Uterine Cervical Cancer Research Articles

PO0259: Treatment Outcomes of a Combination with Intensity-Modulated Radiotherapy and Computed Tomography-Based Image-Guided Brachytherapy for Uterine Cervical Cancer in a Single Japanese Institution

PO0259: Treatment Outcomes of a Combination with Intensity-Modulated Radiotherapy and Computed Tomography-Based Image-Guided Brachytherapy for Uterine Cervical Cancer in a Single Japanese Institution

Influence of COVID-19 on the clinical characteristics of patients with uterine cervical cancer in Japan: A single-center retrospective study.

This study investigated the impact of coronavirus disease 2019 (COVID-19) on the clinical characteristics and interregional movement of patients with uterine cervical cancer. This study included 1189 patients who underwent treatment for cervical cancer, including cervical intraepithelial neoplasm and adenocarcinoma in situ, at our hospital in Tokyo, Japan, in 2017-2018 and in 2021, before and after the pandemic, respectively. The patients' clinical information was compared during both periods. The clinical stage was unified using the International Federation of Gynecology and Obstetrics (FIGO) 2008 staging. The number of patients treated for cervical cancer was 355, 420, and 414 in 2017, 2018, and 2021, respectively. The percentage of invasive carcinomas significantly increased from 158 (44.5%) and 196 (46.7%) to 219 (52.9%) (p = 0.049). In all periods, no significant differences were observed in median age, histological type, and treatment. The proportions of FIGO Stage IA1 were significantly elevated from 3.9% and 3.8% to 11.4% (p < 0.001). The percentage of patients from prefectures other than Tokyo significantly increased from 34.9% to 40.8% (p = 0.049). Furthermore, the proportion of patients with invasive carcinoma in private clinics increased from 28.0% to 37.9% (p = 0.014). The number of patients with invasive carcinoma and the percentage of patients with invasive carcinoma referred from private clinics increased, indicating that the COVID-19 pandemic influenced patients to delay consultations. Furthermore, the surge in patients from other prefectures indicates that medical resources were more limited in rural areas, another impact of COVID-19.

Sensitivity, Specificity, and Cost-Benefit Effect Between Primary Human Papillomavirus Testing, Primary Liquid-Based Cytology, and Co-Testing Algorithms for Cervical Lesions.

Cytology has long been a major screening method for cervical cancer prevention. Human papillomavirus (HPV) testing has recently been introduced for cervical cancer screening, and HPV tests become a major screening method in some countries. To seek the optimal strategy considering the cost-effectiveness for cervical cancer screening, we compared the performance of primary LBC, primary HPV test, and LBC plus HPV co-test in real practice. From March 2016 to June 2018, 3742 patients were included in this study. Liquid-based cytology (LBC), HPV test, and histopathological assessment were performed in 3727, 1063, and 508 cases, respectively. The sensitivity, specificity, and cost-benefit effects of primary HPV, primary LBC, and co-test algorithms were simulated for 317 cases with LBC, HPV, and histopathological results. On the LBC, 13.0% of the cases were diagnosed with atypical squamous cells of undetermined significance or higher grade lesions. In the HPV test, high-risk HPV was found in 43.5%, and 11.9% was positive for HPV type 16 or 18. Among the three simulated algorithms, the co-test demonstrated the best sensitivity (97.5%) and the lowest specificity (50.3%). The primary LBC demonstrated the best specificity (53.5%) and a slightly better sensitivity, compare with the primary HPV (95.1% vs. 93.8%). Using the primary LBC algorithm, 82.0% can be determined without additional HPV test, whereas 50.1% could be determined without additional LBC using the primary HPV algorithm. The primary LBC algorithm for uterine cervical cancer (UCC) screening is comparable to the primary HPV algorithm and has the best cost-benefit effect among the three algorithms.

Clinical application of photoacoustic imaging for cervical precursor lesion detection.

