Junjie Wang

Dosimetric evaluation of different cylinder diameters in three-dimensional vaginal brachytherapy for early-stage endometrial cancer

To evaluate the dosimetric, radiobiological, and toxicity differences between different cylinder diameters (d) in high-dose-rate three-dimensional computed-tomography-guided vaginal brachytherapy (VBT) for early-stage endometrial cancer (EC). From January 2019 to January 2024, postoperative EC patients treated with exclusive VBT using cylinders were classified by the cylinder diameter (d ≤ 2.6 cm: small-size; d ≥ 3.0 cm: large-size) and matched according to 1:2 propensity score matching. Vaginal clinical target volume (CTV) was a 3-mm expansion around the cylinder surface. Dosimetric parameters in equivalent dose in 2 Gy (EQD2) (α/β = 3 Gy) and equivalent uniform dose (EUD) of vaginal_CTV and organs at risk (OARs) were evaluated. Urinary, gastrointestinal, and vaginal toxicities were assessed using CTCAE v5.0. After matching, 132 patients (small-size: 44; large-size: 88) were analyzed. For vaginal_CTV, the small-size group had higher doses to 2%, 5%, 0.1 cc, 1 cc, and 2 cc of the volume (D Cylinders with smaller diameters produced more nonuniform dose distributions in the target and delivered lower doses to bladder and rectum than large-size cylinders. However, the dosimetric differences did not translate into significant differences of radiobiological parameters or outcomes.

Is Moderately Hypofractionated Radiotherapy a Safe and Effective Strategy for Cervical Cancer?—A Review of Current Evidence

Cervical cancer (CC) remains a leading cause of cancer-related mortality, particularly in low- and middle-income countries (LMICs), despite advancements in HPV vaccination and screening. Radiotherapy (RT) plays a critical role in managing CC, but conventional fractionated radiotherapy (CFRT) is limited by long treatment durations, which reduce patient adherence, increase the risk of treatment interruptions, and impair healthcare access in LMICs. Moderately hypofractionated radiotherapy (MHRT) may offer a promising alternative, delivering higher doses per fraction with fewer total fractions, thus shortening treatment duration and alleviating the burden on both patients and healthcare systems. Early clinical data suggest that MHRT achieve acceptable short- to medium-term tumor control with manageable toxicity. However, the small sample sizes and limited follow-up in published studies preclude definitive conclusions about long-term efficacy and safety. This review synthesizes the existing clinical evidence to outline the potential benefits and inherent limitations of MHRT in CC management and highlight the need for future large-scale, long-term randomized controlled trials with rigorous quality assurance protocols. These findings also have implications for the potential implementation of MHRT in LMICs.

A bidirectional Mendelian randomization analysis of the causal relationship between immune cells and high-grade squamous intraepithelial lesion

High-grade squamous intraepithelial lesions (HSIL), critical precursors to cervical cancer, are associated with persistent human papillomavirus infection and immune dysregulation, yet the causal role of specific immune cell phenotypes remains unclear. To investigate bidirectional causal relationships, we performed a 2-sample Mendelian randomization (MR) analysis using European genome-wide association study data: 731 immune cell phenotypes and HSIL. Instrumental variables ( P  < 1 × 10⁻⁵) were selected under MR assumptions, with inverse-variance weighted as the primary method. Forward MR (immune cells to HSIL) identified 67 phenotypes nominally associated ( P  < .05); after FDR correction (FDR < 0.20), IgD on transitional B cells were protective, while increased CD3 on CD39+ Tregs elevated risk. Reverse MR (HSIL to immune cells) indicated HSIL causally reduces naïve CD4− CD8− T cell, HVEM on effector memory CD8+ T cells, FSC-A on lymphocyte and FSC-A on T cells (FDR < 0.20). This study provides genetic evidence for causal roles of specific immune phenotypes in HSIL pathogenesis, suggesting immunotherapeutic targets, while revealing HSIL-induced immune exhaustion patterns.

