The clinical practice and dosimetric outcome of the manual adaptive planning during definitive radiotherapy for cervical cancer.

PROPOSE: To evaluate the advantage of the manual adaptive plans comparing to the scheduled plans, and explored clinical factors predicting patients suitable for adaptive strategy. METHODS AND MATERIALS: Eighty two patients with weekly online cone-beam computed tomography (CBCT) were enrolled. The re-CT simulation was performed after 15 fractions and a manual adaptive plan was developed if a significant deviation of the planning target volume (PTV) was found. To evaluate the dosimetric benefit, D98, homogeneity index (HI) and conformity index (CI) for the planning target volume (PTV), as well as D2cc of the bowel, bladder, sigmoid and rectum were compared between manual adaptive plans and scheduled ones. The clinical factors influencing target motion during radiotherapy were analyzed by chi-square test and logistic regression analysis. RESULTS: The CI and HI of the manual adaptive plans were significantly superior to the scheduled ones (P = 0.0002, 0.003, respectively), demonstrating a better dose coverage of the target volume. Compared to the scheduled plans, D98 of the manual adaptive plans increased by 3.3% (P = 0.0002), the average of D2cc to the rectum, bladder decreased 0.358 Gy (P = 0.000034) and 0.240 Gy (P = 0.03), respectively. In addition, the chi-square test demonstrated that age, primary tumor volume, and parametrial infiltration were the clinical factors influencing target motion during radiotherapy. Multivariate analysis further identified the large tumor volume (≥ 50cm3, OR = 3.254, P = 0.039) and parametrial infiltration (OR = 3.376, P = 0.018) as the independent risk factors. CONCLUSION: We found the most significant organ motion happened after 15 fractions during treatment. The manual adaptive plans improved the dose coverage and decreased the OAR doses. Patients with bulky mass or with parametrial infiltration were highly suggested to adaptive strategy during definitive radiotherapy due to the significant organ motion.

Efficacy and safety of different chemotherapy regimens concurrent with radiotherapy in the treatment of locally advanced cervical cancer.

BACKGROUND: Evaluate the efficacy and safety of different chemotherapy regimens concurrent with radiotherapy in treating locally advanced cervical cancer (LACC). METHODS: Retrospective data was collected from LACC patients who were treated at our institution. These patients were categorized into three groups: the single-agent cisplatin (DDP) chemoradiotherapy group, the paclitaxel plus cisplatin (TP) chemoradiotherapy group, and the nanoparticle albumin-bound (nab-) paclitaxel combined with cisplatin (nPP) chemoradiotherapy group. The primary endpoints were overall survival (OS) and progression-free survival (PFS) and the secondary endpoints were objective response rate (ORR) and incidence of adverse events (AEs). RESULTS: A total of 124 patients were enrolled (32 in the DDP group, 41 in the TP group, and 51 in the nPP group). There were differences in OS (P = 0.041, HR 0.527, 95% CI 0.314-0.884) and PFS (P = 0.003, HR 0.517, 95% CI 0.343-0.779) between the three groups. Notably, the 2-year OS rate was significantly higher in the nPP group compared to the DDP group (92.2% vs. 85.4%, P = 0.012). The 2-year PFS rates showed a marked increase in the TP group (78.0% vs. 59.4%, P = 0.048) and the nPP group (88.2% vs. 59.4%, P = 0.001) relative to the DPP group, with multiple comparisons indicating that the 2-year PFS rate was significantly superior in the nPP group versus the DDP group (88.2% vs. 59.4%, P = 0.001). Moreover, the ORR was also significantly higher in the nPP group than in the DDP group (P = 0.013); and no statistically significant differences were found in the incidence of AEs among the groups (P > 0.05). CONCLUSIONS: In LACC treatment, the two cisplatin-based doublet chemotherapy regimens are associated with better outcomes, with the nab-paclitaxel plus cisplatin regimen showing better efficacy than the paclitaxel plus cisplatin regimen. Furthermore, the AEs associated with these regimens were deemed tolerable. These findings could provide a reference for the clinical treatment of LACC. However, further prospective studies are needed to verify it.

Clinical Outcomes and Dosimetric Evaluationof Interstitial Brachytherapyin Gynecological Malignancies.