Early diagnosis of a precursor lesion in the uterine cervix is an essential factor in uterine cervical cancer prevention. Although colposcopy is an established procedure for detecting high-risk patients, its accuracy and reproducibility are relatively low. Some supportive or alternative techniques to improve the early diagnosis of a precursor lesion have been studied, and correct diagnosis with high reliability using a minimally invasive, cost-effective technique has been pursued. This study aimed to examine the possibility of using photoacoustic (PA) imaging as a supportive technique to improve the accuracy of early diagnosis of cervical precursor lesions. A PA imaging system for microvessels was used to detect angiogenesis in severe lesions. A total of 21 patients who underwent surgical treatment and 114 outpatients who visited our colposcopy clinic were examined. A retrospective evaluation of PA images was performed as follows: (i) pathological assessment of the specific PA findings and (ii) retrospective evaluation of the severe lesion detection rate through PA. PA image evaluation and pathological findings showed dense angiogenesis in a severe precursor lesion appearing as a "hot spot" in the PA image. A comparison with colposcopy findings was performed for accuracy evaluation, and the detection rate of severe lesions using PA was relatively high (positive predictive value, 84.5%; negative predictive value, 82.1%). Our results indicate the possibility of using PA imaging for early diagnosis of severe cervical precursor lesions. With its ability to yield quantitative information, PA imaging can improve ultrasound diagnosis.

B-338 Real-world data shows the effectiveness of a tetravalent vaccine against Human Papilloma Virus types 16 and 18 in Chilean women

Abstract Background Cervical uterine cancer (CUCa) is the fourth most common female neoplasm globally. At least 99% of CUCa cases are caused by persistent infection of high-risk Human Papillomavirus (HR-HPV) types. In 2014, Chile began a mandatory immunization plan for 9-year-old girls with the GARDASIL™ vaccine, which confers immunity against types 16 and 18 that cause about 70% of CUCa. This work aims to estimate this vaccine's effectiveness in women after nine years of inoculation. Methods We evaluated the results for HPV detection from 21.676 women between 15 and 77 years old between 2019 and 2023 at Bupa Lab. HPV detection and genotyping was performed with the ROCHE Cobas® HPV Test. Effectiveness was measured as the ratio between the number of cases of HPV types 16+18 versus other HR-HPV. Results During the analyzed period, the number of tests performed increased significantly, and the positivity rate decreased from 44% in 2019 to 26,9% in 2023. Global positivity was 32% for some HR-HPV types, reaching a peak of 49,5% in the 20 to 24,9 years group. The average 16+18/other HR ratio was 0,39, which decreased significantly to 0,24 in the vaccinated group of women between 15 and 19,9 years, suggesting an effectiveness of 37,5% against HPV types 16 and 18 concerning the total HR types (Table 1). Conclusions In recent years, HPV detection has proven useful in preventive monitoring and early detection of CUCa. This increased awareness has triggered a significant rise in HPV testing and could be driving test positivity downwards. Although a more appropriate study design is required to estimate the actual effectiveness of the vaccine in Chile, our analyses showed a significant decrease in HPV types 16 and 18 in women after nine years of vaccination, which represents a crucial advance toward the eradication of CUCa.

Cardiac metastasis in uterine cervical cancer : Asystematic review and case study.

Cardiac metastasis from cervical cancer is rare and only scarcely documented. We aim to present anew case and systematically summarize the available literature. PubMed, Scopus, Web of Science, Central, and ClinicalTrials.gov were systematically searched following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) criteria. Results were screened via title, abstract, and full text. Additionally, the reference lists of all papers chosen for the review were screened. Eighty-one papers were identified, describing 86cases in total. Cardiac metastasis occurred at all stages of cervical cancer and in all age groups. Median time from initial diagnosis to diagnosis of cardiac metastasis was 12months. Patients mainly complained of dyspnea and chest pain, 60.8% had pathologic ECG (electrocardiographic) findings. The cardiac mass was most frequently detected by transthoracic echography. The most common tumor histology was squamous cell carcinoma. Chemotherapy and surgical interventions were the main treatment modalities. Median survival after diagnosis of cardiac metastasis was 3months. This largest review on cardiac metastases from cervical cancer confirmed the heart as avery infrequent site of metastasis. There are < 100 cases described in the literature, with very poor prognosis and undefined clinical management.

