Search Results (544)

Objective: This study aimed to investigate the impact of depression and anxiety disorders on mortality in women diagnosed with gynecologic cancers, utilizing nationwide retrospective cohort data. Methods: Data from the Korean National Health Insurance Service (NHIS) database, covering women diagnosed with cervical, endometrial, or ovarian cancers between 2007 and 2014, were analyzed. Women diagnosed with depression or anxiety disorders within one year after cancer diagnosis were identified and compared with a control group comprising patients with gynecologic cancers who did not develop either disorder during the same post-diagnosis period. Mortality was evaluated as the primary outcome. Results: Of 85,327 women analyzed, 784 (0.9%) were diagnosed with depression or anxiety disorders. Patients with depression or anxiety exhibited significantly higher mortality (38.4% vs. 29.9%; p < 0.001). Multivariate analysis indicated that depression significantly increased mortality risk (OR 1.46, 95% CI 1.27–1.66), whereas anxiety alone showed no significant effect (OR 0.97, 95% CI 0.74–1.27). Combined depression and anxiety showed the highest mortality risk (OR 1.47, 95% CI 1.31–1.65). Conclusions: Depression and anxiety disorders are significant predictors of increased mortality in women with gynecologic cancers, emphasizing the necessity for integrated mental health assessment and interventions in oncologic care to improve both survival and quality of life. Full article

High-grade serous ovarian cancer (HGSC) is a heterogeneous disease. RNA sequencing (RNAseq) of bulk solid tissue is of limited use in these populations due to heterogeneity. Single-cell RNA-seq (scRNA-seq) allows for the identification of diverse genetic compositions of heterogeneous cell populations. New computational methodologies are now available that use scRNAseq results to estimate cell type proportions in bulk RNAseq data. We performed bulk RNA-seq gene expression analysis on 112 HGSC specimens and 12 benign fallopian tube (FT) controls. We identified several publicly available scRNAseq datasets for use as annotation and reference datasets. Deconvolution was performed with MUlti-Subject SIngle Cell Deconvolution (MuSiC) to estimate cell type proportions in the bulk RNA-seq data. Datasets from the Cancer Genome Atlas (TCGA). HGSC repositories were also evaluated. Clinical variables and percentages of cell types were compared for differences in clinical outcomes and treatment results. Pathway enrichment analysis was also performed. Different annotations for referenced scRNA-seq datasets used for deconvolution of bulk RNA-seq data revealed different cellular proportions that were significantly associated with clinical outcomes; for example, higher proportions of macrophages were associated with a better response to primary chemotherapy. Our deconvolution study of bulk RNAseq HGSC samples identified cell populations within the tumor that may be associated with some of the observed clinical outcomes. Full article

High-grade serous ovarian cancer (HGSOC) is the most common and aggressive subtype of ovarian cancer, accounting for approximately 70% of cases. This study investigates genetic mutations and their associations with overall survival (OS), complete cytoreduction (R0), and platinum response in patients undergoing either primary debulking surgery followed by adjuvant chemotherapy (PDS) or neoadjuvant chemotherapy followed by interval debulking surgery (NACT). Genetic analysis was performed on 43 primary HGSOC tumor samples using targeted massive parallel sequencing via next-generation sequencing (NGS). Clinical and molecular data were evaluated collectively and through subgroup comparisons between PDS and NACT cohorts. All analyzed samples harbored genetic alterations. Univariate survival analysis revealed that the total number of mutations (p = 0.0035), as well as mutations in HRAS (p = 0.044), FLT3 (p = 0.023), TP53 (p = 0.03), and ERBB4 (p = 0.007), were significantly associated with poorer OS. Multivariate Cox regression integrating clinical and molecular data confirmed that ERBB4 mutations are independently associated with adverse outcomes. These findings reveal a distinctive mutational landscape between the PDS and NACT groups and suggest that ERBB4 alterations may define a particularly aggressive tumor phenotype. This study contributes to a deeper understanding of HGSOC biology and may support the development of novel therapeutic targets and personalized treatment strategies in the context of precision oncology. Full article