BACKGROUND: In management of Carcinoma Cervix, Brachytherapy plays a crucial role. Most commonly used technique is Intracavitary Brachytherapy (ICBT). In cases where ICBT is not technically feasible or it may result in suboptimal dose distribution, Interstitial Brachytherapy (ISBT) is recommended. With this study we wanted to study the clinical outcome and dosimetric details of interstitial brachytherapy in gynecological cancers. MATERIALS & METHODS: We analysed clinicaloutcome and dosimetric details of interstitial brachytherapy (ISBT) done for gynecological malignancies in our institute during the period 1st January 2013 to 31st December 2020. RESULTS: Total of 42 interstitial brachytherapy (ISBT) details were analysed.37 patients had Carcinoma Cervix and 5 patients had Carcinoma Vagina. In the majority of the patients, ISBT dosage schedule was three fractions 7Gy each. D2cc to rectum, bladder, sigmoid and bowel were 4.88 Gy, 5.62 Gy, 3.57 Gy and 2.47 Gy respectively. Mean CTV volume was 129.89 cc. EQD2 dose to CTV combining EBRT and ISBT dose was 85.88 Gy. D90 and D100 to CTV from ISBT were 111.96% and 68.21 % of prescribed dose respectively. Grade III/IV toxicities were seen in 5 (12%) patients. Local control rates at 1year &2 years were 88% & 85.7% respectively. DFS at 1 year, 2 years and 3 years were 80.7%, 72.3% and 65.7% respectively. OS at 1year, 2 years, 4 years and 5 years were 92.5%, 65.5%, 59.5% and 42.3% respectively. CONCLUSION: 3D imagebased dosimetry with CT based planning using MUPIT implant is a feasible option for gynecological malignancies warranting interstitial brachytherapy. In view of good clinical outcomes in terms of toxicity profile, Local control, DFS and OS with acceptable GEC-ESTRO dosimetric data, we recommend routine use interstitial brachytherapy if facilities are available and in clinical situations were ISBT is indicated.

[Brachytherapy : a crucial part of locally advanced cervical cancer treatment]. / La curiethérapie : un atout majeur dans le traitement du cancer du col de l'utérus localement avancé.

Cervical cancer is the 4th most diagnosed cancer in women. At a locally advanced stage, standard treatment combines chemotherapy, radiotherapy and a brachytherapy boost. Brachytherapy is a radiotherapy modality, often unknown, which allows the delivery of a very targeted high dose because it's given directly in contact with the tumor. This technique has proven its effectiveness in the treatment of locally advanced cervical cancer. It represents a major advantage because, despite technical advances, there is currently no alternative yielding equivalent results.

Le cancer du col utérin est le 4ème cancer féminin le plus diagnostiqué. à un stade localement avancé, la prise en charge standard relève d'un traitement associant de la chimiothérapie, de la radiothérapie et une curiethérapie de clôture. La curiethérapie est une modalité de radiothérapie, souvent méconnue du grand public, qui permet de délivrer une dose élevée de façon très ciblée, car celle-ci est donnée directement au contact de la tumeur. Cette technique a prouvé son efficacité et son caractère indispensable dans le traitement du cancer du col utérin localement avancé. Elle représente un atout majeur car, malgré l'évolution des techniques de radiothérapie externe plus modernes, il n'y a, à ce jour, aucune alternative équivalente.

Effective timing of hyaluronate gel injection in image-guided adaptive brachytherapy for uterine cervical cancer: a proposal of the 'adjusted dose score'.

Hyaluronate gel injection (HGI) in the rectovaginal septum and vesicovaginal septum is effective in the setting of high-dose-rate image-guided adaptive brachytherapy (IGABT) for cervical cancer. We aimed to retrospectively investigate optimal conditions for HGI to achieve optimal dose distribution with a minimum number of HGI. We classified 50 IGABT plans of 13 patients with cervical cancer who received IGABT both with and without HGI in the rectovaginal septum and vesicovaginal septum into the following two groups: plan with (number of plans = 32) and plan without (number of plans = 18) HGI. The irradiation dose parameters of high-risk clinical target volume (CTVHR) and organs at risk per fraction were compared between these groups. We also developed the adjusted dose score (ADS), reflecting the overall irradiation dose status for four organs at risk and CTVHR in one IGABT plan and investigated its utility in determining the application of HGI. HGI reduced the maximum dose to the most exposed 2.0 cm3 (D2.0 cm3) of the bladder while increasing the minimum dose covering 90% of CTVHR and the percentage of CTVHR receiving 100% of the prescription dose in one IGABT plan without causing any associated complications. An ADS of ≥2.60 was the optimum cut-off value to decide whether to perform HGI. In conclusion, HGI is a useful procedure for improving target dose distribution while reducing D2.0 cm3 in the bladder in a single IGABT plan. The ADS can serve as a useful indicator for the implementation of HGI.