Utilizing CT imaging for evaluating late gastrointestinal tract side effects of radiotherapy in uterine cervical cancer: a risk regression analysis

BackgroundRadiotherapy (RT) is effective for cervical cancer but causes late side effects (SE) to nearby organs. These late SE occur more than 3 months after RT and are rated by clinical findings to determine their severity. While imaging studies describe late gastrointestinal (GI) SE, none demonstrate the correlation between the findings and the toxicity grading. In this study, we demonstrated the late GI toxicity prevalence, CT findings, and their correlation.MethodsWe retrospectively studied uterine cervical cancer patients treated with RT between 2015 and 2018. Patient characteristics and treatment(s) were obtained from the hospital’s databases. Late RTOG/EORTC GI SE and CT images were obtained during the follow-up. Post-RT GI changes were reviewed from CT images using pre-defined criteria. Risk ratios (RR) were calculated for CT findings, and multivariable log binomial regression determined adjusted RRs.ResultsThis study included 153 patients, with a median age of 57 years (IQR 49–65). The prevalence of ≥ grade 2 RTOG/EORTC late GI SE was 33 (27.5%). CT findings showed 91 patients (59.48%) with enhanced bowel wall (BW) thickening, 3 (1.96%) with bowel obstruction, 7 (4.58%) with bowel perforation, 6 (3.92%) with fistula, 0 (0%) with bowel ischemia, and 0 (0%) with GI bleeding. Adjusted RRs showed that enhanced BW thickening (RR 9.77, 95% CI 2.64–36.07, p = 0.001), bowel obstruction (RR 5.05, 95% CI 2.30–11.09, p < 0.001), and bowel perforation (RR 3.82, 95% CI 1.96–7.44, p < 0.001) associated with higher late GI toxicity grades.ConclusionsOur study shows CT findings correlate with grade 2–4 late GI toxicity. Future research should validate and refine these findings with different imaging and toxicity grading systems to assess their potential predictive value.

Diffusion Weighted Imaging for the Assessment of Lymph Node Metastases in Women with Cervical Cancer: A Meta-analysis of the Apparent Diffusion Coefficient Values

PurposeTo assess the diagnostic performance of Diffusion Weighted Imaging (DWI) and provide optimal apparent diffusion coefficient (ADC) cut-off values for differentiating between benign and metastatic lymph nodes in women with uterine cervical cancer. MethodMEDLINE and EMBASE databases were searched. Methodological quality was assessed with QUADAS-2. Data-analysis was performed for three subgroups: 1. All studies; 2. Studies with maximum b-values of 800 s/mm², and 3. Studies containing b-values of 1000 s/mm². Receiver-operating characteristics (ROC) curves were constructed and the area under the curve (AUC) was calculated. The maximum Youden index was used to determine optimal ADC cut-off values, following calculations of sensitivity and specificity. ResultsSixteen articles (1156 patients) were included. Overall, their quality was limited. For all studies combined, the optimum ADC cut-off value was 0.985 x 10⁻³ mm²/s at maximum Youden Index of 0.77, resulting in sensitivity and specificity of 84%, and 94%, respectively. Studies with b-values up to 800 s/mm², gave an optimum ADC cut-off value of 0.985 x 10⁻³ mm²/s at maximum Youden Index of 0.62, with a sensitivity and specificity of 62%, and 100%. Studies containing b-values of 1000 s/mm² gave an optimum ADC cut-off value of 0.9435 x 10⁻³ mm²/s at maximum Youden Index of 0.93, with a sensitivity and specificity of 100%, and 93%, respectively. ConclusionsStudies using DWI including b-values of 1000 s/mm² have higher sensitivity and specificity than those with b-values up to 800 s/mm². At the cut-off value of 0.9435 x 10⁻³ mm²/s DWI can sufficiently discriminate between benign and metastatic lymph nodes.

