Journal

Strahlentherapie und Onkologie

Papers (38)

Association of long-term treatment outcomes with changes in PET/MRI characteristics and the type of early treatment response during concurrent radiochemotherapy in patients with locally advanced cervical cancer

Abstract Purpose We aimed to find predictive tumour characteristics as detected by interim positron-emission tomography/magnetic resonance imaging (PET/MRI) in cervical cancer patients. We also investigated the type of interim response. Furthermore, we compared the investigated parameters with disease-free (DFS) and overall survival (OS) outcomes. Methods We evaluated 108 patients treated between August 2015 and January 2023 with external-beam radiotherapy (EBRT) and image-guided adaptive brachytherapy (IGABT) who had undergone pretreatment staging, subsequent mid-treatment evaluation after completed EBRT and definitive restaging 3 months after completing the whole treatment using PET/MRI. Patients were then divided into two groups based on the RECIST and PERCIST criteria: responders (achieving complete metabolic response, CMR) and non-responders (non-CMR). These two groups were compared using selected parameters obtained at pre-PET/MRI and mid-PET/MRI. The early response to treatment as evaluated by mid-PET/MRI was categorized into three types: interim complete metabolic response, interim nodal response and interim nodal persistence. Results Mid-TLG‑S (the sum of total lesion glycolysis for the primary tumour plus pelvic and para-aortic lymph nodes) parameter showed the best discriminatory ability for predicting non-CMR. The second factor with significant discriminatory ability was mid-MTV‑S (the sum of the metabolic tumour volume of the primary tumour plus pelvic and para-aortic lymph nodes). The strongest factor, mid-TLG‑S, showed a sensitivity of 40% and a specificity of 90% at a threshold value of 70. We found a statistically significant association of DFS and OS with the following parameters: number of chemotherapy cycles, early response type and CMR vs. non-CMR. Conclusion We were able to identify thresholds for selected parameters that can be used to identify patients who are more likely to have worse DFS and OS. The type of early response during concurrent chemoradiotherapy (CCRT) was also significantly associated with DFS and OS. These aspects represent an important contribution to the possible stratification of patients for subsequent individualised adjuvant treatment.

Treatment outcomes of MRI-guided adaptive brachytherapy in patients with locally advanced cervical cancer: institutional experiences

Image-guided adaptive brachytherapy (IGABT) is currently state of the art in the comprehensive treatment of patients with cervical cancer. Here, we report mature clinical data regarding IGABT of cervical cancer in a large patient sample, examining clinical outcomes, manifestations of late toxicities, and dosimetric findings. Between May 2012 and October 2020, we performed a total of 544 uterovaginal IGABT applications in 131 consecutive patients with biopsy-proven cervical carcinoma not suitable for surgery. The median duration of follow-up was 43 months. The estimated 3‑, 4‑, and 5‑year LC rates were 88.3% (95% confidence interval [CI] 81.1-95.5), 86.9% (95% CI 78.5-95.3), and 85.5% (95% CI 76-95%), respectively. The 3‑, 4‑, and 5‑year OS estimates were 72.66% (95% CI 63.64-81.69%), 68.9% (95% CI 59.15-78.66%), and 63.96% (95% CI 52.94-74.97%), respectively. Patients who received ≥ 5 cycles of chemotherapy had statistically significantly better 3‑year recurrence-free survival (RFS) compared to patients who completed <5 cycles (79.07% [95% CI 60.81-97.34] vs. 58.10% [95% CI 47.22-68.98]; p = 0.0185). We recorded manifestations of genitourinary and gastrointestinal toxicity grade ≥3 in 6.9% and 5.3%, respectively. Our mature long-term data on the treatment patients with locally advanced cervical cancer show that excellent treatment outcomes can be achieved with MRI-based IGABT, as well as acceptable late morbidity.

Is model-based dose calculation based on cone-beam computed tomography suitable for adaptive treatment planning in brachytherapy?

Abstract Background and purpose Model-based dose calculation considering tissue compositions is increasingly being investigated in brachytherapy. The aim of this study was to assess the suitability of modern cone-beam computed tomography (CBCT) imaging compared to conventional computed tomography (CT) scans for this purpose. Materials and methods By means of a phantom study, we evaluated the CT numbers and electron densities measured using a modern CBCT device as well as a conventional CT scanner for various materials. Based on this, we compared dose calculations (using the TG-43 formalism as well as model-based collapsed cone calculations assuming uniform materials [ACEuniform] and considering CT numbers [ACECT#]) on planning CTs and control CBCTs for patients with cervical and breast cancer as well as phantom-simulated skin cancer cases. Assessing dosimetric deviations between the planning CTs and control CBCTs acquired during the treatment course served to estimate interfractional implant variations. Results The comparison of ACEuniform–ACECT# deviations between planning CTs and control CBCTs revealed no statistically significant difference for almost all examined dose parameters. Dosimetric deviations between model-based dose calculations and TG-43 were partly significant but of small magnitude (&lt; 10 cGy per fraction). Interfractional dosimetric variations were substantially larger than the dosimetric differences found between the various dose calculation procedures. Conclusion Model-based dose calculation based on modern CBCT imaging was suitable. However, the found differences between these calculations and the TG-43 formalism should be investigated in dose–outcome analyses. The observed interfractional dosimetric variations revealed the importance of performing treatment quality assurance.

