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Background: Image-guided adaptive brachytherapy (IGABT) demonstrates an excellent local control rate and low toxicity while treating cervical cancer. For intracavitary/interstitial (IC/IS) brachytherapy (BT), several applicators are commercially available. Venezia (Elekta, Sweden), an advanced gynecological applicator, is designed for IC/IS BT for treating locally advanced cervical cancer. There are two types of interstitial needles for the Venezia applicator: the round needle and sharp needle. Generally, a round needle is safer because it has less risk of damaging the organ at risk than a sharp needle. However, there is currently no evidence to suggest that a round needle is better than a sharp needle for the Venezia applicator in IC/IS BT. Herein, we documented our experience of using both round and sharp needles with the Venezia applicator in IC/IS BT for cervical cancer. Case presentation: A 71-year-old woman was diagnosed with clinical stage T2bN0M0 and the International Federation of Gynecology and Obstetrics stage IIB cervical squamous cell carcinoma. Definitive therapy, including a high-dose-rate BT boost, was planned using a round needle with the Venezia applicator in IC/IS BT. After inserting four interstitial round needles during the first and second BT sessions, an unexpectedly large gap (1.5 cm) was detected between the cervix and ovoid. We therefore used a sharp needle with the Venezia applicator for IC/IS BT during the third and fourth BT sessions. Three sharp needles were firmly inserted during the third and fourth BT sessions. Conclusions: The study findings suggest that the interstitial round needle should not be used for cervical cancer patients undergoing IC/IS BT using the Venezia applicator. [ABSTRACT FROM AUTHOR]

Background: Diffusion-weighted magnetic resonance imaging (DWI) provides a measurement of tumor cellularity. We evaluated the potential of apparent diffusion coefficient (ADC) values obtained from post-external beam radiation therapy (EBRT) DWI and prior to brachytherapy (BT) to predict for complete metabolic response (CMR) in bulky cervical cancer. Methods: Clinical and DWI (b value = 500 s/mm2) data were obtained from patients undergoing interstitial BT with high-risk clinical target volumes (HR-CTVs) > 30 cc. Volumes were contoured on co-registered T2 weighted images and 90th percentile ADC values were calculated. Patients were stratified by CMR (defined by PET-CT at three months post-BT). Relation of CMR with 90th percentile ADC values and other clinical factors (International Federation of Gynecology and Obstetrics (FIGO) stage, histology, tumor and HR-CTV size, pre-treatment hemoglobin, and age) was assessed both in univariate and multivariate logistic regression analyses. Youden's J statistic was used to identify a threshold value. Results: Among 45 patients, twenty-eight (62%) achieved a CMR. On univariate analysis for CMR, only 90th percentile ADC value was significant (p = 0.029) while other imaging and clinical factors were not. Borderline significant factors were HR-CTV size (p = 0.054) and number of chemotherapy cycles (p = 0.078). On multivariate analysis 90th percentile ADC (p < 0.0001) and HR-CTV size (p < 0.003) were highly significant. Patients with 90th percentile ADC values above 2.10 × 10− 3 mm2/s were 5.33 (95% CI, 1.35–24.4) times more likely to achieve CMR. Conclusions: Clinical DWI may serve to risk-stratify patients undergoing interstitial BT for bulky cervical cancer. [ABSTRACT FROM AUTHOR]

Purpose: This study retrospectively compared the clinical and toxicity outcomes for the cervical cancer of the MRI-guided two adaptive brachytherapy (IGABT) fractions versus one IGABT fraction in one application. Methods: One hundred and twenty patients with cervical cancer received external beam radiotherapy combined with or without concurrent chemotherapy, which was followed by the IGABT. The IGABT in 63 patients had one IGABT in each application (Arm 1), while in the other 57 patients, at least one treatment was two continuous IGABT every other day in one application (Arm 2). Clinical outcomes including overall survival (OS), cancer specific survival (CSS), progression free survival (PFS), local control (LC) were analyzed. Brachytherapy-related toxicities were evaluated, which included pain, dizziness, nausea/vomiting, fever/infection, blood loss during the removal of applicator and needles, the deep venous thrombosis, and other acute toxicities. The Common Terminology Criteria for Adverse Events (CTC-AE 5.0) was used to evaluate the incidence and severity of toxicities of the urinary system, lower digestive system, and reproduction system. Kaplan–Meier and the Log-rank test were used to analyze the clinical outcomes. Results: The median follow-up time of the patients in Arm 1 and Arm 2 was 23.5 and 12.0 months, respectively. The overall treatment time was significantly shorter in Arm 2 than Arm 1 (60 vs. 64 d; P = 0.017). The OS, CSS, PFS, and LC in Arm1 and Arm 2 was 77.8% vs. 86.0% (P = 0.632), 77.8% vs. 87.7% (P = 0.821), 68.3% vs. 70.2% (P = 0.207), and 92.1% vs. 94.7% (P = 0.583), respectively. The highest NRS of the pain during brachytherapy waiting period (2.22 ± 1.84 vs. 3.02 ± 1.65; P < 0.001) and at the time of the removal of the applicator (4.69 ± 1.49 vs. 5.30 ± 1.18; P < 0.001) in the patients who received one hybrid intracavitary and interstitial brachytherapy (IC/ISBT) in one application and two continuous IC/ISBT every other day in one application were significantly different. So far four patients with grade 3 late toxicities have been reported. Conclusions: The findings of this study demonstrated that the two continuous IGABT every other day in one application is a logistically applicable, safe, and effective treatment strategy that could shorten the overall treatment time and reduce the medical cost, comparing with the one IGABT in one application. [ABSTRACT FROM AUTHOR]

