Abstract
BackgroundTo evaluate the initial experience and clinical utility of first-line adjuvant intensity-modulated whole abdominal radiation therapy (WART) in women with ovarian clear cell cancer (OCCC) referred to an academic center.MethodsProgression-free and overall survival was analyzed in a pragmatic observational cohort study of histologically pure OCCC patients over-expressing HNF-1ß treated between 2013 and end-December 2018. An in-house intensity-modulated WART program was developed from a published pre-clinical model. Radiation dose-volume data was curated to American Association of Physics in Medicine (AAPM) Task Group 263 recommendations. A dedicated database prospectively recorded presenting characteristics and outcomes in a standardized fashion.ResultsFive women with FIGO (2018) stage IA to IIIA2 OCCC were treated with first-line WART. Median age was 58 years (range 47–68 years). At diagnosis CA-125 was elevated in 4 cases (median 56 kU/L: range 18.4–370 kU/L) before primary de-bulking surgery. Severe premorbid endometriosis was documented in 3 patients. At a median follow-up of 77 months (range 16–83 mo.), all patients remain alive and progression-free on clinical, biochemical (CA-125), and 18Fluoro-deoxyglucose (FDG) PET/CT re-evaluation. Late radiation toxicity was significant (G3) in 1 case who required a limited bowel resection and chronic nutritional support at 9 months post-WART; 2 further patients had asymptomatic (G2) osteoporotic fragility fractures of axial skeleton at 12 months post-radiation treated with anti-resorptive agents (denosumab).ConclusionsThe clinical utility of intensity-modulated WART in OCCC over-expressing HNF-1β was suggested in this small observational cohort study. The hypothesis that HNF-1β is a portent of platinum-resistance and an important predictive biomarker in OCCC needs further confirmation. Curating multi-institutional cohort studies utilizing WART by means of “Big Data” may improve OCCC care standards in the future.
Highlights
To evaluate the initial experience and clinical utility of first-line adjuvant intensity-modulated whole abdominal radiation therapy (WART) in women with ovarian clear cell cancer (OCCC) referred to an academic center
We describe for the first time the clinical utility of contemporary intensity-modulated WART in a small prospective series of OCCC patients whose phenotypic signature included Hepatocyte nuclear factor (HNF)-1β over-expression
This study was pre-approved by the Northern Sydney Local Health District (NSLHD) and included patients who had consented to the use of their oncologic and general medical data stored by the Northern Sydney Cancer Center for clinical follow-up and research purposes
Summary
To evaluate the initial experience and clinical utility of first-line adjuvant intensity-modulated whole abdominal radiation therapy (WART) in women with ovarian clear cell cancer (OCCC) referred to an academic center. Ovarian cancer will remain the second leading cause of gynecologic cancer mortality [1,2,3]. Primary cancers of surface-epithelial origin constitute the majority (90%) of ovarian malignancies [4]. These all originate from the primitive Mullerian epithelium, considerable heterogeneity in biologic behavior, genetic stability, therapeutic responsiveness, and mortality risk [5,6,7,8,9,10,11,12] exist within the 4 major epithelial phenotypes: serous, mucinous, endometrioid, and clear cell cancer. Despite the known disparities between these subtypes, current therapeutic algorithms for epithelial ovarian cancer remain largely harmonious with primary or secondary de-bulking surgery followed or preceded (respectively), by platinum/taxane-based chemotherapy
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