Purpose: To review parental pre-pregnancy and pregnancy exposures in relation to pediatric cancer (diagnosis before age 20). Methods: We conducted literature searches using Ovid Medline and Scopus to find primary research studies, review articles, and meta-analyses published from 2014 to 17 March 2021. Results: Strong evidence links increased risk of childhood cancer with maternal diabetes, age, and alcohol and coffee consumption during pregnancy. Both paternal and maternal cigarette smoking before and during pregnancy are associated with childhood cancers. Diethylstilbestrol (DES) exposure in utero has long been known to be causally associated with increased risk of vaginal/cervical cancers in adolescent girls. More recent evidence implicates in utero DES exposure to testicular cancer in young men and possible intergenerational effects on ovarian cancer in the granddaughters of women exposed to DES during pregnancy. There is strong evidence that childhood cancer risk is also associated with both high and very low birth weight and with gestational age. Evidence is also strong for the protective effects of maternal vitamin consumption and a healthy diet during pregnancy. Unlike early studies, those reviewed here show no association between in utero exposure to medical ionizing radiation, which may be explained by reductions over time in radiation doses, avoidance of radiation during pregnancy, and/or by inadequate statistical power to detect small increases in risk, rather than a lack of causal association. Evidence is mixed or conflicting for an association between childhood cancer and maternal obesity, birth order, cesarean/instrumental delivery, and prenatal exposure to diagnostic medical radiation. Evidence is weak or absent for associations between childhood cancer and multiple gestations or assisted reproductive therapies, as well as prenatal exposure to hormones other than DES, and medications. Full article

Adjuvant endocrine therapy for early breast cancer significantly reduces recurrence but increases bone fragility. Given limited data on denosumab (60 mg every 6 months) in premenopausal patients receiving endocrine therapy for early breast cancer, we conducted a retrospective real-world study at the Gemelli Hospital (September 2018–January 2025). A descriptive analysis was performed. The primary endpoint was to assess efficacy, evaluated by changes in bone mineral density via dual-energy X-ray absorptiometry and by monitoring bone turnover markers, particularly serum C-terminal telopeptide of type I collagen. Safety was evaluated based on adverse endocrine therapy events (osteoporotic fractures) and adverse denosumab events (osteonecrosis of the jaw). Sixty-nine patients were eligible for the study. Endocrine therapy included ovarian function suppression with exemestane (89.8%) or tamoxifen (10.1%). Baseline spinal osteoporosis decreased from 20.3% to 5.8%, osteopenia from 39.1% to 34.8%, with normal T-scores rising from 17.4% to 34.8%. Femoral improvements were similar. Serum C-terminal telopeptide of type I collagen levels (evaluated in 35.8%) showed stable reduction in 97%. Denosumab adherence was 89.9%. One osteonecrosis of the jaw case occurred (1.4%); no fractures were reported. Denosumab demonstrated efficacy in improving bone density and reducing bone turnover, with excellent adherence and favorable safety. Longer follow-up is needed to assess post-discontinuation effects. Full article

The concept of “more is better” has long dominated cancer treatment, emphasizing aggressive therapies despite their toxicity. However, the rise of personalized medicine has fostered treatment de-escalation strategies aimed at minimizing toxicity, improving quality of life, and reducing costs. This position paper highlights key applications of de-escalation in medical oncology, with a primary focus on breast cancer and notable examples in colorectal, head and neck, ovarian, lung, and prostate cancers. Various approaches, including dose reduction, treatment duration shortening, and regimen optimization, have demonstrated efficacy without compromising clinical outcomes. Advances in molecular diagnostics, such as Oncotype Dx in breast cancer and circulating tumor DNA (ctDNA) analysis in colorectal cancer, have facilitated patient selection for de-escalation. While these strategies present promising results, challenges remain, particularly in balancing treatment intensity with oncologic control. The review underscores the need for further prospective trials to refine de-escalation approaches and ensure their safe integration into standard oncologic care. Full article