Identification of E3 ubiquitin ligase-associated prognostic genes and construction of a prediction model for uterine cervical cancer based on bioinformatics analysis

E3 ligases are engaged in a variety of physiological processes within cells and use ubiquitin-labeled substrates to control their activity and stability. Although some research has indicated that E3 ligases or particular substrates have an impact on the treatment that cervical cancer patients get after their diagnosis, The exact purpose of these enzymes in the occurrence and evolution of cancer of the cervical region (CC) is not clear. In order to extract and analyze relevant mRNA gene expression data as well as clinical patient data, we used open databases. A reliable risk prediction model was developed by applying the least absolute shrinkage and selection operator (LASSO) technique in conjunction with Cox regression analysis. Column-line plots were combined to analyze the predictive model, and the GSE44001 dataset served as an external validation.Four gene models:proteasome (prosome, macropain) 26S subunit, non-ATPase, 14(PSMD14),proteasome (prosome, macropain) subunit, alpha type, 4(PSMA4,),zinc finger and BTB domain containing 16(ZBTB16),and ankyrin repeat domain 9(ANKRD9). Gene expression levels in both healthy and cancerous tissues have been confirmed by the HPA database. Next, the investigation focused on immunological state and tumor mutation load. The high-risk group and Cluster B had distinct levels of immune cell infiltration and a worse prognosis. Additionally, KEGG and GO analyses of differentially expressed genes (DEGs) between the high- and low-risk groups were performed, as well as tumor microenvironment (TME) investigations. Targeting E3 ligases may be an efficient strategy to treat cervical cancer (CC), according to a novel and comprehensive E3 ubiquitination ligase-associated gene model that has been presented.

Comparing qSMI and qCEUS for assessing vascularization in uterine cervical cancer: operable versus non-operable group.

The present study aimed to compare the effectiveness and reliability of quantified superb microvascular imaging (qSMI) and quantified contrast-enhanced ultrasonography (qCEUS) in assessing vascularization in both operable and non-operable uterine cervical cancer. A case-control study included 64 patients with pathology-proven and untreated cervical cancer, who underwent transvaginal ultrasonography combined with qSMI and qCEUS between January 2022 and June 2023. SMI results were quantified as the vascular index (VI), which were compared to 12 quantitative parameters of CEUS calculated with time-intensity curves (TIC). According to FIGO staging and different treatment regimens, 64 patients with cervical cancer were divided into operable group (IA ~ IIA, n = 19) and non-operable group (IIB ~ IV, n = 45). In comparison to the operable group, the non-operable group showed significantly higher values in VI, peak intensity (PI), area under the curve (AUC), wash-in area (iAUC), wash-out area (oAUC), wash-in rate (WiR), mean intensity (Mean Int), and standard deviation (STD) (all P < 0.05). VI demonstrated strong correlations with CEUS parameters, notably PI (r = 0.854, P < 0.001) and AUC (r = 0.635, P < 0.001). Furthermore, VI showed a better predictive performance for treatment-group assignment than qCEUS parameters, with an 80.7% accuracy, 64.4% sensitivity and 89.5% specificity. Both qSMI and qCEUS exhibit significant and comparable utility in detecting microvascular hyperplasia and predicting treatment-group assignments in cervical cancer. Furthermore, qSMI may offer added convenience in implementation.

Causal relationship between gut microbiota and gynecological tumor: a two-sample Mendelian randomization study.

Previous research has established associations between alterations in gut microbiota composition and various gynecologic tumors. However, establishing a causal relationship between gut microbiota and these tumors remains necessary. This study employs a two-sample Mendelian randomization (MR) approach to investigate causality, aiming to identify pathogenic bacterial communities potentially involved in gynecologic tumor development. Data from the MiBioGen consortium's Genome-Wide Association Study (GWAS) on gut microbiota were used as the exposure variable. Four common gynecologic neoplasms, including uterine fibroids (UF), endometrial cancer (EC), ovarian cancer (OC), and cervical cancer (CC), were selected as outcome variables. Single-nucleotide polymorphisms (SNPs) significantly associated with gut microbiota were chosen as instrumental variables (IVs). The inverse variance-weighted (IVW) method was used as the primary MR analysis to assess the causal relationship. External validation An was conducted using an independent. Sensitivity analyses were performed to ensure robustness. Reverse MR analysis was also conducted to assess potential reverse causation. Combining discovery and validation cohorts, we found that higher relative abundance of Lachnospiraceae is associated with lower UF risk (OR: 0.882, 95% CI: 0.793-0.982, P = 0.022). Conversely, higher OC incidence is associated with increased relative abundance of Lachnospiraceae (OR: 1.329, 95% CI: 1.019-1.732, P = 0.036). Sensitivity analyses confirmed these findings' reliability. Reverse MR analysis showed no evidence of reverse causation between UF, OC, and Lachnospiraceae. This study establishes a causal relationship between Lachnospiraceae relative abundance and both UF and OC. These findings provide new insights into the potential role of gut microbiota in mechanisms underlying gynecological tumors development.