Multimodal chemoradiotherapy including interstitial brachytherapy enhances outcomes in FIGO stage IVA cervical cancer: a focus on tumor control and quality of life

Abstract Purpose This study was performed to evaluate the outcomes of advanced radiotherapy techniques, including image-guided adaptive brachytherapy (IGABT), in International Federation of Gynecology and Obstetrics (FIGO) stage IVA cervical cancer patients with adjacent organ infiltration. A further aim was to identify prognostic factors influencing overall survival (OS) and local control (LC) in these patients, with a particular focus on toxicity and patient-reported outcomes (PROs). Methods This retrospective, single-center study included 31 patients with FIGO stage IVA cervical cancer treated with definitive chemoradiotherapy between 2010 and 2020. All 31 patients underwent external-beam radiotherapy (EBRT), with concurrent cisplatin-based chemotherapy (CTX) administered in 25 cases and additional high-dose-rate brachytherapy (BT) performed in 24 cases. Treatment-related adverse events were categorized in accordance with the Common Terminology Criteria for Adverse Events (CTCAE; version 5.0) [1]. PROs were evaluated using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire version 3.0 (EORTC QLQ-C30), while sexual function was assessed through three specific questions adapted from the EORTC QLQ-BR23 module. Results Median OS was estimated at 51.7 months, with 2‑ and 5‑year OS rates of 58.1 and 46.2%, respectively. Median progression-free survival (PFS) was 48.1 months (95% CI: 0–96.2 months), with 2‑ and 5‑year PFS rates of 52 and 37%. The 10-year LC probability was 70.4%, showing a significant association with improved OS (p = 0.0039). Eastern Cooperative Oncology Group (ECOG) performance status (p = 0.014) and nodal involvement were identified as prognostic factors. The estimated median OS was 108 months for patients treated with BT and 51.7 months for those without. Patients receiving six fractions or a cumulative BT dose of ≥ 24 Gy demonstrated improved 5‑year OS rates of 62.3%, although the difference was not statistically significant. Acute toxicities were reported in 83.9% of patients, primarily grades 1–2, with severe complications such as fistula formation occurring in 16.1%. Late toxicities, predominantly affecting the gastrointestinal and urogenital systems, were observed in 45.2% of patients. Patient-reported outcomes indicated mild to moderate impairments of quality of life, with fatigue and gastrointestinal symptoms being the most frequently reported issues. Conclusion Advanced radiotherapy, particularly IGABT, achieves durable LC in patients with FIGO stage IVA cervical cancer, supporting its use as a cornerstone of curative-intent treatment. However, systemic progression remains a major challenge, highlighting the need for novel therapeutic strategies, including immunotherapy and liquid biopsy for treatment monitoring. Future prospective trials are essential to validate these findings and refine therapeutic protocols, particularly for high-risk subgroups. Ensuring equitable access to these advanced treatments is critical for improving global outcomes in cervical cancer care.

Investigation of potential biomarkers associated with relapse in cervical cancer: miRNA-320a-3p and miRNA-136-5p

Micro ribonucleic acids (miRNAs) are short non-coding RNA molecules that control the expression of target mRNAs. Many miRNAs are dysregulated in various cancers, acting as tumor suppressors or oncogenes. This study aims to investigate the regulatory status of miRNA-320a-3p and miRNA-136-5p in cervical cancer development as well as their predictive significance for treatment response and disease recurrence. Included in the study were 51 cervical cancer patients and 19 healthy controls. Expression levels of miRNA-320a-3p and miRNA-136-5p were detected using miRNA-specific quantitative real-time polymerase chain reaction (PCR). The relative expression of miRNAs was calculated using the 2 miRNA-136-5p was downregulated in the cervical cancer patients compared to the controls (fold change: -3.06, p = 0.000239). In the case group, upregulation of miRNA-320a-3p was significantly associated with a poor treatment response (fold change: 1.88, p = 0.0264). Additionally, higher expression of miRNA-320a-3p was observed in patients with locoregionally confined recurrence both in the evaluation based on initial recurrence patterns (fold change: 1.38, p = 0.0341) and at last follow-up (fold change: 2.56, p = 0.000582). miRNA-136-5p can be proposed as a biomarker in cervical tumorigenesis, while miRNA-320a-3p can be used for treatment response and locoregional recurrence prediction.

Long-term analysis of hematological parameters as predictors of recurrence patterns and treatment outcomes in cervical cancer patients undergoing definitive chemoradiotherapy

Abstract Purpose This study sought to determine the predictive and prognostic value of clinicopathological parameters and neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and hemoglobin (Hgb) level in predicting recurrence patterns and locoregional relapse-free survival (LRFS) and distant metastasis-free survival (DMFS) in cervical cancer patients receiving definitive chemoradiotherapy (ChRT). Methods This study included 261 cervical cancer patients treated with ChRT. The primary endpoints were the predictors of local recurrence (LR) and distant metastasis (DM), whereas the secondary endpoints were LRFS and DMFS. The association of survival with potential prognostic factors was analyzed using Cox regression analysis, and the predictors of LR and DM were identified using logistic regression analysis. Results The median follow-up time was 10.9 years. Recurrences occurred in 132 patients (50.6%) within a median of 11.2 months after definitive ChRT. NLR and PLR values were significantly higher in patients with LR and DM than in those without, with no significant differences in Hgb levels in patients with or without LR and DM. In the multivariable logistic regression analysis, lymph node metastasis, elevated NLR, and low Hgb level were significantly correlated with LR and DM. In the multivariable analysis, large tumor size, presence of lymph node metastasis, and elevated NLR were the independent predictors for poor LRFS and DMFS, and Hgb level was an additional prognostic factor for DMFS. Conclusion Hematological markers, particularly NLR and Hgb, may serve as cost-effective and readily accessible indicators for predicting recurrence and survival in cervical cancer patients, contributing to their practical use in routine assessments.