Background: Assessment of the peritoneal cancer burden is crucial for determining the optimal treatment in advanced ovarian cancer (AOC). Effective non-invasive methods to predict tumour load remain limited. This study aimed to assess the applicability of 2-[¹⁸F]FDG PET/CT volumetric parameters, metabolic tumour volume (MTV), and total lesion glycolysis (TLG) for predicting the surgical peritoneal cancer index (PCI) in AOC before primary treatment. Methods: Patients with high-grade serous or undifferentiated AOC who underwent surgical PCI evaluation and 2-[¹⁸F]FDG PET/CT between 01/2013 and 12/2018 were included. MTV and TLG were calculated using thresholds of 40% and 50% (MTV40, MTV50, TLG40, and TLG50). Correlations between the peritoneal carcinomatosis MTV (car_MTV) and TLG (car_TLG) were analysed. The capacity of volumetric parameters to estimate PCIs above or below 14 and 20 was assessed for the whole abdominal cavity and in per-quadrant analysis, specifically for upper-abdomen areas 1, 2, and 3 (MTV40_1, 2, 3 and TLG40_1, 2, 3). Results: MTV40, MTV50, TLG40, and TLG50 significantly correlated with the PCI in the final study population (n = 45). MTV40 showed a Pearson coefficient of 0.41 (p = 0.003). MTV3_40 (AUC 0.79) and TLG3_40 (AUC 0.81) presented the highest AUCs for predicting a PCI above or below 14. The volumetric parameters allowed the prediction of a PCI greater or less than 20, with an AUC of 0.77 for MTV40_1 and 0.78 for TLG40_1. Conclusions: 2-[¹⁸F]FDG PET/CT MTV and TLG correlate significantly with the surgical PCI when assessing peritoneal carcinomatosis or quadrant-specific disease. This approach offers a reliable non-invasive method for evaluating tumour burden in AOC. Full article

Background and Objectives: Epithelial ovarian cancer (EOC) remains the deadliest gynecologic malignancy, yet the psychosocial dynamics of early survivorship are inadequately described. We prospectively quantified six-month trajectories in the quality of life in a consecutive cohort of 88 women newly diagnosed with EOC and explored clinical moderators of change. Methods: Eighty-eight consecutive patients (mean age 59.1 ± 10.7 years) completed the SF-36, WHOQOL-BREF, EORTC QLQ-C30, and 10-item Perceived Stress Scale (PSS-10) at baseline (pre-therapy) and six months after cytoreductive surgery ± platinum-based chemotherapy. Stage (FIGO I–II vs. III–IV) and treatment pathway (primary debulking surgery, neoadjuvant chemotherapy plus interval debulking, chemotherapy only) data were recorded. Results: Global QoL improved significantly (EORTC Global Health +5.9 ± 7.7 points; p < 0.001) while perceived stress declined (ΔPSS −3.6 ± 5.1; p < 0.001). SF-36 Physical Functioning rose 4.7 ± 7.9 points (p < 0.001) and Mental Health 4.4 ± 7.9 points (p = 0.004). The WHOQOL Physical and Psychological domains gained 4.7 ± 7.1 and 4.3 ± 7.4 points, respectively (both p < 0.01). Advanced-stage patients experienced larger stress reductions than early-stage patients (−4.1 ± 2.7 vs. −2.9 ± 2.2; p = 0.028) but comparable QoL gains. Greater stress relief correlated with greater mental-health improvement (r = −0.51) and global-health gains (r = −0.45) (all p < 0.001). Treatment pathway did not significantly influence trajectories. Conclusions: Early survivorship after first-line ovarian-cancer therapy was characterized by the clinically meaningful recovery of physical and emotional functioning together with the moderate alleviation of perceived stress. Improvements were observed irrespective of stage and treatment strategy, suggesting that contemporary multimodal regimens do not inevitably compromise patient-reported outcomes. Our estimates provide preliminary effect sizes that should be validated in multi-center cohorts with longer follow-up. Full article