Insights into pelvic insufficiency fracture following pelvic radiotherapy for cervical cancer: a comparative review.

BACKGROUND: Radiotherapy (RT)-induced pelvic insufficiency fractures (PIF) are prevalent in patients with cervical cancer. Inconclusive studies on PIF after cervical irradiation create uncertainty. This review examined PIF after RT in cervical patients, including its pathobiology, likely locations of fractures, incidence, clinical symptoms, and predisposing factors. We further discussed study limitations and therapeutic possibilities of PIF. METHODS: The following online resources were searched for relevant articles: Google Scholar and PubMed. The keywords 'pelvic insufficiency fractures', 'cervical carcinoma' and 'cervical cancer', as well as 'chemoradiotherapy', 'chemoradiation', and 'radiotherapy', were some of the terms that were used during the search. RESULTS: Patients with PIF report pelvic pain after radiation treatment for cervical cancer; the incidence of PIF ranges from 1.7 to 45.2%. Evidence also supports that among all patients treated with pelvic radiation, those who experienced pelvic insufficiency fractures invariably had at least one sacral fracture, making it the most frequently fractured bone in the body. Menopausal status, weight, BMI, age, and treatments and diagnosis modalities can influence PIF during radiotherapy. CONCLUSIONS: In conclusion, our comparative review of the literature highlights significant heterogeneity in various aspects of PIF following radiation for patients with cervical cancer. This diversity encompasses prevalence rates, associated risk factors, symptoms, severity, diagnosis methods, preventive interventions, and follow-up periods. Such diversity underscores the complexity of PIF in this population and emphasizes the critical need for further research to elucidate optimal management strategies and improve patient outcomes.

A novel nomogram based on inflammation biomarkers for predicting radiation cystitis in patients with local advanced cervical cancer.

BACKGROUNDS: Platelet-to-albumin ratio (PAR) is a new systemic inflammatory prognostic indicator associated with many inflammatory diseases. However, its role in radiation cystitis (RC) is obscure. This study aimed to explore whether PAR could be used as an effective parameter for predicting the RC risk in local advanced cervical cancer (CC) treated with radiotherapy. METHODS: A total of 319 local advanced CC patients who received radical radiotherapy at Fujian Cancer Hospital were enrolled between December 2018 and January 2021. Demographics and clinical parameters were retrospectively analyzed. Univariate and multivariate analyses were used to identify the risk factors for RC. Backward and stepwise regression was applied to construct two monograms-one with primary significant factors and the other with extra inflammatory biomarkers. A DeLong test was applied to compare the prediction abilities of two nomograms. Calibration curves and decision curve analysis (DCA) evaluated its prediction consistency, discrimination ability, and clinical net benefit. RESULTS: Univariate analysis showed that age, tumor size, stage, total radiation dose, pelvic radiation dose, Systemic Immune-Inflammation Index (SII), platelet-to-lymphocyte ratio (PLR), and PAR were significantly associated with RC occurrence (all p < 0.05). Multivariate analyses indicated that age, tumor size, stage, total radiation dose, and PAR were independent factors (all p < 0.05). Then, the area under curve (AUC) value of the nomogramSII+PAR was higher (AUC = 0.774) compared to that of the baseline nomogram (AUC = 0.726) (pDelong = 0.02). Also, the five-cross validation confirmed the stability of the nomogramSII+PAR. Moreover, the calibration curve and DCA exhibited the nomograms' good prediction consistency and clinical practicability. CONCLUSIONS: PAR and SII could be valued for CC patients who are treated with radiation therapy. The nomogram based on PAR and SII could stratify patients who need extra intervention and nursing care to prevent bladder radiation damage and improve patients' quality of life.

Comparative analysis of treatment decision-making in patients with localized prostate and cervical cancer: what influences receiving surgery or radiotherapy?

