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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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dc.contributor.authorYoon, M-
dc.contributor.authorLee, HK-
dc.contributor.authorPark, EY-
dc.contributor.authorKim, JH-
dc.contributor.authorLee, JH-
dc.contributor.authorKim, YS-
dc.contributor.authorKim, HJ-
dc.contributor.authorKim, H-
dc.contributor.authorYoo, CW-
dc.contributor.authorLee, S-
dc.contributor.authorHong, EK-
dc.contributor.authorKim, TH-
dc.contributor.authorKim, TS-
dc.contributor.authorSeo, SS-
dc.contributor.authorKang, S-
dc.contributor.authorChang, SJ-
dc.contributor.authorShin, HJ-
dc.contributor.authorUong, TNT-
dc.contributor.authorLee, S-
dc.contributor.authorKim, JY-
dc.date.accessioned2023-02-27T07:12:39Z-
dc.date.available2023-02-27T07:12:39Z-
dc.date.issued2022-
dc.identifier.issn0020-7136-
dc.identifier.urihttp://repository.ajou.ac.kr/handle/201003/24832-
dc.description.abstractWe 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 immune(high) subgroup with negative correlation with hypoxia gene signatures (R = -.37, P < .01), which showed a higher 5-year DFS than the immune(low) (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 immune(low) signatures, while 40.0% of patients in the double-positive group exhibited immune(low) 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.-
dc.language.isoen-
dc.subject.MESHAntigens, Neoplasm-
dc.subject.MESHCarbonic Anhydrase IX-
dc.subject.MESHFemale-
dc.subject.MESHHumans-
dc.subject.MESHHypoxia-
dc.subject.MESHLymph Nodes-
dc.subject.MESHProspective Studies-
dc.subject.MESHRepublic of Korea-
dc.subject.MESHTumor Hypoxia-
dc.subject.MESHUterine Cervical Neoplasms-
dc.titleRandomized 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-
dc.typeArticle-
dc.identifier.pmid35751421-
dc.subject.keywordCA9-
dc.subject.keywordextended-field irradiation-
dc.subject.keywordHIF-1α-
dc.subject.keywordHIF-2α-
dc.subject.keywordlocally advanced cervical cancer-
dc.contributor.affiliatedAuthorChang, SJ-
dc.type.localJournal Papers-
dc.identifier.doi10.1002/ijc.34190-
dc.citation.titleInternational journal of cancer-
dc.citation.volume151-
dc.citation.number12-
dc.citation.date2022-
dc.citation.startPage2182-
dc.citation.endPage2194-
dc.identifier.bibliographicCitationInternational journal of cancer, 151(12). : 2182-2194, 2022-
dc.embargo.liftdate9999-12-31-
dc.embargo.terms9999-12-31-
dc.identifier.eissn1097-0215-
dc.relation.journalidJ000207136-
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Obstetrics & Gynecology
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