An easy way to determine bone mineral density and predict pelvic insufficiency fractures in patients treated with radiotherapy for cervical cancer

Abstract Purpose The aim of this study was to investigate whether bone mineral density (BMD) as measured in planning computed tomographies (CTs) by a new method is a risk factor for pelvic insufficiency fractures (PIF) after radio(chemo)therapy (R(C)T) for cervical cancer. Methods 62 patients with cervical cancer who received definitive or adjuvant radio(chemo)therapy between 2013 and 2017 were reviewed. The PIF were detected on follow-up magntic resonance imaging (MRI). The MRI of the PIF patients was registered to the planning CT and the PIF contoured. On the contralateral side of the fracture, a mirrored structure of the fracture was generated (mPIF). For the whole sacral bone, three lumbar vertebrae, the first and second sacral vertebrae, and the PIF, we analyzed the BMD (mg/cm3), V50Gy, Dmean, and Dmax. Results Out of 62 patients, 6 (9.7%) had a fracture. Two out of the 6 patients had a bilateral fracture with only one of them being symptomatic. PIF patients showed a significantly lower BMD in the sacral and the lumbar vertebrae (p &lt; 0.05). The BMD of the contoured PIF, however, when comparing to the mPIF, did not reach significance (p &lt; 0.49). The difference of the V50Gy of the sacrum in the PIF group compared to the other (OTH) patients, i.e. those without PIF, did not reach significance. Conclusion The dose does not seem to have a relevant impact on the incidence of PIF in our patients. One of the predisposing factors for developing PIF after radiotherapy seems to be the low BMD. We presented an easy method to assess the BMD in planning CTs.

Impact of intracavitary brachytherapy technique (2D versus 3D) on outcomes of cervical cancer: a systematic review and meta-analysis

To perform a systematic review and meta-analysis of the impact of brachytherapy (BT) technique (two-dimensional [2D] or three-dimensional image-guided [3D]) on outcomes of cervical cancer patients. PubMed and EMBASE databases were searched up to April 16, 2019, for studies which evaluated the effect of 3D-BT compared to 2D-BT in cervical cancer. Endpoints included cumulative incidence of severe toxicity, locoregional recurrence-free survival (LRRFS), progression-free survival (PFS), and overall survival (OS). Hazard ratios (HRs) were pooled in the meta-analysis using the random-effects model. Six studies of eight cohorts were included in the quantitative synthesis. The pooled HR regarding toxicity was evaluated in five cohorts in three studies, and the HR of 3D-BT compared to 2D-BT was 0.54 (95% confidence interval [CI] 0.37-0.77). All six studies were included for the synthesis for LRRFS, and the pooled HR favors 3D-BT (0.61 [95% CI 0.40-0.93]). For PFS, three studies were included for analysis and 3D-BT was superior to 2D-BT (HR = 0.75 [95% CI 0.59-0.96]). Five studies were included for the pooled HR regarding OS, and pooled HR of 3D-BT compared to 2D-BT was 0.65 (95% CI 0.40-1.06). 3D-BT might reduce severe toxicity and improve LRRFS and PFS in patients with cervical cancer. 3D-BT should be considered for standard management of cervical cancer, and efforts for adopting this procedure in Korea should be pursued.

Prediction of treatment response in patients with locally advanced cervical cancer using midtreatment PET/MRI during concurrent chemoradiotherapy

We aimed to find metabolic, functional or morphological characteristics of the tumor predicting failure to achieve complete metabolic remission (CMR) by the midtreatment PET/MRI (positron emission tomography/magnetic resonance imaging) in cervical cancer patients. We evaluated 66 patients treated between August 2015 and November 2019 who underwent pretreatment staging, subsequent midtreatment evaluation, and definitive restaging 3 months after completing the whole treatment, all using PET/MRI. The pretreatment parameters (pre-SUVmax, pre-SUVmean, pre-MTV, pre-MTV‑S, pre-TLG, pre-TLG‑S [SUV: standard uptake value, MTV: metabolic tumor volume, TLG: total lesion glycolysis]), and the midtreatment parameters at week 5 during chemoradiotherapy (mid-SUVmax, mid-SUVmean, mid-MTV, mid-MTV‑S, mid-TLG and mid-TLG-S) were recorded. The value of ADC (apparent diffusion coefficient) was also measured. Furthermore, we recorded absolute and relative changes in all parameters-∆ and ∆%. We divided the whole group of patients into "responders" (CMR) and "non-responders" (non-CMR), and compared them on the basis of the parameters from pre-PET/MRI and mid-PET/MRI. A statistically significant difference in the evaluated parameters between responders and non-responders was found for the following parameters: mid-MTV, mid-TLG, mid-TLG‑S, mid-MTV‑S, mid-tumor size, and ∆%SUVmax. According to the ROC (receiver operating characteristic) analysis, mid-MTV‑S showed the best albeit moderate discrimination ability for the prediction of non-CMR. Significant mutual correlations of all variables, in particular between mid-MTV‑S and mid-TLG‑S and between mid-MTV and mid-TLG, were found (all p < 0.05). Our study confirmed that when using the midtreatment PET/MRI we are able to identify metabolic parameters having the discrimination ability for the prediction of non-CMR. In particular mid-MTV‑S, mid-MTV, mid-tumor size, mid-TLG‑S, mid-TLG and ∆%SUVmax.