Background and Objectives: The objective of this review is to evaluate the current evidence regarding hormone treatments for both premenopausal and postmenopausal women with early-stage hormone receptor (HR) positive breast cancer. Materials and Methods: An in-depth exploration of the existing literature was conducted, with landmark clinical trials such as TEXT, SOFT, ATLAS, and aTTom serving as primary references. Results: Through an extensive review of the literature, our findings indicate that for premenopausal women with HR-positive, HER2-negative BC with a low risk of recurrence, standard 5-year monotherapy with tamoxifen represents the optimal therapeutic management, given its favorable clinical outcomes and lower associated toxicity. In contrast, for premenopausal women with an intermediate to high risk of recurrence with the same tumor characteristics, the most effective approach stated in the literature is a combination of ovarian suppression therapy (chemical/surgical) and an aromatase inhibitor/selective estrogen receptor modulator (tamoxifen), with a possible extension of the standard therapeutic period. In postmenopausal patients with HR-positive, HER2-negative breast cancer with a low recurrence risk, the first line of treatment is usually a standard 5-year period of treatment with aromatase inhibitors (AIs)(letrozole, anastrozole, or exemestane). On the other hand, in postmenopausal women with an intermediate to high risk, combination therapy might be needed, as well as an extension of the standard therapeutic time. Conclusions: Treatment consensus depends on pre- vs. postmenopausal status and recurrence risk. Full article

Purpose/Objective(s): Peritoneal carcinosis can occur in several gastrointestinal or gynecological malignancies and its prognosis is usually poor. With the advent of more effective systemic agents, the overall survival of metastatic patients has been revolutionized and isolated peritoneal or abdominal wall metastases might benefit from local treatments; Stereotactic Body Radiotherapy (SBRT) might be considered in selected patients with oligometastatic presentation. Materials/Methods: Oligometastases were defined according to recent ESTRO/EORTC consensus. Inclusion criteria were as follows: ECOG PS ≤ 2, written informed consent, up to five lesions to be treated at the same time, patients treated with radiotherapy schedules applying minimum 6 Gy per fraction. The primary endpoint of the study was local control (LC); acute and late toxicity, distant progression-free survival (DPFS), time-to-next systemic treatment (TNST), polymetastatic-free survival (PMFS) and overall survival (OS) were secondary endpoints. Toxicity was assessed according to CTCAE criteria v5.0. Statistical associations between clinical variables and outcomes were assessed using Fisher’s exact test, and Kruskal–Wallis test, as appropriate. Survival outcomes were estimated using the Kaplan–Meier method and compared using the log-rank test. Results: Between April 2020 and September 2024 a total of 26 oligometastatic lesions located in the peritoneum or in the abdominal wall detected in 20 patients received SBRT with Helical Tomotherapy. All cases have been assessed by a multidisciplinary team. Only in three patients out of twenty did more than one lesion receive SBRT: two lesions in two patients, and five lesions in a single case of colorectal cancer with ongoing third-line systemic treatment. Median total dose was 30 Gy (27–35 Gy) in five fractions (3–5). The most frequent primary neoplasm was ovarian cancer in 14/20, endometrial in 2/20, while the remaining were colorectal, vaginal, pancreatic and non-small cell lung cancer. Four lesions were located in the abdominal wall, while the remaining twenty-two were located in the peritoneum. Concurrent systemic therapy was administered in 18/20 patients. With a median follow-up of 15 months (range, 6–59), our 1-year LC was 100%, while 1-year DPFS, PMFS, TNTS and OS rates were 54%, 69%, 61% and 83%, respectively. Abdominal wall location and treatment of a subsequent oligometastatic recurrence with a second course of SBRT were both significantly associated with improved OS (p = 0.03 and p = 0.04, respectively). No G ≥ 3 adverse events occurred. Conclusion: Our preliminary data support the use of SBRT in selected cases of oligometastatic disease located in the peritoneum or in the abdominal wall with excellent results in terms of tolerability and promising clinical outcomes. Full article