PURPOSE: This study focused on identifying the factors influencing the decision-making process in patients with localized prostate and cervical cancer in Japan and specifically examining the choice between surgery and radiotherapy. METHODS: Patients with specific cancer stages registered with a healthcare research company for whom radical surgery or radiotherapy was equally effective and recommended participated in this cross-sectional online survey. RESULTS: The responses of 206 and 231 patients with prostate and cervical cancer, respectively, revealed that both groups relied heavily on the physicians' recommendations (prostate: odds ratio (OR) = 40.3, p < 0.001; cervical: OR = 5.59, p < 0.001) and their impression of radiotherapy (prostate: OR = 9.22, p < 0.001; cervical: OR = 2.31, p < 0.001). Factors such as hypertension (OR = 6.48, p < 0.05), diabetes mellitus (OR = 9.68, p < 0.05), employment status (OR = 0.08, p < 0.01), and impressions of surgery (OR = 0.14, p < 0.01) also played a significant role in patients with prostate cancer. In contrast, the specialty of the physician (OR = 4.55, p < 0.05) proposing the treatment influenced the decision-making process of patients with cervical cancer. Information sources varied between the two groups: patients with prostate cancer were more inclined towards printed materials, whereas patients with cervical cancer were more inclined towards interpersonal relationships. CONCLUSION: Although several limitations, such as the sample and recall bias, were noted, this study emphasizes the role of psychosocial factors in the decision-making process and the requirement for tailored information sources.

Comparative analysis of simultaneous integrated boost and sequential boost radiotherapy in node-positive cervical cancer: dosimetric and radiobiological considerations.

For locally advanced cervical cancer, the standard therapeutic approach involves concomitant chemoradiation therapy, supplemented by a brachytherapy boost. Moreover, an external beam radiotherapy (RT) boost should be considered for treating gross lymph node (LN) volumes. Two boost approaches exist with Volumetric Intensity Modulated Arc Therapy (VMAT): Sequential (SEQ) and Simultaneous Integrated Boost (SIB). This study undertakes a comprehensive dosimetric and radiobiological comparison between these two boost strategies. The study encompassed ten patients who underwent RT for cervical cancer with node-positive disease. Two sets of treatment plans were generated for each patient: SIB-VMAT and SEQ-VMAT. Dosimetric as well as radiobiological parameters including tumour control probability (TCP) and normal tissue complication probability (NTCP) were compared. Both techniques were analyzed for two different levels of LN involvement - only pelvic LNs and pelvic with para-aortic LNs. Statistical analysis was performed using SPSS software version 25.0. SIB-VMAT exhibited superior target coverage, yielding improved doses to the planning target volume (PTV) and gross tumour volume (GTV). Notably, SIB-VMAT plans displayed markedly superior dose conformity. While SEQ-VMAT displayed favorable organ sparing for femoral heads, SIB-VMAT appeared as the more efficient approach for mitigating bladder and bowel doses. TCP was significantly higher with SIB-VMAT, suggesting a higher likelihood of successful tumour control. Conversely, no statistically significant difference in NTCP was observed between the two techniques. This study's findings underscore the advantages of SIB-VMAT over SEQ-VMAT in terms of improved target coverage, dose conformity, and tumour control probability. In particular, SIB-VMAT demonstrated potential benefits for cases involving para-aortic nodes. It is concluded that SIB-VMAT should be the preferred approach in all cases of locally advanced cervical cancer.

Carbon ion radiotherapy for mesonephric adenocarcinoma of the uterine cervix: a case report.

BACKGROUND: Mesonephric adenocarcinoma is an extremely rare subtype of uterine cervical cancer that is associated with a poor prognosis and for which a standardized treatment protocol has not been established. Carbon ion radiotherapy (CIRT) is an emerging radiotherapy modality that has been shown to have a favorable anti-tumor effect, even for tumors resistant to conventional photon radiotherapy or chemotherapy. However, there is no report on CIRT outcomes for mesonephric adenocarcinoma of the uterine cervix. CASE PRESENTATION: We treated a 47-year-old Japanese woman with mesonephric adenocarcinoma of the uterine cervix (T2bN0M0 and stage IIB according to the 7th edition of the Union for International Cancer Control and International Federation of Gynecology and Obstetrics, respectively) with CIRT combined with brachytherapy and concurrent chemotherapy. CIRT consisted of whole pelvic irradiation and boost irradiation to the gross tumor; 36.0 Gy (relative biological effectiveness [RBE]) in 12 fractions and 19.2 Gy (RBE) in 4 fractions, respectively, performed once a day, four times per week. Computed tomography-based image-guided adaptive brachytherapy was performed after completion of CIRT, for which the D90 (i.e., the dose prescribed to 90% of the target volume) for the high-risk clinical target volume was 20.4 Gy in a total of 3 sessions in 2 weeks. A weekly cisplatin (40 mg/m2) dose was administered concomitantly with the radiotherapy for a total of five courses. From 4 months post-CIRT, the patient developed metastasis of the lung, with a total of 10 lung metastases over 70 months; these lesions were treated on each occasion by photon stereotactic body radiotherapy and/or systemic therapy. At 8 years from initial treatment (i.e., 2 years after the last treatment), the patient is alive without any evidence of recurrence and maintains a high quality of life. CONCLUSIONS: This is the first report of CIRT for treatment of mesonephric adenocarcinoma of the uterine cervix. The present case indicates the potential efficacy of CIRT in combination with brachytherapy for treatment of this disease.