Outcome analysis of HDR compared to PDR IGABT in locally advanced cervical cancer: a single-center cohort analysis

This monocentric study aimed to assess the impact of technical advancement in brachytherapy (BT) on local control (LC) and cancer-specific survival (CSS) in locally advanced cervical cancer (LACC). Since 2010, 211 patients with LACC have been treated with 45/50.4 Gy or 60 Gy radiochemotherapy (RTCT) followed by image-guided adaptive brachytherapy (IGABT) at the authors' institution. In 2013, combined intracavitary and interstitial brachytherapy (BT IC/IS) was implemented and in 2018, pulsed-dose-rate BT (PDR-BT) was replaced by high-dose-rate BT (HDR-BT). LC, CSS, and morbidity according to the RTOG/EORTC scoring system were analyzed. Dose-volume parameters for the high-risk clinical target volume (HRCTV) and organs at risk (OAR) were reported. While 27 (12.8%) patients died of LACC, complete local remission was achieved in 199 (94.3%). Local relapse decreases with a high D95 in the HRCTV (hazard ratio, HR = 0.85, p = 0.0024). D95 in the HRCTV is lower after 60 Gy even if interstitial BT is used. Mean D95 in the HRCTV is 78.2 Gy, 83.3 Gy, and 83.4 Gy with PDR-BT IC, PDR-BT IC/IS, and HDR-BT IC/IS, respectively, after 45/50.4 Gy. D2 cc of OARs is significantly reduced by using interstitial BT. The mean rectum and sigmoid D2 cc are about 61.5 Gy with PDR-BT IC/IS and significantly decreased with HDR-BT IC/IS. This translates into a low fistula incidence. A very low rate of severe gastrointestinal (3.4%) and genitourinary (2.3%) toxicity was observed with HDR-BT IC/IS. This large monocentric study provides further evidence that implementation of BT IC/IS has an impact on D95 in the HRCTV, LC, and CSS. There are no differences between HDR and PDR in terms of efficacy, D95 in the HRCTV, and toxicity grade ≥ 3.

Evaluating dosimetric parameters predictive of hematologic toxicity in cervical cancer patients undergoing definitive pelvic chemoradiotherapy

We performed a retrospective study of cervical cancer pelvic radiotherapy plans to explore dosimetric parameters predictive of hematologic toxicity (HT), with specific interest in evaluating metabolic parameters and identifying the best predictive model. Active marrow was retroactively contoured as pelvic bone with SUV > mean on 18F-FDG-PET. "Highly active" marrow was contoured as the hottest 10-14% volume of active marrow. Pelvic bone contour was segmented into lumbosacral, iliac crest, and lower pelvis. Predictors of HT were evaluated using logistic regression and repeated measures modeling. One hundred women were evaluated from 2009 to 2020. The plurality/majority had stage IIIC1 disease (38%) and underwent IMRT (88%) with pelvic field alone (72%). The majority received weekly cisplatin (78%), and 82% completed at least five cycles. The most common HT was leukopenia (grade 2+: 68%). Predictors of grade 2+ and 3+ HT were baseline WBC (p < 0.001), and 10- and 20-Gy dosimetric parameters to the active marrow, highly active marrow, and pelvic bone. The best predictive model of leukocyte trajectory included baseline WBC (p < 0.001), highly active marrow V20 (p < 0.001), and interactions of baseline WBC with time (p < 0.001) and highly active marrow V20 (p < 0.001), such that those with low baseline WBC experienced the greatest impact of highly active marrow V20. Baseline WBC was highly predictive of HT; dosimetric predictors included dose to the active marrow, highly active marrow, and pelvic bone, with the greatest impact from V20 to the highly active marrow, particularly in women with low baseline WBC. Future studies should consider incorporating baseline WBC and limiting dose to the most highly active marrow.

Analysis of operative duration of image-guided brachytherapy for cervical cancer

The present study aimed to analyze the operative duration of image-guided brachytherapy (IGBT) for cervical cancer performed at our institution. We enrolled cervical cancer patients who had undergone tandem and ovoid-based intracavitary brachytherapy (ICBT) or intracavitary and interstitial brachytherapy (IC/ISBT) between 2020 and 2024. Cone beam computed tomography (CBCT), CT, or CT + MRI were used for IGBT. For each IGBT session, we retrospectively reviewed the following: application time (AT-defined as the duration from entry into the operating room to the initial image acquisition); planning time (PT-defined as the duration from the initial image acquisition to the start of irradiation); and total operation time (TOT- defined as the duration from entry to exit of the operating room). We analyzed a total of 126 sessions in 36 patients, consisting of 99 ICBT-only sessions and 27 IC/ISBT sessions. The IC/ISBT sessions had a significantly longer mean operative duration than the ICBT-only sessions. The IC/ISBT sessions with three or more interstitial needles had significantly longer AT and TOT. However, the IC/ISBT sessions with one needle showed no significant difference in operative duration compared to ICBT-only sessions. CBCT, CT, and CT + MRI were used in 42, 76, and 8 sessions, respectively. In the ICBT patients, CT + MRI had the longest PT. However, there was no significant differences in TOT among CBCT, CT, and CT + MRI. IC/ISBT sessions with one needle had no significant difference in operative duration compared to ICBT-only sessions. There was no significant difference in TOT between CT + MRI-based IGBT and CT-based IGBT.