Impact of MRI radiomic feature normalization for prognostic modelling in uterine endometrial and cervical cancers

Widespread clinical use of MRI radiomic tumor profiling for prognostication and treatment planning in cancers faces major obstacles due to limitations in standardization of radiomic features. The purpose of the current work was to assess the impact of different MRI scanning- and normalization protocols for the statistical analyses of tumor radiomic data in two patient cohorts with uterine endometrial-(EC) (n = 136) and cervical (CC) (n = 132) cancer. 1.5 T and 3 T, T1-weighted MRI 2 min post-contrast injection, T2-weighted turbo spin echo imaging, and diffusion-weighted imaging were acquired. Radiomic features were extracted from within manually segmented tumors in 3D and normalized either using z-score normalization or a linear regression model (LRM) accounting for linear dependencies with MRI acquisition parameters. Patients were clustered into two groups based on radiomic profile. Impact of MRI scanning parameters on cluster composition and prognostication were analyzed using Kruskal–Wallis tests, Kaplan–Meier plots, log-rank test, random survival forests and LASSO Cox regression with time-dependent area under curve (tdAUC) (α = 0.05). A large proportion of the radiomic features was statistically associated with MRI scanning protocol in both cohorts (EC: 162/385 [42%]; CC: 180/292 [62%]). A substantial number of EC (49/136 [36%]) and CC (50/132 [38%]) patients changed cluster when clustering was performed after z-score-versus LRM normalization. Prognostic modeling based on cluster groups yielded similar outputs for the two normalization methods in the EC/CC cohorts (log-rank test; z-score: p = 0.02/0.33; LRM: p = 0.01/0.45). Mean tdAUC for prognostic modeling of disease-specific survival (DSS) by the radiomic features in EC/CC was similar for the two normalization methods (random survival forests; z-score: mean tdAUC = 0.77/0.78; LRM: mean tdAUC = 0.80/0.75; LASSO Cox; z-score: mean tdAUC = 0.64/0.76; LRM: mean tdAUC = 0.76/0.75). Severe biases in tumor radiomics data due to MRI scanning parameters exist. Z-score normalization does not eliminate these biases, whereas LRM normalization effectively does. Still, radiomic cluster groups after z-score- and LRM normalization were similarly associated with DSS in EC and CC patients.

Diagnostic Imaging Performance of Dual-Energy Computed Tomography Compared with Conventional Computed Tomography and Magnetic Resonance Imaging for Uterine Cervical Cancer.

Objective This article evaluates the ability of low-energy (40 keV) virtual monoenergetic images (VMIs) in the local diagnosis of cervical cancer compared with that of conventional computed tomography (C-CT) and magnetic resonance imaging (MRI), using clinicopathologic staging as a reference. Methods This prospective study included 33 patients with pathologically confirmed cervical cancer who underwent dual-energy CT and MRI between 2021 and 2022. The contrast-to-noise ratio (CNR) of the tumor-to-myometrium was compared between C-CT and VMI. Additionally, sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) for each local diagnostic parameter were compared between C-CT, VMI, and MRI. Interradiologist agreement was also assessed. Results The mean CNR was significantly higher on VMI ( p = 0.002). No significant difference in AUC was found between C-CT and VMI for all local diagnostic parameters, and the specificity of VMI was often significantly less than that of MRI. For parametrial invasion, mean sensitivity, specificity, and AUC for C-CT, VMI, and MRI were 0.81, 0.99, 0.93; 0.64, 0.35, 0.79; and 0.73, 0.67, 0.86, respectively, and MRI had significantly higher specificity and AUC than that of VMI ( p = 0.013 and 0.008, respectively). Interradiologist agreement was higher for VMI than C-CT and for MRI than VMI. Conclusion The CNR of VMI was significantly higher than C-CT and interradiologist agreement was better than with C-CT; however, the overall diagnostic performance of VMI did not significantly differ from C-CT and was inferior to MRI. VMI was characterized by low specificity, which should be understood and used for reading.

