Prophylactic irradiation of para-aortic lymph nodes for patients with locally advanced cervical cancers with and without high CA9 expression (KROG 07-01): A randomized, open-label, multicenter, phase 2 trial.
The efficacy of prophylactic extended-field irradiation (EFI) plus concomitant cisplatin in patients with locally advanced uterine cervical cancer (LAUCC) is unknown, nor is it known whether tumor carbonic anhydrase IX (CA9) expression level, a hypoxia marker, influences survival outcome.



We recruited patients with UCC, FIGO stage IB1 with pelvic lymph node (LN) metastases to IVA with negative para-aortic LN on PET/CT. CA9 expression was examined and patients were randomized to either EFI or pelvic only radiotherapy (PRT) in each CA9 group. The primary outcomes were para-aortic recurrence-free survival (PARFS) and disease-free survival (DFS).



Between 2006 and 2011, 79 patients with CA9-positive and 37 with CA9-negative tumors were enrolled, respectively. The median follow-up period was 69.2months (range 6.8-102.1). For CA9-positive patients, 5-year PARFS was 100% and 81.7% for those receiving EFI and PRT (p=0.007), respectively. DFS was 78.6% for EFI and 71.3% for PRT patients (p=0.353). For CA9-negative patients, 5y PARFS was 100% and 94.1% for EFI and PRT (p=0.317), respectively. DFS was 100% for EFI and 70.7% for PRT (p=0.018).



EFI significantly reduced recurrences in PAN in patients with CA9-positive tumors, but survival outcome was not improved, due to high local recurrence and high distant metastases rates. This study indicates the necessity for new therapeutic strategies for LAUCC patients whose tumors show high CA9 expression.
Department of Radiation Oncology, Dongsan Medical Center, Keimyung University School of Medicine, Daegu, Republic of Korea.
Jin Hee
JH
Kim
Research Institute and Hospital, National Cancer Center, Goyang, Republic of Korea. Electronic address: jooyoungcasa@ncc.re.kr.
Joo-Young
JY
Kim
Department of Radiation Oncology, Chonnam National University, Hwasun Hospital, Republic of Korea.
Mee Sun
MS
Yoon
Department of Radiation Oncology, Asan Medical Center, Unviersity of Ulsan, College of Medicine, Seoul, Republic of Korea.
Young Seok
YS
Kim
Department of Radiation Oncology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University, Republic of Korea.
Jong Hoon
JH
Lee
Department of Radiation Oncology, Seoul National University, College of Medicine, Republic of Korea.
Hak Jae
HJ
Kim
Department of Radiation Oncology, Inha University Hospital, Inha University, School of Medicine, Incheon, Republic of Korea.
Hunjung
H
Kim
Research Institute and Hospital, National Cancer Center, Goyang, Republic of Korea.
Yeon-Joo
YJ
Kim
Research Institute and Hospital, National Cancer Center, Goyang, Republic of Korea.
Chong Woo
CW
Yoo
Cancer Control and Policy Department, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Republic of Korea.
Byung-Ho
BH
Nam
Research Institute and Hospital, National Cancer Center, Goyang, Republic of Korea.
Tae Hyun
TH
Kim
Research Institute and Hospital, National Cancer Center, Goyang, Republic of Korea.
Suk-Ki
SK
Kim
Research Institute and Hospital, National Cancer Center, Goyang, Republic of Korea.
Sun Ho
SH
Kim
Research Institute and Hospital, National Cancer Center, Goyang, Republic of Korea.
Seokbom
S
Kang
Research Institute and Hospital, National Cancer Center, Goyang, Republic of Korea.
Sang Soo
SS
Seo
Research Institute and Hospital, National Cancer Center, Goyang, Republic of Korea.
Myong Cheol
MC
Lim
Research Institute and Hospital, National Cancer Center, Goyang, Republic of Korea.
Sang-Yoon
SY
Park
D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000235:genetics*; D001011:Aorta; D000071231:Carbonic Anhydrase IX / Q000235:genetics*; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008198:Lymph Nodes / Q000000981:diagnostic imaging / Q000528:radiation effects*; D008207:Lymphatic Metastasis / Q000000981:diagnostic imaging / Q000532:radiotherapy; D008875:Middle Aged; D010388:Pelvis / Q000473:pathology; D016896:Treatment Outcome; D002583:Uterine Cervical Neoplasms / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology*; D055815:Young Adult
D000951:Antigens, Neoplasm; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX
Carbonic anhydrase IX (CA9); Extended-field irradiation (EFI); Radiotherapy; Uterine cervical cancer