Background/Objectives: The effects of combining chemotherapy with hormonal therapy based on hormone receptor (HR) expression in epithelial ovarian, fallopian tube, or primary peritoneal (EOC) remain unclear. This study evaluated the efficacy and safety of physician-chosen chemotherapy combined with hormonal therapy in patients with heavily pretreated advanced EOC, stratified by HR expression. Methods: This phase II, multicenter, pilot study included patients with heavily pretreated advanced EOC, allocated to estrogen receptor (ER)-dominant or progesterone receptor (PR)-dominant arms. Patients in the ER-dominant arm received tamoxifen plus physician-selected chemotherapy, while those in the PR-dominant arm received megestrol acetate (MA) plus chemotherapy. The primary outcome was the best objective response rate (ORR) for six months, assessed using an optimal two-stage Simon design. Results: Among 33 ER-dominant patients with high-grade serous carcinoma (HGSC), the six-month best ORR was 27.3% (3% complete response, 24.2% partial response). The six-month ORR and clinical benefit rate (CBR) were 18.8% and 37.5%, respectively, with 62.5% experiencing progressive disease (PD). Among three PR-dominant patients (two clear cell carcinoma and one HGSC), the six-month best ORR was 0%. The six-month ORR and CBR were also 0%, and all experienced PD within six months. No unacceptable toxicity related to tamoxifen or MA was encountered. Conclusions: In heavily pretreated advanced HGSC patients with ER-dominant expression, chemotherapy combined with tamoxifen showed encouraging clinical activity with favorable safety. While limited by the study design, these findings suggest a potential role for tailored hormonal therapy combined with chemotherapy based on HR expression in heavily pretreated advanced EOC. Clinical Trial Registration: KCT0004571 Full article

Background: It is crucial to predict the response to chemotherapy and identify prognostic markers for recurrence and survival in patients with epithelial ovarian cancer (EOC), in order to effectively manage patient care. The CA-125 elimination rate constant K (KELIM) has recently been developed as a means of assessing the chemotherapy response and has been tested mainly in patients enrolled in randomized controlled trials. The objective of this study was to investigate whether the KELIM score is a prognostic marker for progression-free survival (PFS) and overall survival (OS) in EOC, utilizing its role in predicting the chemotherapy response in real-life settings. Method: Demographic, surgical, and survival data of patients with EOC operated on in Antalya Training and Research Hospital between January 2015 and December 2021 were obtained from the electronic gynecological oncology clinic database system and analyzed retrospectively. Results: A total of 102 patients with EOC were included; 30 patients (29.4%) had a KELIM score ≥ 1 and 72 (70.6%) patients had a KELIM score < 1. In the group with a KELIM score < 1, recurrence and refractory disease occurred in 49 patients, while it was 11 patients in the group with a KELIM score ≥ 1 (p = 0.004). PFS was 12 months and 32 months in the groups with KELIM scores of <1 and ≥1, respectively (p = 0.012). There was no difference between groups regarding OS (p = 0.139). In the whole group, KELIM score (<1 vs. ≥1) and type of surgery (IDS vs. PDS) were found to be independent prognostic factors for PFS (RR = 0.44; 95%CI: 0.22–0.88; p = 0.021 and RR = 2.97; 95%CI: 1.76–5.01; p < 0.001, respectively). Conclusion: We found that a favorable KELIM score was associated with better PFS in all groups of patients undergoing surgery for EOC in a real-life setting. With the increasing number of studies, the KELIM score will play an important role in providing better guidance to clinicians at the initial presentation of patients and in subsequent treatment planning. Full article