A transversal cross-sectional study of factors related to HPV vaccination status and cancer screening participation among French women aged 25–40

BackgroundIn 2020, uterine cervical cancer (UCC) was the 12th most common cancer among women in France and the 4th worldwide. French health authorities wanted to increase Human Papilloma Virus (HPV) vaccination and screening rates. There were still many barriers to these measures among young women, their families, and health professionals and teachers. Between 2014 and 2019, international studies found inconsistent effects of HPV vaccination on UCC screening. In 2022, a survey was conducted among women aged 25 to 40 in the Nord-Pas-de-Calais region to assess participation 1) in HPV vaccination and its barriers, 2) in UCC screening as a function of HPV vaccination status.MethodsData were collected using an anonymous online questionnaire distributed by QR code in 80 general practices randomly selected in the Nord-Pas-de-Calais region between January and June 2022. Results were analyzed bivariately using the Chi2 test, multivariately when numbers allowed, and in age subgroups (sensitivity analysis).Results407 complete questionnaires (for 602 participating women) were analyzed. In our sample, 41% of women aged 25 to 40 in the Nord-Pas-de-Calais region were vaccinated against HPV viruses in 2022. The risk factors for non-vaccination, after multivariable adjustment, were: the periods of eligibility for vaccination in the early days of French vaccination (2007–2012: odds ratio OR = 0.04 [95% CI, 0.02–0.09]; 2012–2017: OR = 0.5 [0.3–0.8]), information received from non-medical sources (OR = 0.3 [0.2–0.6]), and absence of information about vaccination (OR = 0.12 [0.05–0.27]). In our sample, 90% of women were screened for UCC. In bivariate analysis, women at risk of not being screened were those who were youngest, had been vaccinated against HPV, were not heterosexual, lived alone, had gynecological follow-up by their general practitioner, and did not have regular gynecological follow-up. Sensitivity analysis showed that the only risk factor significantly correlated with non-screening regardless of age group was lack of regular gynecological follow-up.ConclusionsParticipation in HPV vaccination and UCC screening is improved by medical education and gynecological follow-up. This multicenter study, limited by the relative youth of vaccination in France, should be repeated after 2037 to assess the possible effect of vaccination on screening.

Cost analysis of anticancer chemotherapy and chemoirradiation regimens considering the drugs marketed through Jan Aushadhi (People's Medicine) stores and their branded counterparts: First cost comparison study.

Chemotherapy in an integral part of cancer treatment, either administered alone or in combination with radiation. However, the cost of these drugs is often prohibitively high for most patients. To address this issue, the Government of India has established Jan Aushadhi (JAS) stores across the country, where affordable generic medicines are available. In the current study, we performed a cost minimization analysis comparing JAS drugs with branded chemotherapeutic drugs used in various cancer treatment regimens. This study was to conduct a cost-minimization analysis by comparing the costs of different regimens when using JAS drugs, the most expensive branded drugs, and the least expensive branded drugs in the treatment of cancer in India. The study focused on conducting a cost minimization analysis of various chemotherapy drugs used in the treatment of different cancers, considering the availability of anticancer drugs at JAS stores. The costs for different chemotherapy regimens, including both anticancer and supportive drugs, were calculated for single and complete cycles. The costs of the most expensive and least expensive branded drugs were noted from the Current Index of Medical Stores. The cost difference (CD) was calculated by subtracting the cost of the cheaper drug from that of the costliest brand. The cost ratio (CR) and the percentage of cost variation (PCV) were calculated for India-specific conditions. The study analyzed the CD for various regimens using JAS drugs for chemotherapy treatment of breast, esophagus, rectal, colon, stomach, prostate, ovary, endometrial, cervical, head and neck, lung, multiple myeloma, testicular, and lymphoma cancers. It also considered chemoirradiation regimens for brain, head and neck, anorectal, esophageal, and uterine cervical cancers. Significant CDs were observed when both anticancer and supportive drugs were obtained from JAS stores. To the best of the authors' knowledge, this is the first study to consider the CD, CR, and PCV for various regimens using JAS drugs, as well as the costliest and cheapest branded drugs in standard cancer treatment regimens. The results of this study are expected to assist healthcare professionals and pharmacists in understanding the cost-saving benefits of substituting expensive branded drugs with more affordable chemotherapeutic drugs for the treatment of cancer. This substitution can provide financial benefit for socioeconomically marginalized population.