Intestinal microecological transplantation for a patient with chronic radiation enteritis: A case report.

BACKGROUND: The gut microbiota is strongly associated with radiation-induced gut damage. This study aimed to assess the effectiveness and safety of intestinal microecological transplantation for treating patients with chronic radiation enteritis. CASE SUMMARY: A 64-year-old female with cervical cancer developed abdominal pain, diarrhea, and blood in the stool 1 year after radiotherapy. An electronic colonoscopy was performed to diagnose chronic radiation enteritis. Two courses of intestinal microecological transplantation and full-length 16S rRNA microbiological analysis were performed. The patient experienced short- and long-term relief from symptoms without adverse effects. Whole 16S rRNA sequencing revealed significant differences in the intestinal flora's composition between patient and healthy donors. Pathogenic bacteria, such as Escherichia fergusonii and Romboutsia timonensis, were more in the patient. Beneficial bacteria such as Faecalibacterium prausnitzii, Fusicatenibacter saccharivorans, Ruminococcus bromii, and Bifidobacterium longum were more in the healthy donors. Intestinal microbiota transplantation resulted in a significant change in the patient's intestinal flora composition. The composition converged with the donor's flora, with an increase in core beneficial intestinal bacteria, such as Eubacterium rectale, and a decrease in pathogenic bacteria. Changes in the intestinal flora corresponded with the patients' alleviating clinical symptoms. CONCLUSION: Intestinal microecological transplantation is an effective treatment for relieving the clinical symptoms of chronic radiation enteritis by altering the composition of the intestinal flora. This study provides a new approach for treating patients with chronic radiation enteritis.

Risk Prediction Model for Radiation-induced Dermatitis in Patients with Cervical Carcinoma Undergoing Chemoradiotherapy.

PURPOSE: Radiation-induced dermatitis (RD) is a common side-effect of therapeutic ionizing radiation that can severely affect patient quality of life. This study aimed to develop a risk prediction model for the occurrence of RD in patients with cervical carcinoma undergoing chemoradiotherapy using electronic medical records (EMRs). METHODS: Using EMRs, the clinical data of patients who underwent simultaneous radiotherapy and chemotherapy at a tertiary cancer hospital between 2017 and 2022 were retrospectively collected, and the patients were divided into two groups: a training group and a validation group. A predictive model was constructed to predict the development of RD in patients who underwent concurrent radiotherapy and chemotherapy for cervical cancer. Finally, the model's efficacy was validated using a receiver operating characteristic curve. RESULTS: The incidence of radiation dermatitis was 89.5% (560/626) in the entire cohort, 88.6% (388/438) in the training group, and 91.5% (172/188) in the experimental group. The nomogram was established based on the following factors: age, the days between the beginning and conclusion of radiotherapy, the serum albumin after chemoradiotherapy, the use of single or multiple drugs for concurrent chemotherapy, and the total dose of afterloading radiotherapy. Internal and external verification indicated that the model had good discriminatory ability. Overall, the model achieved an area under the receiver operating characteristic curve of .66. CONCLUSIONS: The risk of RD in patients with cervical carcinoma undergoing chemoradiotherapy is high. A risk prediction model can be developed for RD in cervical carcinoma patients undergoing chemoradiotherapy, based on over 5 years of EMR data from a tertiary cancer hospital.

Hyperpolarized [1-13C]-pyruvate MRS evaluates immune potential and predicts response to radiotherapy in cervical cancer.

