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

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

Feasibility and Diagnostic Accuracy of Ultrastaging in the Detection of Micrometastases in Sentinel and Non-sentinel Lymph Nodes in Cervical Cancer: A Single-Center Retrospective Study With a Five-Year Follow-Up Period.

BACKGROUND: Cervical cancer is the fourth most common cause of malignant tumor-related deaths among women in developing nations. Cervical cancer has been estimated to cause 527.600 new cases and 265.700 deaths globally per year. OBJECTIVES: This study aimed to evaluate patients with cervical cancer by ultrastaging all the lymph nodes (LN), sentinel LN (SLN) and non-SLN, to increase the sensitivity of the detection of LN metastases and the diagnostic accuracy in cervical cancer with a five-year follow-up. MATERIALS AND METHODS: This is a retrospective study of 14 cervical cancer cases from 2017 to 2019 at the Municipal Emergency Clinical Hospital of Timisoara, Romania. The cases were selected based on their high risk of LN involvement but negative intraoperative pathologic LN. After re-evaluating all paraffin block biopsy samples from 29 cases, 14 cases were included in the study, which met all criteria for ultrastaging on surgical biopsy samples. RESULTS: Patients' ages included in the study ranged from 43 to 70 years (median: 57.14 years). According to the International Federation of Gynecology and Obstetrics (FIGO) staging, the majority of the patients were in stage IB: seven cases (50%). The study revealed a positive correlation between patient age and FIGO staging, with Pearson's correlation coefficient of 0.707 and a p-value of less than 0.05, indicating that older patients were more likely to be diagnosed with a higher FIGO stage. The mean follow-up was 34.5 months, and the median follow-up was 36 months (range: 6-60 months). We obtained 167 nodes, with a mean of 11.92 nodes/case. Twenty-one LN were found to be positive with the ultrastaging method. We detected 11 LN with macrometastases (MAC) (52.38%), seven with micrometastasis (MIC) (33.3%), and three with tumor cell islets (14.4%). That would be 13% of newly diagnosed ultrastaging cases as positive nodes. This ultrastaging method detected nodal MIC in eight (57.1%) out of the 14 patients, who initially tested negative for LN involvement using the routine Hematoxylin and Eosin (HE) method. The detection of micrometastases in these patients underscored the superior sensitivity of ultrastaging, which was further highlighted by the subsequent relapse of four (28.57%) out of these eight patients. The study also found no correlation between the FIGO standardization and the number of MIC found in these patients. CONCLUSIONS: Predicting cervical LN metastasis (LNM) is crucial for improving survival rates and reducing recurrence. Very few small cohort studies used an ultrastaging method to assess non-SLNs; most of them only assessed SLNs. We showed in our study that the ultrastaging method, both in the case of SLN and non-SLN, is superior compared with H&E analysis, with a 13% rate of new positive nodule diagnosis. Metastatic involvement of non-SLN was found in over 50% of all cases (8/14) according to the ultrastaging method. Additionally, our study confirms that the sensitivity of SLN ultrastaging is high for the presence of both MIC and MAC in SLN pelvic LN. As a result, we feel that ultrastaging is the most effective method for SLN analysis in patients with early-stage cervical cancer, and bilateral detection is preferable, significantly reducing false-negative results. The routine use of SLN along with ultrastaging would lead to more accurate surgical staging and better oncological follow-up of cases.

Cervical Cancer in Mexico: From a Renowned Vaccination Program to Unfulfilled Needs in Treatment Access.

Mexico's national human papillomavirus (HPV) vaccination program was established in 2008, providing free access to HPV vaccines and quickly becoming an immense success story, achieving significant coverage among young Mexican females. However, despite these efforts and notable achievements, cervical cancer caused mainly by HPV remains a challenging issue among Mexican women aged 15 years or older. A critical obstacle faced by women in the country is a lack of early detection and screening resources, coupled with delays in diagnosis and treatment, exacerbated by the poor distribution of already insufficient healthcare resources. This situation creates adverse conditions for the female demographic in the country. Our editorial aims to draw attention to the urgent need to improve access to adequate prevention, screening, and treatment for cervical cancer patients in Mexico, advocating for a collective effort between the Mexican government, public health professionals, and civil society.

The implications of hormone treatment for cancer risk, screening and treatment in transgender individuals.

