Pittaya Dankulchai

Re-irradiation in oligorecurrence and oligometastatic cervical cancer in modern radiotherapy era

Recurrent cervical cancer remains a therapeutic challenge despite advances in primary treatment. The emerging paradigm of oligorecurrence and oligometastasis has opened avenues for curative-intent local therapies, including re-irradiation. Modern radiotherapy techniques have enabled high-dose delivery with acceptable toxicity. This study aims to assess clinical outcomes and treatment-related toxicities in patients with oligorecurrent or oligometastatic cervical cancer treated with modern re-irradiation techniques. This retrospective study included 20 cervical cancer patients with oligorecurrence or synchronous/metachronous oligometastases (≤ 5 lesions) who underwent at least one course of re-irradiation. Survival outcomes including locoregional recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS) were estimated using Kaplan-Meier analysis. Genitourinary (GU), gastrointestinal (GI), and hematologic toxicities were assessed and graded based on CTCAE version 5.0. The median age was 53 years (range: 33-70), with 75% initially diagnosed at FIGO 2018 stage III. The predominant histologies were squamous cell carcinoma (50%) and adenocarcinoma (45%). Recurrences most commonly involved pelvic (30%) and para-aortic (30%) lymph nodes, with 50% occurring in-field. Stereotactic body radiotherapy (SBRT), volumetric modulated arc therapy (VMAT), and MR-guided adaptive brachytherapy (MR-GABT) were the most commonly used re-irradiation modalities, employed in 95% of patients. Median times to first and second recurrence were 11.1 months (IQR: 6.0-17.3) and 13.7 months (IQR: 5.6-21.7), respectively. At a median follow-up of 33.6 months, PFS, LRRFS, DMFS, and OS rates after the first recurrence were were 31.8%, 33.6%, 60.5%, and 84.2% respectively. Grade ≥ 2 genitourinary (GU), gastrointestinal (GI), and hematologic toxicities were observed in 40%, 25%, and 55% of patients, respectively. Grade 3 hematologic toxiciy was 25% and mostly occurred during chemotherapy administration. No grade ≥ 3 GU or GI toxicities were reported. The mean accumulated D0.03 cc after re-irradiation to bladder, rectum, sigmoid and bowel for in-fied/out-of-field were 83.8 ± 6.7/78.5 ± 7.5), 71.2 ± 3.9/69.5 ± 5.2, 68.0 ± 5.5/61.0 ± 5.3, and 62.9 ± 4.6/62.4 ± 7.1 GyEQD2 Re-irradiation with contemporary radiotherapy techniques appears to be a feasible and effective salvage option for selected patients with limited recurrent or metastatic cervical cancer, yielding favorable survival and acceptable toxicity profiles.

Early Results of Hypofractionated Chemoradiation in Cervical Cancer with 44 Gy/ 20 F vs 45 Gy/ 25 F: A Phase II, Open-Label, Randomised Controlled Trial (HYPOCx-iRex Trial)

To compare the safety and efficacy of hypofractionated chemoradiation (HYPO) regimen with a conventional fractionation (CVRT) for locally advanced cervical cancer (LACC). A single-centre, open-label, randomised controlled trial enrolled patients with LACC to receive either HYPO (44 Gy/20 fractions) or CVRT (45 Gy/25 fractions) with intensity-modulated radiotherapy, image-guided adaptive brachytherapy, and concurrent weekly cisplatin. The primary outcome was the incidence of acute and late gastrointestinal (GI) and genitourinary (GU) toxicity assessed using the Common Terminology Criteria for Adverse Events version 5.0. Secondary outcomes included health-related quality of life (HRQoL), disease control, and survival. Forty patients with a median follow-up of 19 months were enrolled (HYPO: n=21; CVRT: n=19). The HYPO achieved a significantly shorter overall treatment time (OTT) compared with CVRT (39 vs 47 days, P < .001). GI and GU toxicities were manageable, with a trend towards higher rates in the HYPO compared with CVRT for both acute (grading [Gr]≥3 CTCAE/patient-reported outcome 43%/29% vs 32%/11%, P=.53/0.24) and actuarial 18-month late GI toxicity (Gr≥2/Gr≥3 26.2%/21.2% vs 20.6%/14.4%, P=.537/0.438), although not statistically significant. No Gr≥3 GU toxicity was observed. HRQoL scores during treatment were lower in the HYPO compared with CVRT; however, recovering within the 3-month post-radiotherapy period. A trend toward superior locoregional control was observed in the HYPO. Notably, para-aortic control at 24 months was significantly higher in the HYPO (100% vs 71.2%, P=.003). No significant differences were observed in local control or overall survival at the time of analysis. HYPO with modern techniques is feasible for LACC, significantly reducing OTT. A trend towards higher yet tolerable acute and late GI toxicity warrants further investigation. Encouragingly, HYPO showed promising locoregional control. thaiclinicaltrials.org (TCTR20210812003).