Meesun Yoon

Postoperative conventional versus hypofractionated intensity-modulated radiation therapy with concurrent chemotherapy in cervical cancer: a prospective multicenter randomized phase III trial (POHIM_P3 trial)

For patients with high-risk factors such as pelvic lymph node metastasis, positive surgical margins, or parametrial involvement, concurrent chemoradiotherapy (CCRT) with whole-pelvic radiotherapy significantly improves survival outcomes. Hypofractionated radiation therapy, which delivers higher radiation doses over fewer sessions, enhances tumor control but raises concerns about increased normal tissue toxicity. A recent Korean phase II study (POHIM-CCRT) evaluated the safety of hypofractionated intensity-modulated radiation therapy (IMRT), delivering 40 Gy in 16 fractions with weekly cisplatin following radical surgery. The results showed minimal acute toxicity. Based on these findings, the present study was designed to assess the oncologic efficacy of hypofractionated CCRT compared to conventional treatment strategies in high-risk cervical cancer patients after radical surgery. The POHIM-P3 trial is a phase 3, randomized, multicenter study designed for women with cervical cancer requiring adjuvant CCRT after radical hysterectomy. Participants in the experimental arm receive hypofractionated IMRT to whole pelvis, delivering a total dose of 40 Gy in 16 fractions, and the control arm receive conventional radiotherapy with a total dose of 45-50.4 Gy in 25-28 fractions in combination with weekly cisplatin. The primary endpoint of the study is the 3-year disease-free survival and the secondary endpoints included acute and late side-effects, local control rates, and overall survival rates. ClinicalTrials.gov Identifier: NCT06509724.

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

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 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.

Comparison of Conventional and Hypofractionated IMRT in High-Risk Cervical Cancer Post-Radical Hysterectomy

Radical hysterectomy and radiation therapy are standard treatments for cervical cancer. However, there are no reported studies on the frequency of side effects and treatment outcomes when hypofractionated radiation therapy and intensity modulated radiation therapy(IMRT) are used during radiation therapy. Hypofractionated radiation therapy increases the daily dose and reduces the number of treatment sessions, which may increase the risk of side effects, but its safety has been confirmed in some cases of early cervical cancer and endometrial cancer. Additionally, applying IMRT, a technique designed to protect normal tissue, during concurrent chemoradiotherapy has shown positive results in reducing the incidence of acute side effects. Investigators previously demonstrated that combining hypofractionated IMRT with chemotherapy for high-risk postoperative cervical cancer patients resulted in high survival rates and low toxicity in a phase 2 exploratory study. Base on this result, this study aimed to compare the efficacy and safety of conventional fractionated radiation therapy and hypofractionated radiation therapy.