There is evidence that gender-affirming hormone treatment (GAHT) for transgender individuals modulates their risk for specific malignancies including breast and prostate cancer, and meningiomas. However, there is insufficient data to make precise risk estimates accounting for age and inherited cancer risk. As such, screening recommendations remain broad. Even less evidence exists for best practice in the management of active or historical cancers in the transgender population. Guidance is therefore mainly extrapolated from cisgender populations but with considerations of the significant benefits of GAHT in the face of any hormonal risk. Clinical experience, the multidisciplinary team and shared decision making with the patient are vital in providing person-centred care, while further research is acquired.

An Intramyocardial Mass Mimicking ST-Segment Elevation Myocardial Infarct at Presentation.

ST-segment elevation on the electrocardiogram typically indicates acute myocardial infarction but can mimic ST-segment elevation myocardial infarction in various conditions. We present a case of a patient with an intramyocardial mass and anterior ST-segment elevation without significant myocardial biomarker elevation. Multimodality imaging was crucial in revealing cardiac metastasis as the attributable cause.

Rationale and design of the Self-TI Study protocol: a cross-sectional human papillomavirus self-testing pilot study among transgender adults in England.

INTRODUCTION: Persistent infection with high-risk human papillomavirus (HPV) is the causal agent of several cancers including cervical, anal and oropharyngeal cancer. Transgender men and transmasculine non-binary (TMNB) people with a cervix are much less likely to undergo cervical cancer screening than cisgender women. Transgender women and transfeminine non-binary (TWNB) people assigned male at birth may be at increased risk of HPV. Both TMNB and TWNB people face many barriers to HPV testing including medical mistrust due to stigma and discrimination. METHODS AND ANALYSIS: The Self-TI Study (Self-TI) is a pilot study designed to measure acceptability and feasibility of HPV self-testing among transgender and non-binary people in England. TMNB people aged 25-65 years, with at least 1 year of testosterone, and TWNB people, aged 18 years and over, are eligible to participate. Participants self-collect up to four samples: an oral rinse, a first void urine sample, a vaginal swab (if applicable) and an anal swab. TMNB participants are asked to have an additional clinician-collected cervical swab taken following their routine Cervical Screening Programme sample. TWNB people are asked to take a self-collection kit to perform additional self-collection at home and mail the samples back to the clinic. Acceptability is assessed by a self-administered online survey and feasibility is measured as the proportion of samples returned in the clinic and from home. ETHICS AND DISSEMINATION: Self-TI received ethical approval from the Research Ethics Committee of Wales 4 and ethical review panel within the Division of Cancer Epidemiology and Genetics at the US National Cancer Institute. Self-TI was coproduced by members of the transgender and non-binary community, who served as authors, collaborators and members of the patient and public involvement (PPI) group. Results of this study will be shared with the community prior to being published in peer-reviewed journals and the PPI group will help to design the results dissemination strategy. The evidence generated from this pilot study could be used to inform a larger, international study of HPV self-testing in the transgender and non-binary community. TRIAL REGISTRATION NUMBER: NCT05883111.

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

BACKGROUND: In 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. METHODS: Data 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). RESULTS: 407 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. CONCLUSIONS: Participation 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.

Predicting recurrence in intermediate­ and high­risk stage IB­IIB cervical cancer treated with adjuvant cisplatin and paclitaxel chemotherapy post­radical hysterectomy: The role of TBX2 expression.