Efficacy and safety of 3-dimensional printing noncoplanar template (3D-PNCT)-assisted high-dose-rate interstitial brachytherapy (HDR-ISBT) for reirradiation of recurrent cervical cancer: a prospective cohort

This study aimed to investigate the efficacy and safety of 3-dimensional printing noncoplanar template (3D-PNCT)-assisted computed tomography (CT)-guided high-dose-rate interstitial brachytherapy (HDR-ISBT) for reirradiation of pelvic recurrent cervical carcinoma after external beam radiotherapy. From January 2019 to August 2023, 45 eligible patients were enrolled in this prospective cohort. All patients underwent 3D-PNCT-assisted CT-guided HDR-ISBT with a prescribed dose of 4-7 Gy/fraction to the high-risk clinical target volume (HR-CTV) over 3-8 fractions, either for curative or palliative purposes. The primary endpoints were local progression-free survival (LPFS) and tumor response rate (TRR). The secondary outcome measures included overall survival (OS), toxicities, and symptom resolution. Forty-five patients received 261 fractions of 3D-PNCT-assisted HDR-ISBT. Twenty-nine patients had isolated pelvic recurrence, and 16 patients had simultaneous extra-pelvic or distant recurrences. The TRR was 66.7%. The 2- and 5-year LPFS rates were 30.0% and 25.7%, respectively. The median OS was 23.2 months, and 2- and 5-year OS rates were 49.5% and 34.0%, respectively. The multivariate analysis indicated that squamous cell carcinoma, radical surgery, recurrence-free interval≥12 months, tumor diameter, pelvic recurrence type, and HR-CTV D₉₀≥45 Gy were independent factors influencing LPFS (all p<0.05). D₁₀₀≥21 Gy, V₁₀₀≥83%, and V₁₅₀≥45% were associated with better LPFS (all p<0.05). Tumor diameter and metastasis were independent predictive factors for OS (all p<0.05). The pain relief rate was 66.7% (10/15). Grade 3-4 toxicities occurred in 20.0% of patients. 3D-PNCT-assisted HDR-ISBT for reirradiation of recurrent cervical cancer proved to be an effective and safe alternative to radical surgery.

High-Dose-Rate Three-Dimensional Image-Guided Adaptive Brachytherapy (3D IGABT) for Locally Advanced Cervical Cancer (LACC): A Narrative Review on Imaging Modality and Clinical Evidence

Background: Brachytherapy (BT) is a critical component of radiotherapy for locally advanced cervical cancer (LACC), and it has rapidly developed in recent decades. Since the advent of three-dimensional image-guided adaptive brachytherapy (3D-IGABT), magnetic resonance imaging (MRI) has emerged as the primary modality for image guidance. Meanwhile, other imaging modalities, such as computed tomography, 18F-fluorodeoxyglucose positron emission tomography, ultrasound, and their combinations have also been widely studied. Materials and methods: We reviewed studies on different imaging modalities utilized for target delineation and planning. Emerging techniques in IGABT like real-time image guidance and 3D printing were also included. We summarized research on their feasibility and concentrated on their clinical outcomes. Results: MRI-guided BT was the gold standard, and CT-guided BT was the most widely applied. Other modalities have shown feasibility and promising efficacy in dosimetry studies and preliminary outcomes. The longer-term clinical outcomes associated with these approaches require further elucidation. Conclusions: As 3D-IGABT was validated by promising clinical outcomes, the future of BT for LACC is expected to progress toward the refinement of more effective image-guided procedures. Moreover, achieving operational consensus and driving technological advancements to mitigate the inherent limitations associated with different imaging modes remain essential.

PD-1 Inhibitor Maintenance Therapy Combined Iodine-125 Seed Implantation Successfully Salvage Recurrent Cervical Cancer after CCRT: A Case Report

Cervical cancer is the fourth most common cancer in females worldwide. Patients with stage III and IV cervical cancer based on the Federation of Gynecology and Obstetrics (FIGO) classification have higher recurrence rates. Because of organs at risk (OAR) protection and the low indication rate of salvage surgery, the choice of treatment is always challenging. Systemic chemotherapy is palliative and can be performed in conjunction with surgery or radiotherapy; however, it has no significant benefit to survival. Brachytherapy and stereotactic body radiotherapy (SBRT) are characterized by extremely high radiation doses applied to tumor cells while sparing the normal tissues. Several studies have investigated the efficacy of these technologies in recurrent cervical cancer and showed promising results. The immune checkpoint inhibitors approach was also investigated and showed promising results too. Herein, we report a case of a patient with cervical cancer that recurred five months after adjuvant chemotherapy and concurrent chemoradiotherapy. The disease prognosis after interstitial implantation brachytherapy (IIB) was determined. Then, the patient underwent radioactive 125I-seed implantation combined with PD-1 inhibitor treatment. The patient exhibited a partial response after seed implantation, and up to now, the duration of this partial response was 24 months.

