

    Konrad Frank

  6. Department of Cardiothoracic Surgery, Center for Integrated Oncology, University of Cologne, Cologne, Germany

    Khosro Hekmat

  7. First Department of Internal Medicine, Center for Integrated Oncology, University Hospital of Cologne, Cologne, Germany

    Juergen Wolf

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  1. Susanne Temming
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  2. Martin Kocher
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Correspondence to Martin Kocher.

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Conflict of interest

S. Temming, M. Kocher, E. Stoelben, L. Hagmeyer, D.-H. Chang, K. Frank, K. Hekmat, J. Wolf, W.W. Baus, R. Semrau, C. Baues, and S. Marnitz declare that they have no competing interests.

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Temming, S., Kocher, M., Stoelben, E. et al. Risk-adapted robotic stereotactic body radiation therapy for inoperable early-stage non-small-cell lung cancer. Strahlenther Onkol 194, 91–97 (2018). https://doi.org/10.1007/s00066-017-1194-x

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