Cervical cancer remains a significant global health concern despite advances in prevention and treatment. Current management for intermediate- to high-risk stage IB-IIB cervical cancer post-radical hysterectomy involves irradiation or concurrent chemoradiation, although patients can exhibit several adverse events. Adjuvant chemotherapy has emerged as a promising alternative; however, its efficacy remains unclear. T-box (TBX)2 is a transcription factor that is involved in the regulation of cell cycle progression during cancer and embryonic development. Additionally, elevated expression of TBX2 is associated with resistance to DNA-damaging chemotherapeutic agents, such as cisplatin, carboplatin and doxorubicin. The aim of the present study was to investigate the relationship between TBX2 expression and recurrence in patients receiving adjuvant cisplatin and paclitaxel (TP) chemotherapy post-radical hysterectomy. Additionally, the impact of TBX2 knockdown on cisplatin sensitivity was assessed in vitro. A retrospective analysis was performed on 100 patients. Patients were categorized into two groups based on recurrence within 2 years of treatment initiation: The non-recurrent group (n=85) and the recurrent group (n=15). TBX2 expression was assessed immunohistochemically, and multiple logistic regression analysis was performed to identify predictors of recurrence. Additionally, the impact of small interfering RNA-mediated TBX2 knockdown on cervical cancer cell sensitivity to cisplatin was evaluated. TBX2 expression was significantly higher in the recurrent group compared with that in the non-recurrent group (P<0.01). Patients were stratified into low TBX2 expression (weighted score ≤8; n=80) and high TBX2 expression (weighted score ≥9; n=20) groups. The high TBX2 expression group exhibited a higher recurrence rate compared with the low expression group (P<0.01). Multivariate analysis identified TBX2 expression as an independent predictor of recurrence (P<0.01). Moreover, TBX2 knockdown significantly enhanced cervical cancer cell sensitivity to cisplatin in vitro (P<0.05). These findings highlight TBX2 expression as a potential predictive biomarker for recurrence amongst patients with intermediate- to high-risk stage IB-IIB cervical cancer receiving adjuvant TP chemotherapy post-radical hysterectomy.

Combining multimodal diffusion-weighted imaging and morphological parameters for detecting lymph node metastasis in cervical cancer.

BACKGROUND: Accurate detection of lymph node metastasis (LNM) is crucial for determining the tumor stage, selecting optimal treatment, and estimating the prognosis for cervical cancer. This study aimed to assess the diagnostic efficacy of multimodal diffusion-weighted imaging (DWI) and morphological parameters alone or in combination, for detecting LNM in cervical cancer. METHODS: In this prospective study, we enrolled consecutive cervical cancer patients who received multimodal DWI (conventional DWI, intravoxel incoherent motion DWI, and diffusion kurtosis imaging) before treatment from June 2022 to June 2023. The largest lymph node (LN) observed on each side on imaging was matched with that detected on pathology to improve the accuracy of LN matching. Comparison of the diffusion and morphological parameters of LNs and the primary tumor between the positive and negative LN groups. A combined diagnostic model was constructed using multivariate logistic regression, and the diagnostic performance was evaluated using receiver operating characteristic curves. RESULTS: A total of 93 cervical cancer patients were enrolled: 35 with LNM (48 positive LNs were collected), and 58 without LNM (116 negative LNs were collected). The area under the curve (AUC) values for the apparent diffusion coefficient, diffusion coefficient, mean diffusivity, mean kurtosis, long-axis diameter, short-axis diameter of LNs, and the largest primary tumor diameter were 0.716, 0.720, 0.716, 0.723, 0.726, 0.798, and 0.744, respectively. Independent risk factors included the diffusion coefficient, mean kurtosis, short-axis diameter of LNs, and the largest primary tumor diameter. The AUC value of the combined model based on the independent risk factors was 0.920, superior to the AUC values of all the parameters mentioned above. CONCLUSION: Combining multimodal DWI and morphological parameters improved the diagnostic efficacy for detecting cervical cancer LNM than using either alone.

Successful management of locally advanced cervical cancer via total pelvic exenteration following neoadjuvant chemotherapy.

Stage IVA cervical cancer is a tumor that invades the mucosa of the bladder or rectum without distant metastasis and is difficult to treat, and concurrent chemoradiotherapy is recommended. Although radical surgery following neoadjuvant chemotherapy is a treatment option for stage IVA cervical cancer, the evidence is limited. A 51-year-old woman with bulky cervical cancer and rectal invasion was referred to our hospital. Paclitaxel and cisplatin were administered as neoadjuvant chemotherapies. After two cycles of chemotherapy, the tumor size decreased markedly. Total pelvic exenteration was performed, and a complete resection was achieved. Four cycles of paclitaxel and cisplatin were administered postoperatively. Thirty-three months after the completion of adjuvant chemotherapy, the patient was alive and free of disease. Radical surgery after neoadjuvant chemotherapy may be a treatment option for stage IVA cervical cancer with bulky tumors.

Multiparametric mri-based radiomics nomogram for predicting lymph-vascular space invasion in cervical cancer.