Biological treatment evaluation in thermoradiotherapy: application in cervical cancer patients

Abstract Background Hyperthermia treatment quality is usually evaluated by thermal (dose) parameters, though hyperthermic radiosensitization effects are also influenced by the time interval between the two modalities. This work applies biological modelling for clinical treatment evaluation of cervical cancer patients treated with radiotherapy plus hyperthermia by calculating the equivalent radiation dose (EQDRT, i.e., the dose needed for the same effect with radiation alone). Subsequent analyses evaluate the impact of logistics. Methods Biological treatment evaluation was performed for 58 patients treated with 23–28 fractions of 1.8–2 Gy plus 4–5 weekly hyperthermia sessions. Measured temperatures (T50) and recorded time intervals between the radiotherapy and hyperthermia sessions were used to calculate the EQDRT using an extended linear quadratic (LQ) model with hyperthermic LQ parameters based on extensive experimental data. Next, the impact of a 30-min time interval (optimized logistics) as well as a 4‑h time interval (suboptimal logistics) was evaluated. Results Median average measured T50 and recorded time intervals were 41.2 °C (range 39.7–42.5 °C) and 79 min (range 34–125 min), respectively, resulting in a median total dose enhancement (D50) of 5.5 Gy (interquartile range [IQR] 4.0–6.6 Gy). For 30-min time intervals, the enhancement would increase by ~30% to 7.1 Gy (IQR 5.5–8.1 Gy; p &lt; 0.001). In case of 4‑h time intervals, an ~ 40% decrease in dose enhancement could be expected: 3.2 Gy (IQR 2.3–3.8 Gy; p &lt; 0.001). Normal tissue enhancement was negligible (&lt; 0.3 Gy), even for short time intervals. Conclusion Biological treatment evaluation is a useful addition to standard thermal (dose) evaluation of hyperthermia treatments. Optimizing logistics to shorten time intervals seems worthwhile to improve treatment efficacy.

Hybrid TRUS/CT with optical tracking for target delineation in image-guided adaptive brachytherapy for cervical cancer

Abstract Objective To prospectively compare the interobserver variability of combined transrectal ultrasound (TRUS)/computed tomography (CT)- vs. CT only- vs. magnetic resonance imaging (MRI) only-based contouring of the high-risk clinical target volume (CTVHR) in image-guided adaptive brachytherapy (IGABT) for locally advanced cervical cancer (LACC). Methods Five patients with LACC (FIGO stages IIb–IVa) treated with radiochemotherapy and IGABT were included. CT, TRUS, and T2-weighted MRI images were performed after brachytherapy applicator insertion. 3D-TRUS image acquisition was performed with a customized ultrasound stepper device and software. Automatic applicator reconstruction using optical tracking was performed in the TRUS dataset and TRUS and CT images were fused with rigid image registration with the applicator as reference structure. The CTVHR (based on the GEC-ESTRO recommendations) was contoured by five investigators on the three modalities (CTVHR_CT, CTVHR_TRUS-CT, and CTVHR_MRI). A consensus reference CTVHR_MRI (MRIref) was defined for each patient. Descriptive statistics and overlap measures were calculated using RTslicer (SlicerRT Community and Percutaneous Surgery Laboratory, Queen’s University, Canada), comparing contours of every observer with one another and with the MRIref. Results The interobserver coefficient of variation was 0.18 ± 0.05 for CT, 0.10 ± 0.04 for TRUS-CT, and 0.07 ± 0.03 for MRI. Interobserver concordance in relation to the MRIref expressed by the generalized conformity index was 0.75 ± 0.04 for MRI, 0.51 ± 0.10 for TRUS-CT, and 0.48 ± 0.06 for CT. The mean CTVHR_CT volume of all observers was 71% larger than the MRIref volume, whereas the mean CTVHR_TRUS-CT volume was 15% larger. Conclusion Hybrid TRUS-CT as an imaging modality for contouring the CTVHR in IGABT for LACC is feasible and reproducible among multiple observers. TRUS-CT substantially reduces overestimation of the CTVHR volume of CT alone while maintaining similar interobserver variability.

Assessment of needle bending and tracking requirements for optimized needle placement in combined intracavitary/interstitial gynecologic brachytherapy

Abstract Purpose Needle tracking using external prediction techniques such as optical tracking is a modern approach aimed at improving implantation accuracy in gynecologic brachytherapy. This study aims to investigate the corresponding impact of needle bending in situ and to analyze needle path deviations from the intended locations occurring in our current clinical workflow that only considers ultrasound imaging without tracking. Methods We developed a semi-automated approach for reconstructing brachytherapy needles based on planning CTs and compared the respective accuracy to the also determined intra-observer variability of manual reconstructions. Based on this, we measured needle bending in situ for 89 patients and calculated the Euclidean distances between actual needle tips and needle tip predictions both longitudinally and laterally to the insertion direction. Furthermore, we compared actual and intended spacings between inserted needles to estimate implantation uncertainties with respect to our current clinical workflow. Results Our developed reconstruction featured an accuracy of 0.17 ± 0.08 mm, which was improved compared to the intra-observer variability of 0.21 ± 0.11 mm. Needle bending depended strongly on needle length and ranged from 3.6 ± 2.1 mm for 100–120 mm needles up to 7.9 ± 3.0 mm for 200–220 mm needles. Deflections in the transverse direction were substantially higher than tip deviations in the longitudinal direction. Furthermore, we found deviations from an equidistant spacing between needle paths of 1.4 ± 1.2 mm in the transverse direction. Conclusion Inserting brachytherapy needles can be substantially affected by transverse needle bending in situ, which should therefore be corrected for in prediction approaches such as optical tracking.

