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Integrated boost IMRT with FET-PET-adapted local dose escalation in glioblastomas

Results of a prospective phase II study

Integrated-Boost-IMRT mit FET-PET-adaptierter lokaler Dosiseskalation beim Glioblastom

Ergebnisse einer prospektiven Phase-II-Studie

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Abstract

Purpose

Dose escalations above 60 Gy based on MRI have not led to prognostic benefits in glioblastoma patients yet. With positron emission tomography (PET) using [18F]fluorethyl-L-tyrosine (FET), tumor coverage can be optimized with the option of regional dose escalation in the area of viable tumor tissue.

Methods and materials

In a prospective phase II study (January 2008 to December 2009), 22 patients (median age 55 years) received radiochemotherapy after surgery. The radiotherapy was performed as an MRI and FET-PET-based integrated-boost intensity-modulated radiotherapy (IMRT). The prescribed dose was 72 and 60 Gy (single dose 2.4 and 2.0 Gy, respectively) for the FET-PET- and MR-based PTV-FET(72 Gy) and PTV-MR(60 Gy). FET-PET and MRI were performed routinely for follow-up. Quality of life and cognitive aspects were recorded by the EORTC-QLQ-C30/QLQ Brain20 and Mini-Mental Status Examination (MMSE), while the therapy-related toxicity was recorded using the CTC3.0 and RTOG scores.

Results

Median overall survival (OS) and disease-free survival (DFS) were 14.8 and 7.8 months, respectively. All local relapses were detected at least partly within the 95% dose volume of PTV-MR(60 Gy). No relevant radiotherapy-related side effects were observed (excepted alopecia). In 2 patients, a pseudoprogression was observed in the MRI. Tumor progression could be excluded by FET-PET and was confirmed in further MRI and FET-PET imaging. No significant changes were observed in MMSE scores and in the EORTC QLQ-C30/QLQ-Brain20 questionnaires.

Conclusion

Our dose escalation concept with a total dose of 72 Gy, based on FET-PET, did not lead to a survival benefit. Acute and late toxicity were not increased, compared with historical controls and published dose–escalation studies.

Zusammenfassung

Ziel

Steigerungen der Strahlendosis über 60 Gy, basierend auf der MRT, führten bisher nicht zu einer Prognoseverbesserung bei Glioblastomen. Die [18F]Fluorethyl-L-Tyrosin (FET)-PET erlaubt eine optimierte Erfassung der Tumorausdehnung, womit die Option einer fokussierten Dosiserhöhung im Bereich viabler Tumorareale verbunden ist.

Material und Methoden

In einer prospektiven Phase-II-Studie (2008–2009) erhielten 22 Glioblastom-Patienten eine Strahlenchemotherapie nach erfolgter Resektion. Die Bestrahlung erfolgte als Integrated-Boost-IMRT (IB-IMRT), basierend auf MRT- und postoperativer FET-PET-Bildgebung. Die Dosisverschreibung betrug 72 bzw. 60 Gy (ED 2,4 bzw. 2,0 Gy) für das FET-PET- bzw. MRT-basierte PTV-FET(72 Gy) bzw. PTV-MRT(60 Gy). Das Follow-Up basierte auf regelmäßigen FET-PET- sowie MRT-Untersuchungen. Lebensqualität und kognitive Aspekte wurden mittels EORTC-QLQ-C30 und QLQ-Brain20 sowie „Mini Mental Status“-Test (MMST) erfasst. Die Toxizitätserfassung erfolgte mittels CTC3.0- bzw. RTOG-Score.

Ergebnisse

Gesamt- und rezidivfreies Überleben lagen bei 14,8 und 7,8 Monaten. Alle lokalen Rezidive lagen zumindest partiell innerhalb der 95%-Isodose des PTV-MRT(60 Gy). Höhergradige strahlentherapiespezifische Nebenwirkungen traten nicht auf. Bei 2 Patienten zeigte sich eine Pseudoprogression im MRT. Ein Tumorprogress wurde mittels FET-PET ausgeschlossen und durch weitere Bildgebung bestätigt.

Hinsichtlich der Lebensqualität und Kognition zeigten sich im zeitlichen Verlauf keine signifikanten Veränderungen.

Schlussfolgerung

Unser Dosiseskalationskonzept mit bis zu 72 Gy, basierend auf der FET-PET, führte nicht zu einer Überlebensverbesserung. Eine Erhöhung der Toxizität oder eine signifikante Verschlechterung der Lebensqualität zeigte sich im Vergleich zur historischen Kontrolle nicht.

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Conflict of interest

The corresponding author states that there are no conflicts of interest.

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Authors and Affiliations

  1. Department of Radiation Oncology, RWTH Aachen University Hospital, Pauwelsstr. 30, 52074, Aachen, Germany

    M.D. Piroth, M. Pinkawa, R. Holy, J. Klotz, S. Schaar & M.J. Eble

  2. Institute of Neuroscience and Medicine, Forschungszentrum Jülich, Jülich, Germany

    G. Stoffels, N. Galldiks, H.H. Coenen & K.J. Langen

  3. Department of Nuclear Medicine, RWTH Aachen University Hospital, Aachen, Germany

    H.J. Kaiser

  4. Department of Neurology, University Hospital Cologne, Cologne, Germany

    N. Galldiks

  5. Jülich-Aachen Research Alliance (JARA) – Section JARA-Brain, Forschungszentrum Jülich, Jülich, Germany

    M.D. Piroth, M. Pinkawa, R. Holy, J. Klotz, S. Schaar, G. Stoffels, H.H. Coenen, K.J. Langen & M.J. Eble

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  1. M.D. Piroth
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  2. M. Pinkawa
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Correspondence to M.D. Piroth.

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Piroth, M., Pinkawa, M., Holy, R. et al. Integrated boost IMRT with FET-PET-adapted local dose escalation in glioblastomas. Strahlenther Onkol 188, 334–339 (2012). https://doi.org/10.1007/s00066-011-0060-5

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  • DOI: https://doi.org/10.1007/s00066-011-0060-5

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