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Adjuvant IMRT/XELOX radiochemotherapy improves long-term overall- and disease-free survival in advanced gastric cancer

Adjuvante IMRT/XELOX-Radiochemotherapie verbessert das Gesamt- und krankheitsfreie Überleben beim fortgeschrittenen Magenkarzinom

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Abstract

Purpose

In a retrospective analysis, adjuvant intensity-modulated radiation therapy (IMRT) combined with modern chemotherapy improved advanced gastric cancer survival rates compared to a combination of three-dimensional conformal radiation therapy (3D-CRT) and conventional chemotherapy. We report on the long-term outcomes of two consecutive patient cohorts that were treated with either IMRT and intensive chemotherapy, or 3D-CRT and conventional chemotherapy.

Patients and methods

Between 2001 and 2008, 65 consecutive gastric cancer patients received either 3D-CRT (n = 27) or IMRT (n = 38) following tumor resection. Chemotherapy comprised predominantly 5-fluorouracil/folinic acid (5-FU/FA) in the earlier cohort and capecitabine plus oxaliplatin (XELOX) in the latter. The primary endpoints were overall survival (OS) and disease-free survival (DFS).

Results

Median OS times were 18 and 43 months in the 3D-CRT and IMRT groups, respectively (p = 0.0602). Actuarial 5-year OS rates were 26 and 47  %, respectively. Within the IMRT group, XELOX gave better results than 5-FU/FA in terms of OS, but this difference was not statistically significant. The primary cause of death in both groups was distant metastasis. Median DFS times were 14 and 35 months in the 3D-CRT and IMRT groups, respectively (p = 0.0693). Actuarial 5-year DFS rates were 22 and 44  %, respectively. Among patients receiving 5-FU/FA, DFS tended to be better in the IMRT group, but this was not statistically significant. A similar analysis for the XELOX group was not possible as 3D-CRT was almost never used to treat these patients. No late toxicity exceeding grade 3 or secondary tumors were observed.

Conclusion

After a median follow-up period of over 5 years, OS and DFS were improved in the IMRT/XELOX treated patients compared to the 3D-CRT/5-FU/FA group. Long-term observation revealed no clinical indications of therapy-induced secondary tumors or renal toxicity.

Zusammenfassung

Zielsetzung

In einer retrospektiven Analyse verbesserte die adjuvante Radiochemotherapie mit intensitätsmodulierter Strahlentherapie (IMRT) und moderner Chemotherapie das Überleben von Patienten mit lokal fortgeschrittenem Magenkarzinom gegenüber der Kombination aus 3-dimensionaler konformaler Strahlentherapie (3D-CRT) und konventioneller Chemotherapie. Wir berichten nun über die Langzeitergebnisse von zwei aufeinander folgenden Patientenkohorten, die entweder mit IMRT in Kombination mit einer intensivierten Chemotherapie [Capecitabin/Oxaliplatin (XELOX), spätere Kohorte] oder mit 3D-CRT und konventioneller Chemotherapie [5-Fluorouracil/Folinsäure (5-FU/FA), frühere Kohorte] behandelt worden waren.

Patienten und Methoden

In den Jahren 2001–2008 wurden 65 Patienten konsekutiv wegen eines Magenkarzinoms entweder mit 3D-CRT (n = 27) oder IMRT (n = 38) behandelt. Die Chemotherapie beinhaltete überwiegend 5-FU/FA in der früheren Kohorte und XELOX in der späteren Kohorte. Primäre Endpunkte waren das Gesamtüberleben (OS) und krankheitsfreie Überleben (DFS).

