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Intensity-modulated whole abdomen irradiation following adjuvant carboplatin/taxane chemotherapy for FIGO stage III ovarian cancer

Four-year outcomes

Intensitätsmodulierte Ganzabdomenbestrahlung nach adjuvanter Chemotherapie mit Carboplatin/Taxan beim Ovarialkarzinom im FIGO-Stadium III 4-Jahres-Ergebnisse

Vier-Jahres-Ergebnisse

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Abstract

Introduction

A prospective study to assess toxicity and survival outcomes after intensity-modulated whole-abdominal irradiation (IM-WAI) following surgery and adjuvant intravenous carboplatin/taxane chemotherapy in advanced FIGO stage III ovarian cancer.

Patients and methods

Between 2006 and 2009, 16 patients with optimally resected FIGO stage III ovarian cancer, who had received six cycles of adjuvant carboplatin/taxane chemotherapy were treated with consolidation IM-WAI. Radiotherapy was delivered to a total dose of 30 Gy in 1.5-Gy fractions, using step-and-shoot (n = 3) or helical tomotherapy (n = 13). The first 10 patients were treated within a phase I trial; the following patients received the same treatment modality. The target volume included the entire peritoneal cavity, the diaphragm, the liver capsule, and the pelvic and para-aortic node regions. Organs at risk were kidneys, liver, heart, and bone marrow.

Results

Median follow-up was 44 months (range 19.2–67.2 months). No grade 4 toxicities occurred during IM-WAI. Common Toxicity Criteria for Adverse Events (CTCAE) grade 3 toxicities were: diarrhea (25 %), leucopenia (19 %), nausea/vomiting (6 %), and thrombocytopenia (6 %). No toxicity-related treatment break was necessary. Small bowel obstruction occurred in a total of 6 patients: in 3 cases (19 %) due to postsurgical adhesions and in 3 cases due to local tumor recurrence (19 %). Median recurrence-free survival (RFS) was 27.6 months (95 % confidence interval, CI = 24–44 months) and median overall survival (OS) was 42.1 months (95 %CI = 17–68 months). The peritoneal cavity was the most frequent site of initial failure.

Conclusion

Consolidation IM-WAI following surgery and adjuvant chemotherapy is feasible and can be performed with manageable acute and late toxicity. The favorable RFS outcome is promising and justifies further clinical trials.

Zusammenfassung

Hintergrund

Es wurden Akut- und Langzeittoxizität sowie Überlebensdaten der konsolidierenden intensitätsmodulierten Ganzabdomenbestrahlung („intensity-modulated whole-abdominal irradiation“, IM-WAI) nach adjuvanter Chemotherapie beim Ovarialkarzinom im Stadium FIGO III prospektiv untersucht.

Methoden

Zwischen 2006 und 2009 wurden 16 Patientinnen mit optimal reseziertem Ovarialkarzinom im Stadium FIGO III mittels konsolidierender IM-WAI nach 6 Zyklen adjuvanter Carboplatin-/Taxane-Chemotherapie behandelt. Die ersten 10 Patientinnen wurden im Rahmen einer prospektiven Phase-I-Studie behandelt, danach wurden 6 Patientinnen analog zu dem Studienprotokoll behandelt. Bestrahlt wurde bis zu einer Gesamtdosis von 30 Gy in 1,5 Gy Fraktionen mittels „step-and-shoot“ (n = 3) oder helikaler Tomotherapietechnik (n = 13). Das Zielvolumen umfasste die gesamte Peritonealhöhle, die Zwerchfellkuppeln, die Leberkapsel und die paraaortalen und pelvinen Lymphabflusswege. Risikoorgane waren die Nieren, das Leberparenchym, Herz und Knochen.

Ergebnisse

Das mediane Follow-up betrug 44 Monate (Spanne 19,2–67,2 Monate). Unter Bestrahlung traten keine CTC-Grad-IV-Toxizitäten auf und es fanden keine toxizitätsbedingten Unterbrechungen statt. Beobachtete Grad-III-Akuttoxizitäten waren Diarrhoe (25 %), Leukopenie (19 %), Übelkeit/Erbrechen (6 %) und Thrombozytopenie (6 %). Insgesamt erlitten 6 Patientinnen einen Darmverschluss im späteren Verlauf (37 %). Die Ursachen dafür waren postoperative Briden (19 %) und Peritonealkarzinose (19 %). Das mediane rezidivfreie Überleben (RFS) betrug 27,6 Monate (95 %-KI 24–44 Monate) und das mediane Gesamtüberleben betrug 42,1 Monate (95 %-KI 17–68 Monate). Die Peritonealhöhle war die häufigste Rezidivstelle.

Schlussfolgerung

Die konsolidierende IM-WAI ist machbar und klinisch gut verträglich. Die Daten zum RFS sind vielversprechend und rechtfertigen die Einleitung weiterer klinischer Studien.

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Acknowledgments

The authors would like to thank Karen Lossner and Renate Haselmann for the data management, Omid Khalilzadeh for his statistical support and Anthony H Russell for his linguistic support.

Author information

Authors and Affiliations

  1. Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg, Germany

    Nathalie Rochet M.D., Katja Lindel M.D., Sonja Katayama M.D., Kai Schubert, Klaus Herfarth M.D., Wolfgang Harms M.D. & Juergen Debus M.D., Ph.D.

  2. Department of Radiation Oncology, University of Heidelberg, INF 400, Heidelberg, Germany

    Nathalie Rochet M.D., Katja Lindel M.D., Sonja Katayama M.D., Kai Schubert, Klaus Herfarth M.D., Wolfgang Harms M.D. & Juergen Debus M.D., Ph.D.

  3. Nationales Centrum für Tumorerkrankungen (NCT), University of Heidelberg, Heidelberg, Germany

    Andreas Schneeweiss M.D.

  4. Department of Gynecology, University of Heidelberg, Heidelberg, Germany

    Christoph Sohn M.D.

Authors
  1. Nathalie Rochet M.D.
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  2. Katja Lindel M.D.
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  3. Sonja Katayama M.D.
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  4. Kai Schubert
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  5. Klaus Herfarth M.D.
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  6. Andreas Schneeweiss M.D.
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  7. Christoph Sohn M.D.
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  8. Wolfgang Harms M.D.
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  9. Juergen Debus M.D., Ph.D.
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Corresponding author

Correspondence to Katja Lindel M.D..

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Conflict of interest

N. Rochet, K. Lindel, S. Katayama, K. Schubert, K. Herfarth, A. Schneeweiss, C. Sohn, W. Harms, and J. Debus state that there are no conflicts of interest.

All studies on humans described in the present manuscript were carried out with the approval of the responsible ethics committee and in accordance with national law and the Helsinki Declaration of 1975 (in its current, revised form). Informed consent was obtained from all patients included in studies.

Additional information

Nathalie Rochet and Katja Lindel contributed equally to the article.

This manuscript has not been submitted or published elsewhere.

Presented at DEGRO’s 19th annual meeting, May 9th to 12th 2013 in Berlin (oral presentation, abstract no. A-567-0022-00419)

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Rochet, N., Lindel, K., Katayama, S. et al. Intensity-modulated whole abdomen irradiation following adjuvant carboplatin/taxane chemotherapy for FIGO stage III ovarian cancer. Strahlenther Onkol 191, 582–589 (2015). https://doi.org/10.1007/s00066-015-0830-6

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