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).
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.

BACKGROUND: Chemotherapy-associated ovarian damage (CAOD) is one of the most feared short- and long-term side effects of anticancer treatment in premenopausal women. Accumulating detailed data show that different chemotherapy regimens can lead to disturbance of ovarian hormone levels, reduced or lost fertility, and an increased risk of early menopause. Previous studies have often focused on the direct effects of chemotherapeutic drugs on ovarian follicles, such as direct DNA damage-mediated apoptotic death and primordial follicle burnout. Emerging evidence has revealed an imbalance in the ovarian microenvironment during chemotherapy. The ovarian microenvironment provides nutritional support and transportation of signals that stimulate the growth and development of follicles, ovulation, and corpus luteum formation. The close interaction between the ovarian microenvironment and follicles can determine ovarian function. Therefore, designing novel and precise strategies to manipulate the ovarian microenvironment may be a new strategy to protect ovarian function during chemotherapy.
OBJECTIVE: This review details the changes that occur in the ovarian microenvironment during chemotherapy and emphasizes the importance of developing new therapeutics that protect ovarian function by targeting the ovarian microenvironment during chemotherapy.
METHODS: A comprehensive review of the literature was performed by searching PubMed up to April 2024. Search terms included \'ovarian microenvironment\' (ovarian extracellular matrix, ovarian stromal cells, ovarian interstitial, ovarian blood vessels, ovarian lymphatic vessels, ovarian macrophages, ovarian lymphocytes, ovarian immune cytokines, ovarian oxidative stress, ovarian reactive oxygen species, ovarian senescence cells, ovarian senescence-associated secretory phenotypes, ovarian oogonial stem cells, ovarian stem cells), terms related to ovarian function (reproductive health, fertility, infertility, fecundity, ovarian reserve, ovarian function, menopause, decreased ovarian reserve, premature ovarian insufficiency/failure), and terms related to chemotherapy (cyclophosphamide, lfosfamide, chlormethine, chlorambucil, busulfan, melphalan, procarbazine, cisplatin, doxorubicin, carboplatin, taxane, paclitaxel, docetaxel, 5-fluorouraci, vincristine, methotrexate, dactinomycin, bleomycin, mercaptopurine).
RESULTS: The ovarian microenvironment shows great changes during chemotherapy, inducing extracellular matrix deposition and stromal fibrosis, angiogenesis disorders, immune microenvironment disturbance, oxidative stress imbalances, ovarian stem cell exhaustion, and cell senescence, thereby lowering the quantity and quality of ovarian follicles. Several methods targeting the ovarian microenvironment have been adopted to prevent and treat CAOD, such as stem cell therapy and the use of free radical scavengers, senolytherapies, immunomodulators, and proangiogenic factors.
CONCLUSIONS: Ovarian function is determined by its \'seeds\' (follicles) and \'soil\' (ovarian microenvironment). The ovarian microenvironment has been reported to play a vital role in CAOD and targeting the ovarian microenvironment may present potential therapeutic approaches for CAOD. However, the relation between the ovarian microenvironment, its regulatory networks, and CAOD needs to be further studied. A better understanding of these issues could be helpful in explaining the pathogenesis of CAOD and creating innovative strategies for counteracting the effects exerted on ovarian function. Our aim is that this narrative review of CAOD will stimulate more research in this important field.
BACKGROUND: Not applicable.

Microplastics (MPs) can enter the reproductive system and can be potentially harmful to human reproductive health. In this study, 13 types of microplastics (MPs) were identified in patient blood, cancer samples, and paracarcinoma samples using Raman spectroscopy, with polyethylene, polypropylene and polyethylene-co-polypropylene being the most abundant polymer types. Futher, cotton was also found in our study. The diversity and abundance of MPs were higher in blood samples than in cancerous tissues, and there was a significant positive correlation between diversity (p < 0.05). Furthermore, the diversity and abundance of MPs in cancerous tissues were higher than in paracancerous tissues. The dimensional sizes of MPs in these samples were also very similar, with the majority of detected MPs being smaller in size. Correlation analysis showed that patient\'s age correlated with the abundance of MPs in blood samples, body mass index (BMI) correlated with the abundance of MPs in cancerous tissues. Notably, the frequency with which patients consume bottled water and beverages may also increase the abundance of MPs. This study identifies for the first time the presence of MPs and cotton in cancerous and paracancerous tissues of human cervical cancer patients. This provides new ideas and basic data to study the risk relationship between MP exposure and human health.