Conventional 3D conformal radiotherapy and volumetric modulated arc therapy for cervical cancer: Comparison of clinical results with special consideration of the influence of patient- and treatment-related parameters

Abstract Purpose Intensity-modulated radiotherapy (IMRT) for cervical cancer yields favorable results in terms of oncological outcomes, acute toxicity, and late toxicity. Limited data are available on clinical results with volumetric modulated arc therapy (VMAT). This study’s purpose is to compare outcome and toxicity with VMAT to conventional 3D conformal radiotherapy (3DCRT), giving special consideration to the influence of patient- and treatment-related parameters on side effects. Materials and methods Patients with cervical cancer stage I–IVA underwent radiotherapy alone or chemoradiotherapy using 3DCRT (n = 75) or VMAT (n = 30). Survival endpoints were overall survival, progression-free survival, and locoregional control. The National Cancer Institute Common Terminology Criteria for Adverse Events and the Late Effects of Normal Tissues criteria were used for toxicity assessment. Toxicity and patient- and treatment-related parameters were included in a multivariable model. Results There were no differences in survival rates between treatment groups. VMAT significantly reduced late small bowel toxicity (OR = 0.10, p = 0.03). Additionally, VMAT was associated with an increased risk of acute urinary toxicity (OR = 2.94, p = 0.01). A low body mass index (BMI; OR = 2.46, p = 0.03) and overall acute toxicity ≥grade 2 (OR = 4.17, p &lt; 0.01) were associated with increased overall late toxicity. Conclusion We demonstrated significant reduction of late small bowel toxicity with VMAT treatment, an improvement in long-term morbidity is conceivable. VMAT-treated patients experienced acute urinary toxicity more frequently. Further analysis of patient- and treatment-related parameters indicates that the close monitoring of patients with low BMI and of patients who experienced relevant acute toxicity during follow-up care could improve late toxicity profiles.

Early morbidity and dose–volume effects in definitive radiochemotherapy for locally advanced cervical cancer: a prospective cohort study covering modern treatment techniques

Abstract Purpose Predicting morbidity for patients with locally advanced cervix cancer after external beam radiotherapy (EBRT) based on dose–volume parameters remains an unresolved issue in definitive radiochemotherapy. The aim of this prospective study was to correlate patient characteristics and dose–volume parameters to various early morbidity endpoints for different EBRT techniques, including volumetric modulated arc therapy (VMAT) and adaptive radiotherapy (ART). Methods and materials The study population consisted of 48 patients diagnosed with locally advanced cervix cancer, treated with definitive radiochemotherapy including image-guided adaptive brachytherapy (IGABT). Multiple questionnaires (CTCAE 4.03, QLQ-C30 and EORTC QLQ-CX24) were assessed prospectively for patients treated with different EBRT techniques, including online adaptive VMAT. Contouring and treatment planning was based on the EMBRACE protocols. Acute toxicity, classified as general, gastrointestinal (GI) or genitourinary (GU) and their corresponding dose–volume histograms (DVHs) were first correlated by applying least absolute shrinkage and selection operator (LASSO) and subsequently evaluated by multiple logistic binomial regression. Results The treated EBRT volumes varied for the different techniques with ~2500 cm3 for 3D conformal radiotherapy (3D-CRT), ~2000 cm3 for EMBRACE‑I VMAT, and ~1800 cm3 for EMBRACE-II VMAT and ART. In general, a worsening of symptoms during the first 5 treatment weeks and recovery afterwards was observed. Dose–volume parameters significantly correlating with stool urgency, rectal and urinary incontinence were as follows: bowel V40Gy &lt; 250 cm3, rectum V40Gy &lt; 80% and bladder V40Gy &lt; 80–90%. Conclusion This prospective study demonstrated the impact of EBRT treatment techniques in combination with chemotherapy on early morbidity. Dose–volume effects for dysuria, urinary incontinence, stool urgency, diarrhea, rectal bleeding, rectal incontinence and weight loss were found.

Radiochemotherapy and interstitial brachytherapy for cervical cancer: clinical results and patient-reported outcome measures

