Adjuvant intensity modulated whole-abdominal radiation therapy for high-risk patients with ovarian cancer FIGO stage III: final results of a prospective phase 2 study

Nathalie Arians, Meinhard Kieser, Laura Benner, Nathalie Rochet, Lars Schröder, Sonja Katayama, Klaus Herfarth, Kai Schubert, Andreas Schneeweiss, Christof Sohn, Katja Lindel, Jürgen Debus, Nathalie Arians, Meinhard Kieser, Laura Benner, Nathalie Rochet, Lars Schröder, Sonja Katayama, Klaus Herfarth, Kai Schubert, Andreas Schneeweiss, Christof Sohn, Katja Lindel, Jürgen Debus

Abstract

Background: To assess late toxicity, quality of life and oncological outcome after consolidative whole abdominal radiotherapy (WART) following cytoreductive surgery and carboplatin/paclitaxel chemotherapy in high risk patients with advanced ovarian cancer FIGO stage III using IMRT (Intensity modulated radiation therapy).

Methods: The OVAR-IMRT-02 study is a multi-center single-arm phase-II-trial. Twenty patients with optimally debulked ovarian cancer stage FIGO III with complete remission after chemotherapy were treated with intensity modulated WART. A total dose of 30 Gy in 20 fractions was applied to the entire peritoneal cavity. Primary endpoint was treatment tolerability; secondary objectives were acute and chronic toxicities, quality of life, rates of therapy disruption/abortion, progression-free survival (PFS) and overall survival (OS).

Results: All patients completed treatment and 10/20 patients (50%) reached the final study follow-up of 36 months. Late side effects consisted of °1-°2 lower limb edema (44.5%), with one patient (5.6%) showing °3 edema. Three patients (16.7%) showed elevated gamma-Glutamyltransferase. There were no severe late side effects regarding renal or hepatic function or any gastrointestinal toxicity greater than °2. During WART, mean global health status decreased by 18.1 points (95%-CI: 7.1-29.0), but completely normalized after 6 months. The same trend was observed for the function scale scores. Kaplan-Meier-estimated 1-, 2- and 3-year PFS was 74, 51 and 40%, respectively. 1-, 2- and 3-year OS was 89, 83 and 83%, respectively.

Conclusions: Intensity modulated WART after aggressive surgery and carboplatin/paclitaxel chemotherapy is associated with an acceptable risk of acute and late toxicity and minor impact on long-term quality of life. Together with the promising results for PFS and OS, intensity modulated WART could offer a new therapeutic option for consolidation treatment of patients with advanced ovarian cancer.

Trial registration: The study is registered with ClinicalTrials.gov ( NCT01180504 ). Registered 12 August 2010 - retrospectively registered.

Keywords: Consolidation treatment; Oncological outcome; Ovarian cancer; Quality of life; Toxicity; Whole abdominal radiotherapy.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Late toxicities of intensity modulated WART. Incidence of late toxicities according to Common Terminology Criteria for Adverse Events version 3.0. (Maximal Common Terminology Criteria for Adverse Events grade later than 6 weeks after end of WART)
Fig. 2
Fig. 2
Late hematological toxicities of intensity modulated WART. Incidence of late hematologic toxicities according to Common Terminology Criteria for Adverse Events version 3.0. (Maximal Common Terminology Criteria for Adverse Events grade later than 6 weeks after end of WART). Abbreviations: AP = alkaline phosphatase; γGT = gamma-Glutamyltranferase; S-GOT = serum glutamic oxaloacetic transaminase; S-GPT = serum glutamic pyruvic transaminase
Fig. 3
Fig. 3
Analysis of quality of life. Function scale scores and global health status scores at baseline, week 4 during radiation therapy, 6 weeks and month 3, 6, 9, 12, 15, 18, 24, 30 and 36 after radiation therapy
Fig. 4
Fig. 4
Kaplan-Meier-estimated Progression-free Survival (PFS)
Fig. 5
Fig. 5
Kaplan-Meier-estimated Overall Survival (OS)

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