Junfang Yan

Moderately hypofractionated online adaptive radiotherapy (SWIFT-1) in cervical cancer patients: study protocol for a multi-centered, open-label, two-arm, phase III, randomized controlled study

External beam radiotherapy (EBRT) is an essential component of standard treatment for locally advanced cervical cancer. Moderately hypofractionated radiotherapy (MHRT) offers the potential to reduce treatment burden while compromising efficacy. Although various studies have investigated the safety and efficacy of MHRT, high-quality evidence remains inadequate. The lack of integration of modern radiotherapy techniques in many existing studies may lead to an overestimation of MHRT-associated toxicity. This prospective, multi-center, randomized controlled, non-inferiority phase III trial aims to evaluate the non-inferiority of moderately hypofractionated online adaptive radiotherapy (oART) compared to conventional fractionated radiotherapy (CFRT). A total of 440 participants will be enrolled and randomly assigned in a 1:1 ratio to either the MHRT or CFRT group. Both groups will receive concurrent chemoradiotherapy, and a subset of eligible patients will undergo immunotherapy. The prescribed EBRT dose for the MHRT group will be 43.35 Gy in 17 fractions, with a simultaneous integrated boost of 54.4 Gy in 17 fractions to positive lymph nodes. The CFRT group will receive 45 Gy in 25 fractions, with a simultaneous integrated boost of 60 Gy in 25 fractions to positive lymph nodes. The primary endpoint will be 3-year progression-free survival. Secondary endpoints will include the complete response rate, tumor regression following EBRT, overall survival, locoregional progression-free survival, metastasis-free survival, cervical cancer-specific survival, acute and late toxicity, and quality of life. This randomized controlled trial will prospectively investigate whether MHRT is non-inferior to conventional fractionation in terms of efficacy and safety. Furthermore, the trial will evaluate the potential of moderately hypofractionated oART as a clinically viable alternative to CFRT for the treatment of locally advanced cervical cancer. This trial was registered at ClincalTrials.gov (NCT06641635) on October 12, 2024.

A Prospective Single-Arm Study of Daily Online Adaptive Radiation Therapy for Cervical Cancer with Reduced Planning Target Volume Margin: Acute Toxicity and Dosimetric Outcomes

To evaluate acute toxicity and dosimetric outcomes in cervical cancer treated with daily iterative cone beam computed tomography (iCBCT) guided online adaptive radiation therapy (oART) using reduced planning target volume (PTV) margin. From February 2023 to November 2023, 27 patients with stages I to III cervical cancer were prospectively enrolled in this study. All patients received daily iCBCT guided oART (prescribed 50.4 Gy in 28 fractions) with concurrent weekly chemotherapy followed by brachytherapy. A uniform 10-mm margin was used to cover more variable uterus (PTV-U), and 5-mm margin was used for other PTV. The dosimetric results for each oART fraction were recorded. Both clinician- and patient-reported acute toxicities were assessed before treatment, weekly during treatment, 1 month and 3 months after treatment. The average total treatment time was 22 minutes and 54 seconds, and the adapted plan was selected for all fractions. The adapted plans showed superior coverage for the target volume and dosimetric improvement of organs at risk compared with the scheduled plan. Overall, no patient had grade ≥ 4 acute toxicities. Grades 1, 2, and 3 acute gastrointestinal toxicity were 26%, 19%, and 4%, respectively, among which diarrhea was the most common. Only grade 1 acute genitourinary toxicity was observed in 2 cases (7%). The low incidence of acute toxicity was supported by patient-reported outcome data, which showed significant decreases in mean standard scores on function subscales and significant increases on symptom subscales/items following the initiation of oART. Most of these scales returned to baseline average scores by the 1-month follow-up. This prospective study of daily oART in patients with cervical cancer observed dosimetric benefits and a low incidence of acute toxicity, both in clinician- and patient-reported outcome measurements.

Spectral computed tomography in the assessment of metastatic lymph nodes in cervical cancer patients treated with definitive radiotherapy: a single-center, prospective study

Identifying metastatic lymph nodes (LNs) in patients with cervical cancer treated with definitive radiotherapy may inform treatment strategy and determine prognosis, but available methods have limitations, especially in developing regions. Herein, we aimed to evaluate the performance of quantitative parameters in spectral computed tomography (CT) scanning in this context, focusing on its complementary role alongside conventional diagnostic approaches like 18-fluorine-fuorodeoxyglucose positron emission tomography computed tomography (18 F FDG-PET/CT). Patients with cervical cancer, who underwent pretreatment spectral CT simulation scanning and planned radiotherapy, were enrolled in this prospective study. The LNs were categorized as "metastatic" and "non-metastatic", based on a procedure that included 18 F FDG-PET/CT as well as CT, magnetic resonance imaging, Node Reporting and Data System and follow-up results. Iodine concentrations (IC), normalized IC (NIC), effective atom number (effZ), and spectral curve slope (λ