Ergebnisse

Das mediane OS betrug in der 3D-CRT-Gruppe 18 Monate und in der IMRT-Gruppe 43 Monate (p = 0,0602). Das aktuarische 5-Jahres-OS lag nach 3D-CRT bei 26  % und nach IMRT bei 47  %. Innerhalb der IMRT-Gruppe war die intensivierte Chemotherapie der konventionellen hinsichtlich des OS überlegen, der Unterschied erreichte aber keine statistische Signifikanz. Zum Tode führten in beiden Gruppen vorwiegend Fernmetastasen außerhalb des Bestrahlungsfelds. Das mediane DFS betrug 14 Monate in der 3D-CRT-Gruppe und 35 Monate in der IMRT-Gruppe (p = 0,0693). Das aktuarische 5-Jahres-DFS lag bei 22 % in der 3D-CRT und 44 % in der IMRT-Gruppe. Innerhalb der Patientengruppe, die lediglich 5-FU/FA erhalten hatte, zeigte sich ein statistisch nicht signifikanter Vorteil für die IMRT. Eine entsprechende Analyse in der XELOX-Gruppe war nicht möglich, da die Radiotherapie nahezu nie als 3D-CRT durchgeführt worden war. Eine Spättoxizität > Grad 3 und Sekundärtumoren wurden nicht beobachtet.

Schlussfolgerung

Nach einer medianen Beobachtungsdauer von > 5 Jahren war sowohl das OS als auch das DFS in der Patientengruppe mit IMRT/XELOX-Behandlung deutlich verbessert. Die Langzeitbeobachtung erbrachte keine klinischen Hinweise auf Nephrotoxizität oder therapiebedingte Sekundärtumoren.

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Acknowledgements

We thank all referring physicians, Drs. Janka, Hieber, Mühe, Degott, Winter, Schäfer, Kirsch, Slesina, Utz, Massner, Wehrmann, Burkart, Stein, Scholtze, Hornung and Kleiss for providing clinical information and laboratory values. We wish to thank Mrs. Erika Filp and Mrs. Doris Richter for management of archived patient data. Parts of these studies were supported by a research grant from Elekta Inc. and Nomos, as well as from the Federal Ministry of Education and Research (Bundesministerium für Bildung und Forschung, BMBF), Germany. The first author is supported by the Ministry for Education and Research, Baden-Württemberg and the European Social Fonds (ESF).

Conflict of interest

On behalf of all authors, the corresponding author states the following: This work was in part supported by a grant from Elekta Inc. and Nomos. There are no conflicts of interest.

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Authors and Affiliations

  1. Department of Radiation Oncology, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1–3, 68167, Mannheim, Germany

    J. Boda-Heggemann MD, PhD, V. Schneider MSc, H. Wertz, F. Wenz MD & F. Lohr MD

  2. Department of Biomathematics and Medical Statistics, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany

    C. Weiss PhD

  3. III. Department of Internal Medicine, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany

    R.-D. Hofheinz MD

  4. Institute of Diagnostic Radiology and Nuclear Medicine, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany

    S. Haneder MD & H. Michaely MD

  5. Department of Surgery, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany

    U. Ronellenfitsch MD

  6. II. Department of Internal Medicine, University Hospital Jena, Jena, Germany

    A. Hochhaus MD

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  1. J. Boda-Heggemann MD, PhD
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  2. C. Weiss PhD
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  3. V. Schneider MSc
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  4. R.-D. Hofheinz MD
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  5. S. Haneder MD
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  6. H. Michaely MD
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  7. H. Wertz
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  8. U. Ronellenfitsch MD
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  9. A. Hochhaus MD
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  10. F. Wenz MD
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  11. F. Lohr MD
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Corresponding author

Correspondence to J. Boda-Heggemann MD, PhD.

Additional information

J. Boda-Heggemann and C. Weiss contributed equally to this publication.

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Boda-Heggemann, J., Weiss, C., Schneider, V. et al. Adjuvant IMRT/XELOX radiochemotherapy improves long-term overall- and disease-free survival in advanced gastric cancer. Strahlenther Onkol 189, 417–423 (2013). https://doi.org/10.1007/s00066-013-0309-2

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