Background: Radiotherapy (RT) destroys cancer cells and activates the immune system while suppressing the immunity of tumor-associated tissues, including the tumor microenvironment (TME). However, to date, no anti-tumor therapeutic strategy that uses these immune mechanisms has been established. This study investigated changes in the immunity of the TME during standard radical RT for cervical cancer combined with external beam RT and brachytherapy and determined whether these changes affect prognosis. Methods: Twenty-six patients who had completed radical RT for cervical cancer were categorized into the following two groups according to whether the cancer recurred and/or metastasized within 2 years after the start of treatment: treatment failure (n = 14) and treatment success (n = 12). We assessed the expression of programmed death 1, programmed death ligand 1 (PD-L1), cluster of differentiation (CD) 8, CD68, CD163, Forkhead box protein P3, and hypoxia-inducible factor-1α in the TME of cervical tissues collected periodically during treatment and evaluated the difference in expression rates of each marker between the success and failure groups and assessed its effect on prognosis. Results: The expression levels of PD-L1 and CD163 in the TME in the treatment success group were lower than those in the treatment failure group at the midpoint during brachytherapy (p < 0.01 and p = 0.08, respectively), and the 2-year progression-free-survival (PFS) rate depended on the expression levels of PD-L1 and CD163 (p = 0.04 and p = 0.02, respectively). Conclusions: The expression rates of CD163 and PD-L1 in the TME during brachytherapy were related to treatment response and the 2-year PFS. This study may increase our understanding of tumor-associated immunity in the TME and aid in the development of therapies targeting PD-L1 or M2 macrophages in the TME in conjunction with RT, especially brachytherapy, for cervical cancer patients. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this study was to explore the influence of individual patient factors, such as volume of the planning target volume (PTV) (VPTV), cardiothoracic ratio (CTR), central lung distance (CLD), and maximal heart distance (MHD), on the design of treatment plans in terms of target dose coverage, integral dose, and dose to organs at risk (OAR) in early breast cancer. Methods: Ninety-six patients were selected for this study. Radiation doses of 50 Gy and a simultaneous dose of 60 Gy in 25 fractions were administered to the whole breast and tumor bed, respectively. The intensity modulation plan (IMRT) of each patient uses both physical parameters and an equivalent uniform dose (EUD) to optimize the target function. Univariate and multivariate linear regression were used to analyze the relationship between predictive impact factors and OAR percent dose volume, conformity index (CI), and homogeneity index (HI). Results: The average CI and HI values of the left breast cancer plan were 0.595 ± 0.071 (0.3–0.72) and 1.095 ± 0.023 (1.06–1.18), respectively. The CTR (B = 0.21, P = 0.045), VPTV (B = 0.63, P = 0.000), volume of the lung (Vlung) (B = − 0.29, P = 0.005), and MHD (B = 0.22, P = 0.041) were identified as factors influencing the CI index of the left breast cancer intensity modulation plan. VPTV (B = 1.087, P = 0.022) was identified as the influencing factor of the HI index of the left breast cancer intensity modulation plan. volume of the heart (Vheart) (B = − 0.43, P = 0.001) and CLD (B = 0.28, P = 0.008) were influencing factors of the volume of lung (Vlung20) of the lung. The prediction formulas for left-sided breast cancer are noted as follows: CI = 0.459 + 0.19CTR-0.16CLD, Vlung10 = 35.5–0.02Vheart; and Vlung20 = 21.48 + 2.8CLD-0.018Vheart. Conclusions: CTR, CLD, and MHD can predict the rationality of the parameters of the left breast cancer IMRT. The calculation formula generated based on this information can help the physicist choose the optimal radiation field setting method and improve the quality of the treatment plan. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate prognosis for reducing postoperative radiotherapy (PORT) dose to lymph node levels of supraglottic cancer (SC) on real-world data. Method and materials: Patients were derived from two cancer centers. In center 1, the involved nodal levels (high-risk levels, HRL) and the next level received a dose of 60.06 Gy/1.82 Gy per fraction, while the other uninvolved levels (low-risk levels, LRL) received 50.96 Gy/1.82 Gy per fraction. In center 2, all received 50 Gy/2 Gy per fraction. The rates of high-risk levels control (HRC), regional control (RC), overall survival (OS), progression-free survival (PFS) and distant metastasis-free survival (DMFS) were calculated by Kaplan–Meier method. Result: Totally, 124 patients were included (62 in center 1, 62 in center 2). Most patients (106, 85.5%) had a stage T3/N + tumor. The median follow-up was 45 months (range 1–163 months). There were no significant differences in terms of OS (p = 0.126), RC (p = 0.514), PFS (p = 0.195) and DMFS (p = 0.834). Most regional recurrences (4, 80%) occurred within three years of treatment, and all occurred within the target volumes. No regional failure occurred in HRL in center 1, while three (3/4) failures occurred in center 2. Dose reduction prescription to HRL led to a lower HRC rate (100% vs. 90.6%, p = 0.009). While the rates of LRL control (98.4%) were equal between the two centers. Conclusion: Compared with a standard dose, the reduced dose to involved nodal levels showed inferior regional control for PORT, while uninvolved nodal levels showed equal outcomes. A dose of 50 Gy for HRL may be an unfavorable treatment option for SC. [ABSTRACT FROM AUTHOR]