OBJECTIVE: In the last decades FDG-PET/CT is increasingly used in combination with the standard diagnostic modalities (MRI + US-FNA) to identify residual neck disease (RND) after (chemo)radiotherapy for head-and-neck squamous cell carcinoma (HNSCC). The purpose of the current study is to identify the impact of increasing use of FDG-PET/CT on the accuracy of patient selection for salvage neck dissection (SND).
METHODS: Between 2008 and 2022, 908 consecutive patients with node-positive HNSCC were treated with (chemo)radiotherapy in our institution.
METHODS: positive predictive value (PPV) of FDG-PET/CT for pathologic-confirmed RND (pRND) after SND, compared to the standard of care; MRI + US-FNA. Secondary endpoints: oncologic outcomes.
RESULTS: Of the entire group, 130 patients (14 %) received SND. Of them only 53 patients (41 %) had pRND at the SND-specimens. The PPV of FDG-PET/CT for the detection of pRND was considerably better, compared to MRI + US-FNA; 89 % and 65 %, respectively. If FDG-PET/CT showed metabolic CR, these patients did not undergo SND. The NPV was 97.5 %, as only 2.5 % of these patients developed delayed regional failure. FDG-PET/CT considerably improved the accuracy of patient selection for SND, as significantly more patients treated in the second period, compared to first period of the study (n = 454 each) still had vital tumor at SND-specimen (53 % and 31 %, p = 0.008). Regional recurrence free-survival, DFS, OS and HNSCC-death were significantly worse in patients with pRND (p < 0.05) CONCLUSIONS: Incorporating FDG-PET/CT into the diagnostic pathway for the response evaluation after (chemo)radiotherapy significantly improved the accuracy of patient selection for SND and spared considerable number of patients (>20 %) from unnecessary SND. For patients with metabolic CR, SND can safely be omitted while for patients with no metabolic CR, SND is strongly advocated.

OBJECTIVE: To report the results of a multicenter cohort of preoperative brachytherapy (PBT) for treatment of early-stage cervical cancer (ESCC).
METHODS: A retrospective analysis was conducted among five French comprehensive cancer centers on behalf of the SFRO Brachytherapy Group to examine the outcome of patients with ESCC who received PBT between 2001 and 2019 because of adverse prognostic factors (tumor size >2 cm, presence of lymphovascular invasion, adenocarcinoma).Brachytherapy was followed 4-8 weeks later by surgery. Local relapse free, distant metastasis-free survival, disease-free, and overall survival and adverse effects were examined. Uni- and multivariate analyses were conducted looking for oncological prognostic factors.
RESULTS: A total of 451 patients were identified, with a mean tumor size of 24.7 mm. Adenocarcinoma accounted for 43.5% of cases, and lympho-vascular space invasion (LVSI) was present in 15.7%. A complete histological response was observed in 69.6%. With a mean follow-up of 75.4 months, DFS, LRFS, and OS rates at five years were 88% [95% CI (84-91), 98% [95% CI (96-99), and 92% [95% CI (87-95)], respectively. At the last follow-up, 8.2% of patients had died, including 31 (6.8%) from cervical cancer. Severe side effects range from 1.1% to 2%. At multivariate analysis, adenocarcinoma histological type, tumor size ≥2 cm, and the presence of residual tumors were prognosticators for DFS and DMFS.
CONCLUSIONS: PBT shows excellent oncological outcomes in this cohort of patients with adverse histoprognostic factors. Favorable survival rates and low complications rates were observed, supporting this strategy in the management of ESCC.