BACKGROUND: Monitoring pyruvate metabolism in the spleen is important for assessing immune activity and achieving successful radiotherapy for cervical cancer due to the significance of the abscopal effect. We aimed to explore the feasibility of utilizing hyperpolarized (HP) [1-13C]-pyruvate magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) to evaluate pyruvate metabolism in the human spleen, with the aim of identifying potential candidates for radiotherapy in cervical cancer. METHODS: This prospective study recruited six female patients with cervical cancer (median age 55 years; range 39-60) evaluated using HP [1-13C]-pyruvate MRI/MRS at baseline and 2 weeks after radiotherapy. Proton (1H) diffusion-weighted MRI was performed in parallel to estimate splenic cellularity. The primary outcome was defined as tumor response to radiotherapy. The Student t-test was used for comparing 13C data between the groups. RESULTS: The splenic HP [1-13C]-lactate-to-total carbon (tC) ratio was 5.6-fold lower in the responders than in the non-responders at baseline (p = 0.009). The splenic [1-13C]-lactate-to-tC ratio revealed a 1.7-fold increase (p = 0.415) and the splenic [1-13C]-alanine-to-tC ratio revealed a 1.8-fold increase after radiotherapy (p = 0.482). The blood leukocyte differential count revealed an increased proportion of neutrophils two weeks following treatment, indicating enhanced immune activity (p = 0.013). The splenic apparent diffusion coefficient values between the groups were not significantly different. CONCLUSIONS: This exploratory study revealed the feasibility of HP [1-13C]-pyruvate MRS of the spleen for evaluating baseline immune potential, which was associated with clinical outcomes of cervical cancer after radiotherapy. TRIAL REGISTRATION: ClinicalTrials.gov NCT04951921 , registered 7 July 2021. RELEVANCE STATEMENT: This prospective study revealed the feasibility of using HP 13C MRI/MRS for assessing pyruvate metabolism of the spleen to evaluate the patients' immune potential that is associated with radiotherapeutic clinical outcomes in cervical cancer. KEY POINTS: • Effective radiotherapy induces abscopal effect via altering immune metabolism. • Hyperpolarized 13C MRS evaluates patients' immune potential non-invasively. • Pyruvate-to-lactate conversion in the spleen is elevated following radiotherapy.

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

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.

Effects of bone marrow sparing radiotherapy on acute hematologic toxicity for patients with locoregionally advanced cervical cancer: a prospective phase II randomized controlled study.

OBJECTIVE: To evaluate effects of bone marrow sparing (BMS) radiotherapy on decreasing the incidence of acute hematologic toxicity (HT) for locoregionally advanced cervical cancer (LACC) patients treated by pelvic irradiation. MATERIALS AND METHODS: LACC patients were recruited prospectively from May 2021 to May 2022 at a single center and were evenly randomized into the BMS group and the control group. All patients received pelvic irradiation with concurrent cisplatin (40 mg/m2 weekly), followed by brachytherapy and BM V40 < 25% in the BMS group was additionally prescribed. Acute HT was assessed weekly. Binary logistic regression model and receiver operating characteristic (ROC) curve were used for predictive value analysis. The trial was registered with Chinese clinical trial registry (ChiCTR2200066485). RESULTS: A total of 242 patients were included in the analysis. Baseline demographic, disease and treatment characteristics were balanced between the two groups. In the intention-to-treat population, BMS was associated with a lower incidence of grade ≥ 2 and grade ≥ 3 acute HT, leukopenia and neutropenia s(72.70% v 90.90%, P < 0.001*; 16.50% vs. 65.30%, P < 0.001*; 66.10% vs. 85.10%, P = 0.001*; 13.20% vs. 54.50%, P < 0.001*; 37.20% vs. 66.10%, P < 0.001*; 10.70% vs. 43.80%, P < 0.001*). BMS also resulted in decreased dose delivered to the organs at risk (OARs) including rectum, bladder and left and right femoral head. Univariate and multivariate analyses showed that BM V40 was an independent risk factor for grade ≥ 3 acute HT (odds ratio [OR] = 2.734, 95% confidence interval [CI] = 1.959-3.815, P < 0.001*). Cutoff value was 25.036% and area under the curve (AUC) was 0.786. The nomogram was constructed, which was rigorously evaluated and internally cross-validated, showing good predictive performance. CONCLUSIONS: Receiving BMS pelvic irradiation could reduce the incidence of acute HT in LACC patients, and BM V40 < 25% may be a significant factor in reducing the risks of acute HT.

Exploratory study of using Magnetic resonance Prognostic Imaging markers for Radiotherapy In Cervix cancer (EMPIRIC): a prospective cohort study protocol.