Background: Similar to other local therapeutic methods, local interstitial radiotherapy (IRT) also suffers from insufficient systematic immune activation, resulting in tumor metastasis. Results: Mn-based IRT radiosensitizers consisting of 131I, MnO2 and bovine serum albumin (BSA) (131I-MnO2-BSA) were engineered. Such Mn-based IRT radiosensitizers successfully unlocked radiogenetics to magnify systematic immune responses of local IRT via remodeling hypoxic and immunosuppressive microenvironments and resist tumor metastasis. The MnO2 in 131I-MnO2-BSA caused decomposition of H2O2 enriched in tumors to generate O2 for alleviating hypoxic microenvironment and removing tumor resistances to IRT. Concurrently, hypoxia mitigation by such radiosensitizers-unlocked radiogenetics can effectively remodel immunosuppressive microenvironment associated with regulatory T (Treg) cells and tumor-associated macrophages (TAMs) infiltration inhibition to induce immunogenic cell death (ICD), which, along with hypoxia mitigation, activates systematic immune responses. More intriguingly, 131I-MnO2-BSA-enabled radiogenetics can upregulate PD-L1 expression, which allows anti-PD-L1-combined therapy to exert a robust antitumor effect on primary tumors and elicit memory effects to suppress metastatic tumors in both tumor models (4T1 and CT26). Conclusions: IRT radiosensitizer-unlocked radiogenetics and the corresponding design principle provide a general pathway to address the insufficient systematic immune responses of local IRT. [ABSTRACT FROM AUTHOR]

Background: Image-guided adaptive brachytherapy shows the ability to deliver high doses to tumors while sparing normal tissues. However, interfraction dose delivery introduces uncertainties to high dose estimation, which relates to normal tissue toxicity. The purpose of this study was to investigate the high-dose regions of two applicator approaches in brachytherapy.Method: For 32 cervical cancer patients, the CT images from each fraction were wrapped to a reference image, and the displacement vector field (DVF) was calculated with a hybrid intensity-based deformable registration algorithm. The fractional dose was then accumulated to calculate the position and the overlap of high dose (D2cc) during multiple fractions.Result: The overall Dice similarity coefficient (DSC) of the deformation algorithm for the bladder and the rectum was (0.97 and 0.91). No significant difference was observed between the two applicators. However, the location of the intracavitary brachytherapy (ICBT) high-dose region was relatively concentrated. The overlap volume of bladder and rectum D2cc was 0.42 and 0.71, respectively, which was higher than that of interstitial brachytherapy (ISBT) (0.26 and 0.31). The cumulative dose was overestimated in ISBT cases when using the GEC-recommended method. The ratio of bladder and rectum D2cc to the GEC method was 0.99 and 1, respectively, which was higher than that of the ISBT method (0.96 and 0.94).Conclusion: High-dose regions for brachytherapy based on different applicator types were different. The 3D-printed ICBT has better high-dose region consistency than freehand ISBT and hence is more predictable. [ABSTRACT FROM AUTHOR]