PURPOSE: To develop and validate a multiparametric magnetic resonance imaging (mpMRI)-based radiomics model for predicting lymph-vascular space invasion (LVSI) of cervical cancer (CC). METHODS: The data of 177 CC patients were retrospectively collected and randomly divided into the training cohort (n=123) and testing cohort (n = 54). All patients received preoperative MRI. Feature selection and radiomics model construction were performed using max-relevance and min-redundancy (mRMR) and the least absolute shrinkage and selection operator (LASSO) on the training cohort. The models were established based on the extracted features. The optimal model was selected and combined with clinical independent risk factors to establish the radiomics fusion model and the nomogram. The diagnostic performance of the model was assessed by the area under the curve. RESULTS: Feature selection extracted the thirteen most important features for model construction. These radiomics features and one clinical characteristic were selected showed favorable discrimination between LVSI and non-LVSI groups. The AUCs of the radiomics nomogram and the mpMRI radiomics model were 0.838 and 0.835 in the training cohort, and 0.837 and 0.817 in the testing cohort. CONCLUSION: The nomogram model based on mpMRI radiomics has high diagnostic performance for preoperative prediction of LVSI in patients with CC.

Primary human papillomavirus testing by clinician- versus self-collection: Awareness and acceptance among cervical cancer screening-eligible women.

OBJECTIVES: Primary human papillomavirus (HPV) testing by clinician-collection is endorsed by U.S. guideline organizations for cervical cancer screening, but uptake remains low and insights into patients' understanding are limited. This study aims to primarily address patient awareness of primary HPV screening by clinician-collection and acceptance of primary HPV screening by clinician- and self-collection, and secondarily assess factors associated with awareness and acceptance. SETTING: Primary care practices affiliated with an academic medical center. METHODS: A cross-sectional survey study of screening-eligible women aged 30-65 years was conducted to assess awareness and acceptability of primary HPV screening. We analyzed bivariate associations of respondent characteristics with awareness of primary HPV screening by clinician-collection, willingness to have clinician- or self-collected primary HPV testing, and reasons for self-collection preference. RESULTS: Respondents (n = 351; response rate = 23.4%) reported cervical cancer screening adherence of 82.8% but awareness of clinician-collected primary HPV as an option was low (18.9%) and only associated with HPV testing with recent screening (p = 0.003). After reviewing a description of primary HPV screening, willingness for clinician-collected (81.8%) or home self-collected (76.1%) HPV testing was high, if recommended by a provider. Acceptability of clinician-collected HPV testing was associated with higher income (p = 0.009) and for self-collection was associated with higher income (p = 0.002) and higher education (p = 0.02). Higher education was associated with reporting self-collection as easier than clinic-collection (p = 0.02). Women expected self-collection to be more convenient (94%), less embarrassing (85%), easier (85%), and less painful (81%) than clinician-collection. CONCLUSIONS: Educational interventions are needed to address low awareness about the current clinician-collected primary HPV screening option and to prepare for anticipated federal licensure of self-collection kits. Informing women about self-collection allows them to recognize benefits which could address screening barriers.

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.

Variables that impact HPV test accuracy during vaginal self collection workflow for cervical cancer screening.

Vaginal self collection (SC) is safe and effective for human papillomavirus (HPV) testing and can increase cervical cancer screening coverage for underserved women. To better understand the impact of SC methodology on HPV test outcomes, empirical testing was conducted using different swab collection workflows. Deposition of the collection swab into resuspension buffer resulted in a 2.4-cycle reduction in threshold detection of human beta-hemoglobin during PCR when compared to "swirl-and-toss". In addition, reducing the swab resuspension volume from 10 mL to 3 mL resulted in a 2.6-cycle reduction in threshold detection of human beta-globin. A systematic literature search (01/01/2020 to 08/02/2023) of Ovid Medline and Embase, followed by data extraction and analysis, was conducted to further assess the impact of resuspension volume on performance following SC. HPV test performance for SC, relative to clinician collection (CC), was calculated for detection of cervical pre-cancer. Data were stratified by the resuspension volume ratio of SC to CC being either ≥ 1.0 or < 1.0. SC with a volume ratio of ≥ 1.0 and < 1.0 had a relative ≥ CIN2 sensitivity of 92.0 % (95 % CI: 88.0, 96.0) and 97.0 % (95 % CI: 94.0, 100), respectively. Taken together, these results suggest that SC conditions can be modified to optimize sample recovery and performance, as part of cervical cancer screening.

Risk factors for the development of cervical cancer: analysis of the evidence.