OBJECTIVE: To report the outcome of SLN staging in the SENTIX international prospective trial of SLN biopsy in patients with cervical cancer with an intensive ultrastaging protocol and central quality control and to evaluate how the intensity of pathological assessment correlates with metastatic detection rate in SLNs.
METHODS: Eligible were patients with stages T1a1/LVSI+ to T1b2 (<4 cm, ≤2 cm for fertility sparing), common tumor types, no suspicious lymph nodes on imaging, and bilateral SLN detection. SLNs were examined intraoperatively and processed by an intensive protocol for ultrastaging (paraffin blocks sectioned completely in 150-μm intervals/levels). SLNs from each site were submitted for central quality control.
RESULTS: In the SENTIX SLN study, 647 out of 733 enrolled patients underwent SLN ultrastaging, identifying 12.5% (81/647) with node positive, N1 cases. Intraoperative detection revealed metastases in 56.8% (46/81) of these cases, categorized into macrometastases (83.7%), micrometastases (26.3%), and isolated tumor cells (9.1%). Ultrastaging identified additional metastatic involvement in 43.2% (35/81) of patients, with detailed sectioning revealing metastases (MAC/MIC) at first level in 20 cases (24.7%), at levels 2-4 in 9 cases (11.1%), and at level ≥5 in 6 cases (7.4%).
CONCLUSIONS: SLN ultrastaging detects additional 43% of N1 (MAC/MIC) in patients with negative LNs by imaging and intraoperative pathological assessment. The detection rate of positive SLN correlates with the intensity (number of levels) of ultrastaging. Examination of four levels from paraffin blocks, which detects >90% of patients with N1, is a reasonable compromise for an international standard for ultrastaging.
BACKGROUND: NCT02494063 (ClinicalTrials.gov).

OBJECTIVE: This study aimed to systematically examine the relationship between polycystic ovary syndrome and ovarian, endometrial, and cervical cancers using the National Inpatient Sample (NIS) database.
METHODS: We utilized the International Classification of Diseases (ICD-10) system to identify relevant codes from the NIS database (2016-2019). Univariate and multivariable regression analyses (adjusted age, race, hospital region, hospital teaching status, income Zip score, smoking, alcohol use, and hormonal replacement therapy) were conducted to evaluate association between PCOS and gynecologic cancers. Results were summarized as odds ratio (OR) with 95% confidence intervals (CI).
RESULTS: Overall, 15,024,965 patients were analyzed, of whom 56,183 and 14,968,782 patients were diagnosed with and without PCOS, respectively. Among the patients diagnosed with gynecologic cancers (n = 91,599), there were 286 with PCOS and 91,313 without PCOS. Univariate analysis revealed that PCOS was significantly associated with higher risk of endometrial cancer (OR = 1.39, 95 % CI [1.18-1.63], p < 0.0001), but lower risk of ovarian cancer (OR = 0.55, 95 % CI [0.45-0.67], p < 0.0001) and cervical cancer (OR = 0.68, 95 % CI [0.51-0.91], p = 0.009). In contrast, after Bonferroni correction, multivariable analysis depicted that PCOS remained significantly associated with higher risk of endometrial cancer (OR = 3.90, 95 % CI [4.32-4.59], p < 0.0001). There was no significant correlation between PCOS and risk of ovarian cancer (OR = 1.09, 95 % CI [0.89-1.34], p = 0.409) and cervical cancer (OR = 0.83, 95 % CI [0.62-1.11], p = 0.218).
CONCLUSIONS: This first-ever NIS analysis showed that patients with PCOS exhibited unique gynecologic cancer risk profiles, with higher risk for endometrial cancer, and no significant risk for ovarian or cervical cancers.