CT-guided hydrogel injection for brachytherapy in cervical cancer: A case report

Rectal toxicity is a significant concern in cervical cancer radiotherapy. Despite advancements in image-guided brachytherapy (IGBT), rectal morbidity remains a challenge. Injectable hydrogel showed promise in creating a space between the vagina and rectum, reducing rectal radiation dose; however, the traditional ultrasound-guided injection revealed some problems, such as the inadequate separation of the upper edge of the cervix, which can be mitigated through adopting CT-guided injection. This case report presents the successful use of computed tomography (CT)-guided hydrogel injection to limit rectal doses and improve treatment outcomes. A forty-year-old female with stage IIIC1r cervical cancer received external-beam radiotherapy and concurrent chemotherapy. Due to the proximity of the tumor to the rectum, a CT-guided hydrogel injection was performed to increase the distance between the cervix and rectum. Post-injection, magnetic resonance imaging (MRI) demonstrated increased distances between the cervix and rectum. Subsequent MRI-based IGBT achieved high clinical target volume doses while limiting rectal doses. During the six-month follow-up, the patient reported only mild adverse effects. CT-guided hydrogel injection offers advantages over ultrasound-guided injection in cervical cancer radiotherapy. The technique allows for better puncture position adjustment, reduced reliance on specialized ultrasound expertise, and shorter puncture distances. This case report highlights the potential of hydrogel injection as a viable method to reduce rectal morbidity and improve treatment outcomes in a broader range of cervical cancer patients. Further studies are warranted to validate these findings and explore its applicability in larger cohorts.

Pelvic target volume inter-fractional motion during radiotherapy for cervical cancer with daily iterative cone beam computed tomography

Abstract Background Tumor regression and organ movements indicate that a large margin is used to ensure target volume coverage during radiotherapy. This study aimed to quantify inter-fractional movements of the uterus and cervix in patients with cervical cancer undergoing radiotherapy and to evaluate the clinical target volume (CTV) coverage. Methods This study analyzed 303 iterative cone beam computed tomography (iCBCT) scans from 15 cervical cancer patients undergoing external beam radiotherapy. CTVs of the uterus (CTV-U) and cervix (CTV-C) contours were delineated based on each iCBCT image. CTV-U encompassed the uterus, while CTV-C included the cervix, vagina, and adjacent parametrial regions. Compared with the planning CTV, the movement of CTV-U and CTV-C in the anterior-posterior, superior-inferior, and lateral directions between iCBCT scans was measured. Uniform expansions were applied to the planning CTV to assess target coverage. Results The motion (mean ± standard deviation) in the CTV-U position was 8.3 ± 4.1 mm in the left, 9.8 ± 4.4 mm in the right, 12.6 ± 4.0 mm in the anterior, 8.8 ± 5.1 mm in the posterior, 5.7 ± 5.4 mm in the superior, and 3.0 ± 3.2 mm in the inferior direction. The mean CTV-C displacement was 7.3 ± 3.2 mm in the left, 8.6 ± 3.8 mm in the right, 9.0 ± 6.1 mm in the anterior, 8.4 ± 3.6 mm in the posterior, 5.0 ± 5.0 mm in the superior, and 3.0 ± 2.5 mm in the inferior direction. Compared with the other tumor (T) stages, CTV-U and CTV-C motion in stage T1 was larger. A uniform CTV planning treatment volume margin of 15 mm failed to encompass the CTV-U and CTV-C in 11.1% and 2.2% of all fractions, respectively. The mean volume change of CTV-U and CTV-C were 150% and 51%, respectively, compared with the planning CTV. Conclusions Movements of the uterine corpus are larger than those of the cervix. The likelihood of missing the CTV is significantly increased due to inter-fractional motion when utilizing traditional planning margins. Early T stage may require larger margins. Personal radiotherapy margining is needed to improve treatment accuracy.

Moderated Hypofractionated Online Adaptive Radiotherapy in Cervical Cancer

The most common external beam radiotherapy fractionation scheme for cervical cancer is 45-50.4 Gy delivered in 25-28 fractions. However, prolonged treatment duration can lead to insufficient availability of medical resources. We hope to assess the safety and efficacy of moderated hypofractionated online adaptive radiotherapy in combination with brachytherapy in patients with cervical cancer in a multicenter study.