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Intensity modulated radiotherapy as neoadjuvant chemoradiation for the treatment of patients with locally advanced pancreatic cancer

Outcome analysis and comparison with a 3D-treated patient cohort

Intensitätsmodulierte Radiotherapie als neoadjuvante Radiochemotherapie zur Behandlung von Patienten mit lokal fortgeschrittenem Pankreaskarzinom

Ergebnisanalyse und Vergleich mit einer Patientenkohorte mit 3-D-Strahlentherapie

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Abstract

Background

To evaluate outcome after intensity modulated radiotherapy (IMRT) compared to 3D conformal radiotherapy (3D-RT) as neoadjuvant treatment in patients with locally advanced pancreatic cancer (LAPC).

Materials and methods

In total, 57 patients with LAPC were treated with IMRT and chemotherapy. A median total dose of 45 Gy to the PTV_baseplan and 54 Gy to the PTV_boost in single doses of 1.8 Gy for the PTV_baseplan and median single doses of 2.2 Gy in the PTV_boost were applied. Outcomes were evaluated and compared to a large cohort of patients treated with 3D-RT.

Results

Overall treatment was well tolerated in all patients and IMRT could be completed without interruptions. Median overall survival was 11 months (range 5–37.5 months). Actuarial overall survival at 12 and 24 months was 36 % and 8 %, respectively. A significant impact on overall survival could only be observed for a decrease in CA 19-9 during treatment, patients with less pre-treatment CA 19-9 than the median, as well as weight loss during treatment. Local progression-free survival was 79 % after 6 months, 39 % after 12 months, and 13 % after 24 months. No factors significantly influencing local progression-free survival could be identified. There was no difference in overall and progression-free survival between 3D-RT and IMRT. Secondary resectability was similar in both groups (26 % vs. 28 %). Toxicity was comparable and consisted mainly of hematological toxicity due to chemotherapy.

Conclusion

IMRT leads to a comparable outcome compared to 3D-RT in patients with LAPC. In the future, the improved dose distribution, as well as advances in image-guided radiotherapy (IGRT) techniques, may improve the use of IMRT in local dose escalation strategies to potentially improve outcome.

Zusammenfassung

Hintergrund

Es handelt sich um eine Analyse der Ergebnisse nach intensitätsmodulierter Radiotherapie (IMRT) im Vergleich zur 3-D-konformalen Strahlentherapie (3-D-RT) bei der neoadjuvanten Behandlung von Patienten mit lokal fortgeschrittenem Pankreaskarzinom (LAPC).

Material und Methoden

57 Patienten mit LAPC wurden mittels IMRT und Chemotherapie behandelt. Eine mediane Gesamtdosis von 45 Gy auf das geplante Zielvolumen, PTV_baseplan, und 54 Gy auf das PTV_boost in Einzeldosen von 1,8 Gy für PTV_baseplan und mediane Einzeldosen von 2,2 Gy auf das PTV_boost wurden appliziert. Überleben sowie lokale Kontrolle wurden analysiert und eine vergleichende Analyse mit einer großen Kohorte von Patienten durchgeführt, welche mittels 3-D-RT behandelt wurden.

Ergebnisse

Die Behandlung wurde insgesamt von allen Patienten gut toleriert und konnte ohne Unterbrechungen durchgeführt werden. Das mediane Gesamtüberleben lag bei 11 Monaten (Spannbreite: 5–37,5 Monate). Das aktuarische Gesamtüberleben nach 12 und 24 Monaten lag bei 36 bzw. 8 %. Als signifikanter Einflussfaktor auf das Gesamtüberleben wurden lediglich die Abnahme des CA 19-9 unter Therapie, ein niedrigeres CA 19-9 als der Median vor Therapie sowie der Gewichtsverlust während der Therapie identifiziert. Das lokale progressionsfreie Überleben lag bei 79 % nach 6 Monaten, bei 39 % nach 12 Monaten und bei 13 % nach 24 Monaten. Es konnten keine signifikanten Einflussfaktoren für das lokale progressionsfreie Überleben identifiziert werden. Sowohl das Gesamtüberleben als auch das progressionsfreie Überleben unterschieden sich nicht zwischen der IMRT- und der 3-D-RT-Kohorte. Die sekundäre Resektabilität war in beiden Gruppen vergleichbar (26 vs. 28 %). Die Toxizität war vergleichbar und bestand vorwiegend aus hämatologischen Nebenwirkungen durch die Chemotherapie.

Schlussfolgerung

Die klinischen Ergebnisse nach IMRT bei der Behandlung des LAPC sind vergleichbar mit der 3-D-RT. In Zukunft könnten jedoch eine verbesserte Dosisverteilung sowie Fortschritte in der Bildsteuerung als „image-guided radiotherapy“ (IGRT) den Einsatz der IMRT für Strategien zur Dosiseskalation optimieren.

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Acknowledgement

We thank Sabine Kuhn and her team for excellent patient care.

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, University Hospital of Heidelberg, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany

    S.E. Combs MD, D. Habermehl MD, K. Kessel, I. Brecht & J. Debus MD PhD

  2. Department of Pathology, University Hospital of Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany

    F. Bergmann MD & P. Schirmacher

  3. Department of Surgery, University Hospital of Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany

    J. Werner MD & M.W. Büchler MD

  4. National Center for Tumor Diseases (NCT), Im Neuenheimer Feld 452, 69120, Heidelberg, Germany

    D. Jäger MD

  5. Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center (dkfz), Im Neuenheimer Feld 270, 69120, Heidelberg, Germany

    J. Debus MD PhD

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  1. S.E. Combs MD
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  2. D. Habermehl MD
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  3. K. Kessel
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Correspondence to S.E. Combs MD.

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Combs, S., Habermehl, D., Kessel, K. et al. Intensity modulated radiotherapy as neoadjuvant chemoradiation for the treatment of patients with locally advanced pancreatic cancer. Strahlenther Onkol 189, 738–744 (2013). https://doi.org/10.1007/s00066-013-0391-5

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  • DOI: https://doi.org/10.1007/s00066-013-0391-5

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