Evaluating the accumulated dose distribution of organs at risk in combined radiotherapy for cervical carcinoma based on deformable image registration

To evaluate the feasibility and value of deformable image registration (DIR) in calculating the cumulative doses of organs at risk (OARs) in the combined radiotherapy of cervical cancer. Thirty cervical cancer patients treated with external beam radiotherapy (EBRT) combined with intracavitary brachytherapy (ICBT) were reviewed. The simulation CT images of EBRT and ICBT were imported into Varian Velocity 4.1 for the DIR-based dose accumulation. Cumulative dose-volume parameters of D2cc for rectum and bladder were compared between the direct addition (DA) and DIR methods. The quantitative parameters were measured to evaluate the accuracy of DIR. The three-dimensional cumulative dose distribution of the tumor and OARs were graphically well illustrated by composite isodose lines. In combined EBRT and ICBT, the mean cumulative bladder D2cc calculated by DIR and DA was 86.13 Gy and 86.27 Gy, respectively. The mean cumulative rectal D2cc calculated by DIR and DA was 72.97 Gy and 73.90 Gy, respectively. No significant differences were noted between these two methods (p > 0.05). As to the parameters used to evaluate the DIR accuracy, the mean DSC, Jacobian, MDA (mm) and Hausdorff distance (mm) were 0.79, 1.0, 3.84, and 22.01 respectively for the bladder and 0.53, 1.2, 7.31, and 29.58 respectively for the rectum. In this study, the DSC seemed to be slightly lower compared with previous studies. Dose accumulation based on DIR might be an alternative method to illustrate and evaluate the cumulative doses of the OARs in combined radiotherapy for cervical cancer. However, DIR should be used with caution before overcoming the relevant limitations.

The Efficacy of Volumetric Modulated Arc Therapy Combined With Chemotherapy, Brachytherapy, and Local Hyperthermia on Patients with Locally Advanced Cervical Cancer: A Retrospective Study

Objective To evaluate the clinical outcomes of volumetric modulated arc therapy (VMAT) followed by brachytherapy (BT), combined with chemotherapy, and local hyperthermia (HT) on locally advanced cervical cancer (LACC). Methods In total, 40 patients with FIGO stage IB1-IVB cervical cancer from January 2016 to December 2018 were selectively enrolled in this study. All patients were treated with VMAT (50.4 Gy/1.8 Gy/28 f) concurrent with cisplatin-based chemotherapy (40 mg/m 2 , q1w, 6 cycles) and local HT (40.5-41°C for 60 min, BIW). BT (30-36 y/5-6 f, 2 f/w) was conducted after VMAT. Objective response rate (ORR), local control (LC) time, LC rate, progression-free survival (PFS) rate, cancer-specific survival (CSS) rate, overall survival (OS), median time to tumor progression and treatment-related toxicity were evaluated. Results The median follow-up time was 31 months (8-48). The ORR was 100% at 3 months after treatment and 92.1% at 6 months, respectively. The 1-year, 2-year, and 3-year LC rates were 87.4%, 81.9%, and 70.9%, respectively. The average LC time was 31.50 ± 1.89 months (95% CI 27.79-35.21). The 1-year, 2-year, and 3-year PFS rates were 75.85%, 61.2%, and 51.3%, respectively, while the median PFS was 27.07 months. The 1-year, 2-year, and 3-year OS rates were 95%, 84%, and 79.6%, respectively. In total, 12(30%) patients had grade 3/4 bone marrow suppression. One patient had grade 4 leukopenia. In total, 17 patients had grade 1/2 bone marrow suppression. Two patients had grade 3 nausea and grade 3 vomiting reaction, respectively. No grade 3/4 proctitis and bladder reaction were observed. In the late period of treatment, 1 patient had a rectal hemorrhage. In total, 13 patients had vaginal stenosis. Conclusion VMAT concurrent with chemotherapy, BT, and local HT had a favorable short-term efficacy and acceptable toxicity on cervical cancer, which was an alternative option for LACC.