INTRODUCTION: Radical chemoradiotherapy represents the gold standard for locally advanced cervical cancer. However, despite significant progress in improving local tumour control, distant relapse continues to impact overall survival. The development of predictive and prognostic biomarkers is consequently important to risk-stratify patients and identify populations at higher risk of poorer treatment response and survival outcomes. Exploratory study of using Magnetic resonance Prognostic Imaging markers for Radiotherapy In Cervix cancer (EMPIRIC) is a prospective exploratory cohort study, which aims to investigate the role of multiparametric functional MRI (fMRI) using diffusion-weighed imaging (DWI), dynamic contrast-enhanced (DCE) and blood oxygen level-dependent imaging (BOLD) MRI to assess treatment response and predict outcomes in patients undergoing radical chemoradiotherapy for cervical cancer. METHODS AND ANALYSIS: The study aims to recruit 40 patients across a single-centre over 2 years. Patients undergo multiparametric fMRI (DWI, DCE and BOLD-MRI) at three time points: before, during and at the completion of external beam radiotherapy. Tissue and liquid biopsies are collected at diagnosis and post-treatment to identify potential biomarker correlates against fMRI. The primary outcome is to evaluate sensitivity and specificity of quantitative parameters derived from fMRI as predictors of progression-free survival at 2 years following radical chemoradiotherapy for cervical cancer. The secondary outcome is to investigate the roles of fMRI as predictors of overall survival at 2 years and tumour volume reduction across treatment. Statistical analyses using regression models and survival analyses are employed to evaluate the relationships between the derived parameters, treatment response and clinical outcomes. ETHICS AND DISSEMINATION: The EMPIRIC study received ethical approval from the NHS Health Research Authority (HRA) on 14 February 2022 (protocol number RD2021-29). Confidentiality and data protection measures are strictly adhered to throughout the study. The findings of this study will be disseminated through peer-reviewed publications and scientific conferences, aiming to contribute to the growing body of evidence on the use of multiparametric MRI in cervical cancer management. TRIAL REGISTRATION NUMBER: NCT05532930.

Interstitial round needles should not be used for cervical cancer patient treated with intracavitary/ interstitial brachytherapy using a Venezia applicator : a case report.

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.

A Comparative Study of Deep Learning Dose Prediction Models for Cervical Cancer Volumetric Modulated Arc Therapy.

Purpose: Deep learning (DL) is widely used in dose prediction for radiation oncology, multiple DL techniques comparison is often lacking in the literature. To compare the performance of 4 state-of-the-art DL models in predicting the voxel-level dose distribution for cervical cancer volumetric modulated arc therapy (VMAT). Methods and Materials: A total of 261 patients' plans for cervical cancer were retrieved in this retrospective study. A three-channel feature map, consisting of a planning target volume (PTV) mask, organs at risk (OARs) mask, and CT image was fed into the three-dimensional (3D) U-Net and its 3 variants models. The data set was randomly divided into 80% as training-validation and 20% as testing set, respectively. The model performance was evaluated on the 52 testing patients by comparing the generated dose distributions against the clinical approved ground truth (GT) using mean absolute error (MAE), dose map difference (GT-predicted), clinical dosimetric indices, and dice similarity coefficients (DSC). Results: The 3D U-Net and its 3 variants DL models exhibited promising performance with a maximum MAE within the PTV 0.83% ± 0.67% in the UNETR model. The maximum MAE among the OARs is the left femoral head, which reached 6.95% ± 6.55%. For the body, the maximum MAE was observed in UNETR, which is 1.19 ± 0.86%, and the minimum MAE was 0.94 ± 0.85% for 3D U-Net. The average error of the Dmean difference for different OARs is within 2.5 Gy. The average error of V40 difference for the bladder and rectum is about 5%. The mean DSC under different isodose volumes was above 90%. Conclusions: DL models can predict the voxel-level dose distribution accurately for cervical cancer VMAT treatment plans. All models demonstrated almost analogous performance for voxel-wise dose prediction maps. Considering all voxels within the body, 3D U-Net showed the best performance. The state-of-the-art DL models are of great significance for further clinical applications of cervical cancer VMAT.

[Effect of COVID-19 pandemics in treatment of cervical cancer: pre/post study]. / Efecto de COVID-19 en el tratamiento del cáncer cervicouterino: estudio antes/después.