Introduction: Cervical cancer (CC) is the fourth most prevalent female cancer globally. Understanding its epidemiology is crucial for devising practical strategies suited to geographic and social contexts to attain the global eradication of CC. Hence, this study examined the latest evidence of risk factors contributing to CC development. Methods: An independent literature search was conducted on PubMed using MESH terms. The primary sources were meta-analyses published from 2010 to 2023, which detail updated evidence on risk factors associated with CC. Additionally, the quality of the evidence was evaluated using the GRADE system and recommendations were made accordingly. Results: The main risk factors related to the cause of CC include co-infections with other sexually transmitted infections, genetic markers, cervicovaginal microbiota, nutritional factors, comorbidities that affect the immune response, smoking, and the use of hormonal contraceptives with a quality evidence based on the GRADE scale moderate. Conclusions: Since the necessary cause for CC is persistent cervicovaginal HPV, all the risk factors implicated in the causality of CC act as non-independent cofactors that increase the risk of CC. Thus, changes in public policies aimed at addressing these risk factors are highly recommended and can substantially decrease the risk of CC.

Female sexual function in long-term cervical cancer survivors compared with healthy women and women affected by benign gynecological disorders.

OBJECTIVE: To compare the female sexual function between cervical cancer survivors and healthy women or with benign gynecological diseases. STUDY DESIGN: From January 1, 2010 to January 31, 2019, a case-control study was conducted to compare the female sexual function of 106 cervical cancer survivors from a tertiary hospital and 185 women admitted to a gynecological outpatient clinic from the same health area for a routine gynecological examination (n=46) or for a benign gynecological disorder (symptomatic, n=113; asymptomatic, n=26). We prospectively assessed the female sexual function using the Female Sexual Function Index (FSFI). For the contrastive analysis hypothesis, we employed R statistical software. RESULTS: Cervical cancer survivors reported lower sexual activity rates than controls, in general, did (47.12% vs. 88.65%, p=0.0001), and, particularly, compared with healthy and symptomatic controls (47.12% vs. 82.61%, p=0.003; 47.12% vs. 87.61%, p=0.0001, respectively). Sixty and fifty-eight hundredths percent of the cervical cancer survivors experienced female sexual dysfunction, mainly due to hypoactive sexual desire (93.27%). Female sexual dysfunction was diagnosed in 64.32% of the controls, with sexual arousal disorders being the most common diagnosis (44.86%). Compared with controls, cervical cancer survivors exhibited considerably lower FSFI total scores and in sexual desire and lubrication domains (p <0.000; p <0.0001; p=0.023). CONCLUSIONS: Cervical cancer survivors had worse female sexual function and less sexual activity than controls did, although scores in both groups were in range of FSD. Rates of female sexual dysfunction were similar across cervical cancer survivors and controls, with hypoactive sexual desire and sexual arousal disorders as the most common diagnoses, respectively.

A rare case of Blastic plasmacytoid dendritic cell neoplasm with gynecologic presentation.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematological malignancy characterized by the proliferation of plasmacytoid dendritic cells with a blast-like appearance. It usually presents in elderly people, and clinical manifestations include nodular blue-violet skin lesions, bone marrow infiltration and, less frequently, extramedullary involvement. Gynecological manifestation (breast mass and exocervical lesion) is an unusual and rare presentation. Herein, we report the case of a 51-year-old woman patient who presented with a history of a rapidly growing and bleeding breast mass, along with a decline in general health. Notably, the disease had multifocal involvement, affecting the breast, uterine cervix, and cervical lymphadenopathy. Biopsies were performed on the breast mass and cervical lesion. Histopathological examination showed a diffuse lymphoid proliferation. The neoplastic cells show immunoreactivity for CD45 and CD56. The myelogram showed a 50 % excess of blasts with a heterogeneous appearance with the presence of cells that could suggest dendritic plasmacytoid cells. Bone marrow immunophenotyping showed the presence of blast-like cells that were positive for CD4, CD56, CD123, which supported the diagnosis of BPDCN. Despite initiating chemotherapy, the patient's condition rapidly deteriorated, highlighting the aggressive nature of BDCP. This case underscores the importance of early detection and the need for further research to improve outcomes for this rare condition.

Preliminary result of combined treatment with scanning carbon-ion radiotherapy and image-guided brachytherapy for locally advanced cervical adenocarcinoma.

