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Randomized multicenter phase II trial of prophylactic irradiation of para-aortic lymph nodes in advanced cervical cancer according to tumor hypoxia: Korean Radiation Oncology Group (KROG 07-01) study

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Author(s)
Meesun YoonHyo Kyung LeeEun Young ParkJin Hee KimJong Hoon LeeYoung Seok KimHak Jae KimHunjung KimChong Woo YooSun LeeEun Kyung HongTae Hyun KimTae-Sung KimSang-soo SeoSokbom KangSuk-Joon ChangHye Jin ShinTung Nguyen Thanh UongSemin LeeJoo-Young Kim
Keimyung Author(s)
Kim, Jin Hee
Department
Dept. of Radiation Oncology (방사선종양학)
Journal Title
Int J Cancer
Issued Date
2022
Volume
151
Issue
12
Keyword
CA9extended-field irradiationHIF-1αHIF-2αlocally advanced cervical cancer
Abstract
We conducted a prospective phase II study on whether extended-field irradiation (EFI) confers survival benefits depending on hypoxic markers in locally advanced uterine cervical cancer (LAUCC). RNA-seq was performed to identify immune and hypoxic gene signatures. A total of 288 patients were randomized to either EFI or pelvic radiotherapy (PRT). All patients completed chemoradiotherapy. Overall, significantly higher 5-year para-aortic recurrence free survival (PARFS) rate occurred in EFI (97.6%) than in PRT group (87.2%), with marginal tendency to improve disease-free survival (DFS; 78% vs 70%, P = .066). Subgroup analyses were performed based on carbonic anhydrase 9 (CA9)-only positive, CA9/hypoxia-inducible factor (HIF) double positive and CA9 negative. In the CA9-only positive, EFI successfully increased 5-year PARFS (100% vs 76.4%, P = .010), resulting in significantly improved long-term DFS (85.7% vs 54.7%, P = .023) compared to the PRT, while there was no such benefit of EFI in the CA9/HIFs double positive. RNA-seq analysis identified distinct immunehigh subgroup with negative correlation with hypoxia gene signatures (R = −.37, P < .01), which showed a higher 5-year DFS than the immunelow (P = .032). Hypoxia-related genes were upregulated in the CA9/HIFs double positive compared to CA9 negative (P < .05). Only 17.4% of patients in CA9-negative group showed immunelow signatures, while 40.0% of patients in the double-positive group exhibited immunelow signatures. In conclusion, EFI improved PARFS significantly in all patients, but therapeutic efficacy of EFI in terms of improved DFS was solely observed in CA9-only positive LAUCC, and not in CA9/HIFs double-positive subgroup. RNA-seq analysis suggested that hypoxia-induced immunosuppression may be related to treatment resistance in LAUCC.
Keimyung Author(s)(Kor)
김진희
Publisher
School of Medicine (의과대학)
Type
Article
ISSN
1097-0215
Source
https://onlinelibrary.wiley.com/doi/10.1002/ijc.34190
DOI
10.1002/ijc.34190
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/44445
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Radiation Oncology (방사선종양학)
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