Abstract Objective To evaluate clinical results and long-term patient-reported outcome measures (PROMs) on quality of life in cervical cancer patients following radiochemotherapy (RCT) and brachytherapy (BT) as definitive treatment. Materials and methods Between 2003 and 2023, a total of 132 patients with advanced cervical cancer were evaluated for possible treatment. Patients treated by postoperative RCT, palliative radiotherapy, and those treated for recurrent disease were excluded. Thus, 46 patients receiving standard RCT and BT as their curative treatment were included in this study. PROMs were assessed prospectively by patients’ self-completion of the EORTC-QLQ-C30 and EORTC-QLQ-CX24 questionnaires. Results Five-year overall survival (OS), distant metastases-free survival (DMFS), and pelvic tumor-free survival rates (PTFS) were 53%, 54%, and 83%, respectively. A significant impact on OS was seen for FIGO (International Federation of Gynecologic Oncology) stage (IIB–IIIA: 79% vs. IIIB–IVA: 33%, p = 0.015), for overall treatment time (OTT; 50–65 d: 64% vs. &gt; 65 d: 38%, p = 0.004), and for rectal D2cc (≤ 73 Gy: 50% vs. &gt; 73 Gy: 38%, p = 0.046). The identical parameters were significantly associated with DMFS (FIGO stage: p = 0.012, OTT: p = 0.008, D2cc: p = 0.024). No parameters with a significant influence on PTFS were seen. In multivariate analysis, an impact of FIGO stage on OS (p = 0.05) and DMFS (p = 0.014) was detected, and of rectal D2cc on DMFS (p = 0.031). The overall QoL score was 63/100. Cognitive function was the least impaired (84/100), while role functioning was the worst (67/100). On the symptom scale, insomnia (46/100), fatigue (41/100), dyspnea (32/100), pain (26/100), and financial difficulties (25/100) were scored the worst. According to EORTC-QLQ-CX24, peripheral neuropathy (36/100) and lymphedema (32/100) occurred most frequently. Impaired sexual/vaginal functioning (32/100) and body image (22/100) were also frequently recorded. Conclusion In patients with advanced cervical cancer, a combination of RCT and BT remains an excellent treatment option. In terms of patient-reported long-term quality of life, specific support is needed to alleviate symptoms including lymphedema, peripheral neuropathy, and impaired sexual activity.

Transrectal ultrasound for intraoperative interstitial needle guidance in cervical cancer brachytherapy

Abstract Objective This study aimed to prospectively assess the visibility of interstitial needles on transrectal ultrasound (TRUS) in cervical cancer brachytherapy patients and evaluate its impact on implant and treatment plan quality. Material and methods TRUS was utilized during and after applicator insertion, with each needle’s visibility documented through axial images at the high-risk clinical target volume’s largest diameter. Needle visibility on TRUS was scored from 0 (no visibility) to 3 (excellent discrimination, margins distinct). Quantitative assessment involved measuring the distance between tandem and each needle on TRUS and comparing it to respective magnetic resonance imaging (MRI) measurements. Expected treatment plan quality based on TRUS images was rated from 1 (meeting all planning objectives) to 4 (violation of High-risk clinical target volume (CTVHR) and/or organ at risk (OAR) hard constraints) and compared to the final MRI-based plan. Results Analysis included 23 patients with local FIGO stage IB2-IVA, comprising 41 applications with a total of 230 needles. A high visibility rate of 99.1% (228/230 needles) was observed, with a mean visibility score of 2.5 ± 0.7 for visible needles. The maximum and mean difference between MRI and TRUS measurements were 8 mm and –0.1 ± 1.6 mm, respectively, with &gt; 3 mm discrepancies in 3.5% of needles. Expected treatment plan quality after TRUS assessment exactly aligned with the final MRI plan in 28 out of 41 applications with only minor deviations in all other cases. Conclusion Real-time TRUS-guided interstitial needle placement yielded high-quality implants, thanks to excellent needle visibility during insertion. This supports the potential of TRUS-guided brachytherapy as a promising modality for gynecological indications.

Efficient workflow and clinical validation of in-house 3D-printed vaginal cylinders for high-dose-rate brachytherapy for gynecologic malignancies

This study developed an efficient methodology for in-house 3D-printed vaginal cylinders for gynecologic tumor treatment by evaluating their radiation attenuation, geometric accuracy, and efficacy. Ultimately, we aim to establish a simple, cost-effective approach that facilitates broad clinical adoption. Patient-specific vaginal cylinders were designed based on anatomical contours from the treatment planning system (TPS) using CAD software. The process was optimized to minimize manpower and time costs. Radiation attenuation of the 3D printer material was compared with that of water using the Monte Carlo method. Geometric accuracy was automatically analyzed via an in-house MATLAB program. Efficacy was assessed in cases of postoperative vaginal stump recurrence and vaginal cancer with paravaginal invasion. The tumor shape, delineated by TPS, was imported into CAD software, and the catheter pathway model, designed via subtraction processing, was placed at the optimal position and angle. The design process took approximately 15 min, and the entire workflow was completed within a week, demonstrating its practicality for clinical use. The radiation attenuation error was < 3% compared with water, and the geometric accuracy error was < 0.2 mm. The patient-specific vaginal cylinder provided a favorable dose distribution and was effective in complex cases. A feasible workflow was established, allowing in-house design and manufacturing with reduced manpower and time costs. With no material or processing issues, this approach is safe, practical, and promising for widespread adoption in personalized brachytherapy.

Long-term results of robotic radiosurgery for non brachytherapy patients with cervical cancer