OBJECTIVE: This study aimed to demonstrate the superiority of cryocompression over cryotherapy alone in the prevention of chemotherapy-induced peripheral neuropathy (CIPN) grade 2 or above.
METHODS: This prospective randomized study was conducted between May 2020 and January 2023 in Innsbruck. Eligible patients had a diagnosis of gynecological cancer and received a minimum of 3 cycles of taxane-based CT (neoadjuvant, adjuvant or palliative therapy). Patients were randomized 1:1 to receive either cryotherapy or cryocompression on their upper extremities during chemotherapy (CT). We performed temperature measurements, two QoL questionnaires and neurological tests during CT and at follow-up 3 and 6-9 months after the completion of CT. CIPN was assessed using the CTCAE score.
RESULTS: Of 200 patients recruited, both groups showed a lower prevalence of CIPN in this study compared to recent literature. In the group receiving cryotherapy, the prevalence of grade 1 CIPN was 30.1 %, and that of grade 2 CIPN or above was 13.7 %; in the group treated with cryocompression, the prevalence of grade 1 CIPN was 32.8 %, and that of grade 2 or above CIPN was 17.2 %. We found a significant reduction in temperature in the cryotherapy and cryocompression groups. Regarding the two QOL questionnaires as well as the neurological tests no significant differences were found between the two groups.
CONCLUSIONS: Our study suggests that cryotherapy as well as cryocompression is a safe and effective way to cool patients\' extremities to lower the prevalence of CIPN. Cryocompression was not more effective than cryotherapy alone in the prevention of CIPN.

Angiogenesis is considered a hallmark pathophysiological process in tumor development. Aberrant vasculature resulting from tumor angiogenesis plays a critical role in the development of resistance to breast cancer treatments, via exacerbation of tumor hypoxia, decreased effective drug concentrations within tumors, and immune-related mechanisms. Antiangiogenic therapy can counteract these breast cancer resistance factors by promoting tumor vascular normalization. The combination of antiangiogenic therapy with chemotherapy, targeted therapy, or immunotherapy has emerged as a promising approach for overcoming drug resistance in breast cancer. This review examines the mechanisms associated with angiogenesis and the interactions among tumor angiogenesis, the hypoxic tumor microenvironment, drug distribution, and immune mechanisms in breast cancer. Furthermore, this review provides a comprehensive summary of specific antiangiogenic drugs, and relevant studies assessing the reversal of drug resistance in breast cancer. The potential mechanisms underlying these interventions are discussed, and prospects for the clinical application of antiangiogenic therapy to overcome breast cancer treatment resistance are highlighted.

The aim of the present study was to explore the effects of dexmedetomidine (DEX) combined with ketorolac on postoperative patient-controlled analgesia (PCA), the balance of Th1/Th2 and the level of vascular endothelial growth factor (VEGF) in patients with cervical cancer following laparoscopic radical surgery. A total of 70 women with cervical cancer undergoing laparoscopic radical hysterectomy were enrolled in the study to randomly receive postoperative dexmedetomidine combined with ketorolac analgesia (DK group) and postoperative sufentanil analgesia (SUF group). The primary outcomes were the serum levels of interleukin-4 (IL-4), interferon-γ (IFN-γ) and VEGF, and the IFN-γ/IL-4 ratio 30 min before induction (T0), and 24 and 48 h after surgery. Secondary outcomes included numerical rating scale scores at 0 h (T0), 4 h (T1), 12 h (T2), 24 h (T3) and 48 h (T4) postoperatively, cumulative times of rescue analgesia, as well as the incidence of postoperative side effects within 48 h from surgery. Patients in the DK group reported similar analgesic effects as patients in the SUF group at T2, T3 and T4, and the incidence of postoperative nausea and vomiting was significantly lower in the DK group. In the DK group, the serum concentration of IFN-γ and IFN-γ/IL-4 ratio at 24 and 48 h after surgery were higher compared with those in the SUF group. Conversely, the serum concentrations of IL-4 at 24 h after surgery and VEGF at 24 and 48 h after surgery were significantly lower. The results indicated that the combination of DEX and ketorolac for PCA significantly improved postoperative pain and decreased the serum level of VEGF, which are associated with tumor angiogenesis. In addition, it maintained the homeostasis of postoperative immune dysfunction of patients with cervical cancer by shifting the balance between type 1 T helper cells and type 2 T helper cell (Th1/Th2 balance) to Th1 (registration no. ChiCTR1900027979; December 7, 2019).