Although there is growing evidence of the efficacy of carbon-ion radiotherapy (CIRT) for locally advanced cervical adenocarcinoma, reports on combined treatment with CIRT and image-guided brachytherapy (IGBT) are scarce. We retrospectively analyzed patients with International Federation of Gynecology and Obstetrics (2008) stage II-IVA locally advanced cervical adenocarcinoma who received combined scanning CIRT (sCIRT) and IGBT between April 2019 and March 2022. sCIRT consisted of whole-pelvic irradiation with 36 Gy (relative biological effectiveness [RBE]) in 12 fractions and subsequent local boost irradiation with 19.2 Gy (RBE) in 4 fractions. Three sessions of IGBT were administered after completion of sCIRT. Concurrent chemotherapy using weekly cisplatin (40 mg/m2/week) was also administered. Efficacy, toxicity and dose-volume parameters were analyzed. Fifteen patients were included in the analysis. The median follow-up period was 25 months. The 2-year overall survival, progression-free survival and local control rates were 92.3% (95% confidence interval [CI] = 77.8-100%), 52.5% (95% CI = 26.9-78.1%) and 84.8% (95% CI = 65.2-100%), respectively. Neither severe acute toxicity necessitating treatment cessation nor grade 3 or higher late toxicity were observed. The sigmoid D2cm3 of the patient who developed grade 2 late sigmoid hemorrhage was 65.6 Gy, which exceeded the standard deviation and target dose. The combination of sCIRT and IGBT for locally advanced cervical adenocarcinoma showed acceptable efficacy and safety. Further large-scale and long-term studies are warranted to confirm the efficacy and safety of this treatment.

Bone Marrow Sparing by Intensity Modulated Proton Beam Therapy in Postoperative Irradiation of Gynecologic Malignancies.

Purpose: The aim of this matched-pair cohort study was to evaluate the potential of intensity-modulated proton therapy (IMPT) for sparring of the pelvic bone marrow and thus reduction of hematotoxicity compared to intensity-modulated photon radiotherapy (IMRT) in the setting of postoperative irradiation of gynaecological malignancies. Secondary endpoint was the assessment of predictive parameters for the occurrence of sacral insufficiency fractures (SIF) when applying IMPT. Materials and Methods: Two cohorts were analyzed consisting of 25 patients each. Patients were treated with IMPT compared with IMRT and had uterine cervical (n = 8) or endometrial cancer (n = 17). Dose prescription, patient age, and diagnosis were matched. Dosimetric parameters delivered to the whole pelvic skeleton and subsites (ilium, lumbosacral, sacral, and lower pelvis) and hematological toxicity were evaluated. MRI follow-up for evaluation of SIF was only available for the IMPT group. Results: In the IMPT group, integral dose to the pelvic skeleton was significantly lower (23.4GyRBE vs 34.3Gy; p < 0.001), the average V5Gy, V10Gy, and V20Gy were reduced by 40%, 41%, and 28%, respectively, compared to the IMRT group (p < 0.001). In particular, for subsites ilium and lower pelvis, the low dose volume was significantly lower. Hematotoxicity was significantly more common in the IMRT group (80% vs 32%; p = 0009), especially hematotoxicity ≥ CTCAE II (36% vs 8%; p = 0.037). No patient in the IMPT group experienced hematotoxicity > CTCAE II. In the IMPT cohort, 32% of patients experienced SIF. Overall SIF occurred more frequently with a total dose of 50.4 GyRBE (37.5%) compared to 45 GyRBE (22%). No significant predictive dose parameters regarding SIF could be detected aside from a trend regarding V50Gy to the lumbosacral subsite. Conclusion: Low-dose exposure to the pelvic skeleton and thus hematotoxicity can be significantly reduced by using IMPT compared to a matched photon cohort. Sacral insufficiency fracture rates appear similar to reported rates for IMRT in the literature.

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.

BACKGROUND: To 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 METHODS: Twenty patients who received definitive radiation therapy without CS and were treated by brachytherapy with a gel spacer between 2017 and 2022 were retrospectively reviewed. The cumulative doses of EBRT and brachytherapy treatment outcomes and incidence of adverse events were also examined. RESULTS: The median cumulative CTVHR D90%, rectum D2cm3, and bladder D2cm3 were 86.6 Gy, 62.9 Gy, and 72.0 Gy, respectively. The 2-year local control rate was 95%. There were no CTCAE ≥Grade 3 late gastrointestinal or genitourinary adverse events. CONCLUSIONS: The 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.