Abstract Background Consolidation brachytherapy is a critical treatment component for cervical cancer patients undergoing primary chemoradiation. Some patients are unsuitable for brachytherapy for a variety of reasons. The use of alternatives (LINAC-based stereotactic radiosurgery or external beam boosts) compromise oncologic results in cervical cancer patients. Thus, we evaluated the value of brachytherapy-like doses prescriptions using robotic radiosurgery (CyberKnife®, CR, Acuuray, Sunnyvale, CA, USA). Methods From 06/2011 to 06/2015, 31 patients (median age 53 years; range 30–77 years) with histologically proven FIGO stages IB-IVB cervical cancer underwent primary chemoradiation. All patients were either not suitable for intracervical brachytherapy for a variety of reasons or refused the brachytherapy. To achieve an adequate dose within the tumor, a CK boost was applied after fiducial implantation. In 29 patients, a dose of either five times 6 Gy or five times 5 Gy was prescribed to the target volume. Two patients received three times 5 Gy. The target dose was prescribed to the 70% isodose. Treatment toxicity was documented once weekly regarding vaginal mucositis, bladder, and bowel irritation according to CTCAE v. 4.03. If possible 3 months after completion of treatment intracervical curettage was performed to exclude residual tumor and the patients were followed up clinically. Sparing of organs at risk (OAR) and outcome in terms of local control (LC), overall survival (OS), and progression-free survival (PFS) were assessed. Results Of the 31 patients, 30 have completed CK boost therapy. The median follow-up time was 40 months (range 5–84 months). General treatment tolerability was good. Except for 1 patient, who had diarrhea grade 3, no treatment related side effects above grade 2 were reported. Sparing of OAR was excellent. The 1‑, 3‑, and 5‑year OS rates were 89, 60, and 57% respectively across all stages. Seven patients showed progression (28%), only two of them with local relapse (8%), resulting in an LC rate of 92% after 3 and 5 years. Mean PFS was 41 months (range 2–84 months). Patients with local recurrence had PFS of 5 and 8 months. Five patients developed distant metastases. Fifteen patients (48%) underwent intracervical curettage 3 months after completion of treatment of which 14 (93%) had complete pathologic response. Conclusion Brachytherapy remains the standard of care for patients diagnosed with cervical cancer and indication for primary chemoradiation. In terms of local control, CyberKnife®-based boost concepts provide excellent local control. It can be an alternative for patients who cannot receive adequate brachytherapy. Distant relapse still remains a challenge in this context.

Influence of chemoradiation on the immune microenvironment of cervical cancer patients

Abstract Purpose Cervical cancer remains a leading cause of cancer death in women. While immunotherapy has shown great success in combating cancer, the value of immunotherapy in cervical cancer is still only beginning to be explored. Thus, we performed a prospective analysis of patient blood and tumor samples at the beginning and end of conventional chemoradiation to assess changes in the immune cell and immunoreceptor compartments, and investigate if and when the addition of immunotherapy could be beneficial. Methods Patients with FIGO II–III cervical cancer receiving standard chemoradiation between January 2020 and December 2021 were included. We collected tumor and blood samples from patients before and at the end of therapy and analyzed immune cell composition and immune checkpoint receptor expression on both immune and tumor cells using multicolor flow cytometry. Results In all, 34 patients were eligible in the study period; 22 could be included and analyzed in this study. We found that chemoradiation significantly reduces T cell numbers in both tumors and blood, but increases macrophage and neutrophil numbers in tumors. Furthermore, we found that the percentage of immune checkpoint receptor PD‑1 and TIGIT-expressing cells in tumors was significantly reduced at the end of therapy and that CD4 and CD8 memory T cell populations were altered by chemoradiation. In addition, we observed that while PD-L1 expression intensity was upregulated by chemoradiation on blood CD8 cells, PD-L1 expression frequency and the expression intensity of antigen-presenting molecule MHC‑I were significantly reduced on tumor cells. Conclusion Our data demonstrate that chemoradiation significantly alters the immune cell composition of human cervical tumors and the expression of immune checkpoint receptors on both lymphocytes and tumor cells. As our results reveal that the percentage of PD‑1+ CD8 cells in the tumor as well as the frequency of PD-L1-expressing tumor cells were reduced at the end of therapy, neoadjuvant or simultaneous anti-PD‑1 or anti-PD-L1 treatment might provide better treatment efficiency in upcoming clinical studies.

Non-endometrioid endometrial cancer: analysis of recurrence pattern and identification of prognostic and treatment factors affecting recurrence and survival

We investigated the characteristics of recurrence pattern and survival of patients with non-endometrioid endometrial cancer (NEEC) and attempted to identify prognostic and treatment factors affecting disease-free survival (DFS) and overall survival (OS) of these patients. Fifty-seven patients with histologically confirmed International Federation of Gynecology and Obstetrics (FIGO) stage IA-IVA NEEC from February 2003 to December 2021 were retrospectively analyzed. The 5‑year DFS and OS rates of the total cohort were 50.6% and 56.1%, respectively. Recurrence occurred in 28 patients (49.1%) during follow-up, and the most common recurrence pattern was distant metastasis (DM; 78.6% of total recurrences). The occurrence of relapse significantly reduced 5‑year OS (recurrence group vs. non-recurrence group: 12.5% vs. 100%; p < 0.001). In univariate analysis, adjuvant radiotherapy (RT) group showed significantly higher 5‑year DFS (56.7% vs. 37.9%; p = 0.04), local recurrence-free survival (91.6% vs. 50.5%; p = 0.01), and regional recurrence-free survival (88.2% vs. 56.5%; p < 0.01) than the non-RT group. In multivariate analysis, advanced FIGO stage was identified as a negative prognostic factor for DFS and OS. Lymphovascular space invasion (LVSI) and adjuvant RT were independent prognostic factors for DFS. The most common recurrence pattern observed in patients with NEEC was DM. FIGO stage and LVSI were identified as prognostic factors for survival, and RT was identified as a therapeutic modality that could increase DFS. To improve the OS of patients with NEEC, the addition of effective chemotherapy that can reduce DM may be important.

Publisher

Springer Science and Business Media LLC

ISSN

0179-7158