INTRODUCTION: Little evidence exists on the impact of the COVID-19 pandemics on the compliance with cervical cancer treatment. METHODS: We carried out a population-based, before-and-after retrospective cohort study of all cervical cancer patients diagnosed in the Jujuy province public health sector (n=140), Argentina, between 2017 and 2020. Patients diagnosed in 2020 were considered exposed to the COVID-19 pandemic (n=21). We used multivariable logistic regression to assess the relationship between the pandemics and compliance with treatment. We also measured treatment duration for women who were indicated brachytherapy and time to treatment initiation by stage. RESULTS: Compared with women diagnosed in 2017-2019 the odds ratio of non-complying with treatment was 1.77 (95%CI 0.59-5.81; p = 0.32) for women diagnosed during 2020. An increased risk of non-compliance was found in patients with prescribed brachytherapy (OR 4.14. 95%CI 1.95-9.11; p < 0.001). Median treatment duration for women with prescribed brachytherapy was 12.8 and 15.7 weeks in 2017-2019 vs. 2020 (p = 0.33); median time to treatment initiation for women with early-stage disease was 9 and 5 weeks during 2017-2019 and 2020 respectively (p = 0.06), vs 7.2 and 9 weeks in 2017-2019 and 2020 respectively (p = 0.36) for patients with stages IIB+ disease. CONCLUSIONS: Low access to brachytherapy was a major determinant of non-compliance. irrespective of the effect of the pandemics.

Introducción: Hay escasa evidencia sobre el impacto de la pandemia de COVID-19 en el cumplimiento del tratamiento de cáncer cervicouterino. Métodos: Se llevó a cabo un estudio poblacional de cohorte retrospectivo. ­antes/después­ de las pacientes con cáncer cervicouterino diagnosticadas en establecimientos públicos de la provincia de Jujuy (n = 140), entre 2017 y 2020. Las pacientes diagnosticadas en 2020 se consideraron expuestas a la pandemia (n = 21). Utilizamos la regresión logística multivariada para analizar la asociación entre pandemia y cumplimiento del tratamiento de cáncer. Además, se midió la duración del tratamiento en aquellas con indicación de braquiterapia y el tiempo hasta el inicio al tratamiento según estadio. Resultados: Comparadas con las mujeres diagnosticadas en 2017-2019 el odds ratio de incumplimiento del tratamiento fue de 1.77 (IC95% 0.59-5.81; p = 0.32) para las diagnosticadas durante 2020. Se encontró un mayor riesgo de incumplimiento en pacientes con indicación de braquiterapia (OR 4.14; IC 95%:1.95-9.11; p < 0.001). La mediana de duración del tratamiento para aquellas con indicación de braquiterapia fue de 12.8 y 15.7 semanas en 2017-2019 y 2020 respectivamente (p = 0.33). La mediana de tiempo hasta el inicio del tratamiento para pacientes con enfermedad en estadio temprano fue de 9 y 5 semanas durante 2017-2019 y 2020 respectivamente (p = 0.06), versus una mediana de 7.2 y 9 semanas en 2017-2019 y 2020 respectivamente (p=0.36) para las pacientes con enfermedad en estadio IIB+. Conclusiones: El bajo acceso a la braquiterapia fue un factor determinante de incumplimiento de tratamiento de cáncer cervicouterino, independientemente del efecto de la pandemia.

A Comparative Study of Clinical Outcomes in Locally Advanced Cervical Cancer: External Beam Radiotherapy (EBRT) and Sequential High Dose Rate Intracavitary Brachytherapy (HDRICBT) with or without Concurrent Cisplatin on the Day of ICBT Insertion - A Tertiary Care Center Randomized Controlled Trial in India.

OBJECTIVE: The current study aimed to delve into the comparative clinical outcomes between external beam radiation therapy (EBRT) and sequential High Dose Rate Intracavitary Brachytherapy (HDRICBT) with or without concurrent cisplatin administration on the day of intracavitary brachytherapy (ICBT) insertion in women with locally advanced cervical cancer. METHODS: In this study, conducted between January 2017 and July 2018 at a leading institute in India, diagnosed and untreated patients of locally advanced carcinoma cervix were randomized into two groups. Arm 1 received concurrent cisplatin before each course of brachytherapy, while Arm 2 underwent brachytherapy alone. The outcomes were compared in terms of acute and late toxicities, treatment response, and follow-up. Data analysis was performed using SPSS 16, with statistical significance set at p < 0.05. RESULTS: Both study arms showed similar complete response (CR) rates of 73.3%, with no significant advantage of concurrent cisplatin before brachytherapy. However, a noteworthy trend emerged during follow-up. In the concurrent cisplatin group, the CR rate increased from 73.3% post 1 month of brachytherapy to 86.7% at 3 months and 83.3% at 6 months. Contrastingly, the control group showed CR rates of 73.3% post 1 month, 80% at 3 months, and 76.6% at 6 months. While not statistically significant, this observation suggests a possible enhancement in response rates with concurrent cisplatin and ICBT. CONCLUSIONS: Future studies focusing on the optimal drug, dosage, scheduling, and combining cisplatin with other agents are recommended to further explore the potential benefits observed in this study.