Role of the gel spacer in safely delivering whole pelvic radiation therapy without central shielding in computed tomography-based image-guided adaptive brachytherapy for uterine cervical cancer patients

BackgroundTo protect the rectum and bladder from high dose exposure, the Japanese guidelines for managing uterine cervical carcinoma recommend pelvic irradiation with central shielding (CS). Conversely, the European Society for Radiotherapy and Oncology (ESTRO) and the American Brachytherapy Society (ABS) guidelines recommend delivering ≥ 85 Gy to high-risk clinical target volume D90 (CTVHR D90%). In this study, we investigated whether a gel spacer can enable the safe delivery of the ESTRO/ABS-recommended doses to the target while observing dose constraints for the OARs without using CS in external beam radiation therapy (EBRT). Materials and MethodsTwenty patients who received definitive radiation therapy without CS and were treated by brachytherapy with a gel spacer between April 2017 and May 2022 were retrospectively reviewed. The cumulative doses of EBRT and brachytherapy expressed in the form of the equivalent dose in 2 Gy fractions (EQD2) were calculated. Treatment outcomes and incidence of adverse events were also examined. ResultsThe median cumulative CTVHR D90%, rectum D2cm3, and bladder D2cm3 were 86.6 Gy (range, 69.8–103.7), 62.9 Gy (range, 55.3–72.5), and 72.0 Gy (range, 62.9–84.1), respectively. The median follow-up was 35.9 months (range, 10.9–70.3). The 2-year local control rate was 95% (95% CI: [69–99%]). There were no CTCAE ≥Grade 3 late gastrointestinal or genitourinary adverse events. ConclusionsThe use of gel spacer can enable ESTRO/ABS-recommended dose constraints even without using CS in EBRT, with favorable outcomes and low adverse event rates.

Findings and Challenges in Replacing Traditional Uterine Cervical Cancer Diagnosis with Molecular Tools in Private Gynecological Practice in Mexico.

We have been encouraging practicing gynecologists to adopt molecular diagnostics tests, PCR, and cancer biomarkers, as alternatives enabled by these platforms, to traditional Papanicolaou and colposcopy tests, respectively. An aliquot of liquid-based cytology was used for the molecular test [high-risk HPV types, (HR HPV)], another for the PAP test, and one more for p16/Ki67 dual-stain cytology. A total of 4499 laboratory samples were evaluated, and we found that 25.1% of low-grade samples and 47.9% of high-grade samples after PAP testing had a negative HR HPV-PCR result. In those cases, reported as Pap-negative, 22.1% had a positive HR HPV-PCR result. Dual staining with p16/Ki67 biomarkers in samples was positive for HR HPV, and 31.7% were also positive for these markers. Out of the PCR results that were positive for any of these HR HPV subtypes, n 68.3%, we did not find evidence for the presence of cancerous cells, highlighting the importance of performing dual staining with p16/Ki67 after PCR to avoid unnecessary colposcopies. The encountered challenges are a deep-rooted social reluctance in Mexico to abandon traditional Pap smears and the opinion of many specialists. Therefore, we still believe that colposcopy continues to be a preferred procedure over the dual-staining protocol.

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 2.0cm3 (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.

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

BackgroundMesonephric 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 presentationWe 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.ConclusionsThis 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.

Integration between the Papanicolaou smear test and detection of human papillomavirus DNA suggests the need to update the screening strategy for the prevention of cervical uterine cancer

Integration between the Papanicolaou smear test and detection of human papillomavirus DNA suggests the need to update the screening strategy for the prevention of cervical uterine cancer