Background/Objectives: Patients with advanced ovarian cancer face a high risk of venous thromboembolism (VTE). This study evaluates the incidence and risk factors for pulmonary thromboembolism (PE) in patients with advanced high-grade serous ovarian carcinoma (HGSOC) undergoing primary treatment, with a focus on personalized risk stratification. Methods: A retrospective analysis was conducted on women with FIGO stage IIIA-IVB HGSOC treated at the University Hospital of Parma between January 2012 and May 2023. All patients underwent CT-based staging prior to primary treatment. When resectability was uncertain, diagnostic laparoscopy and the Fagotti score were performed. Based on cytoreductive potential, patients received either primary debulking surgery (PDS) followed by adjuvant chemotherapy (AC) or neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) and AC. The Khorana score, a thromboembolic risk model, was calculated prior to chemotherapy. Logistic regression was used to assess the association between baseline characteristics and PE. Results: Among 167 HGSOC patients analyzed, 13 (7.8%) experienced PE. Among the 115 patients undergoing diagnostic laparoscopy, each 2-point increase in the Fagotti score above 8 raised PE risk by 76% (OR 1.76, p = 0.006, 95% CI: 1.17–2.63). Patients undergoing NACT-IDS had a significantly higher risk of PE (OR 4.04, 95% CI: 1.19–13.74, p = 0.02) than patients who underwent PDS. A Khorana score of 3 was an independent predictor of PE (OR 37.66, 95% CI: 2.43–582.36, p = 0.009). Conclusions: Based on our results, NACT followed by IDS or a Fagotti score greater than 8 were associated with increased PE risk in HGSOC patients. Khorana score was the strongest predictor of PE in HGSOC patients. Full article

Background/Objectives: Tumor-infiltrating lymphocytes (TILs) and inflammation status are emerging prognostic markers in various cancers, but their significance in high-grade serous ovarian carcinoma (HGSC) remains unclear. Our objective was to evaluate different TIL subtypes and inflammation status in relation to progression-free survival (PFS) in primary HGSC. Methods: CD3⁺/CD4⁺/CD8⁺/PD-1+ stromal TILs (sTILs) and intraepithelial TILs (iTILs) were evaluated by manual assessment and digital image analysis (DIA), following TIL Working Group recommendations. Inflammation status was evaluated through the following scores: systemic immune-inflammation index (SII), pan-immune-inflammation value (PIV), CA125, and lactate dehydrogenase (LDH). Results: CD8⁺ TILs were the most prevalent subtype in both iTILs and sTILs. However, sTILs were significantly more abundant than iTILs (p < 0.001) among all subsets, except for PD-1+ cells. DIA results of TIL assessments were in agreement with manual assessments. High stromal CD3⁺ and CD8⁺ TILs, PIV, CA125, and LDH, were associated with improved PFS. Potential independent prognostic factors for PFS in manual assessment were PIV (HR = 0.32, CI 95% = 0.12–0.82) and CD8⁺ sTILs (HR = 0.30, CI 95% = 0.12–0.79), whereas in DIA assessment they were CD3⁺ sTILs (HR = 0.31, CI 95% = 0.15–0.67), PIV (HR = 0.35, 95% CI 0.13–0.96), and residual disease (HR = 0.21 95% CI 0.08–0.53). Conclusions: CD3⁺/CD8⁺ sTILs and PIV are promising prognostic indicators in HGSC; however, further research is needed to confirm their clinical utility. Full article

Anthracyclines have been clinically well established in cancer chemotherapy for decades. The main limitations of this drug class are the development of resistance and severe side effects. In the present investigation, we analyzed 30 anthracyclines in a panel of 59 cell lines of the National Cancer Institute, USA. The log₁₀IC₅₀ values varied from −10.49 M (3′-deamino-3′-(4″-(3″-cyano)morpholinyl)-doxorubicin, 1) to −4.93 M (N,N-dibenzyldaunorubicin hydrochloride, 30). Multidrug-resistant NCI-ADR-Res ovarian cancer cells revealed a high degree of resistance to established anthracyclines (between 18-fold to idarubicin (4) and 166-fold to doxorubicin (13) compared to parental, drug-sensitive OVCAR8 cells). The resistant cells displayed only low degrees of resistance (1- to 5-fold) to four other anthracyclines (7, 18, 28, 30) and were even hypersensitive (collaterally sensitive) to two compounds (1, 26). Live cell time-lapse microscopy proved the cross-resistance of the three chosen anthracyclines (4, 7, 9) on sensitive CCRF/CEM and multidrug-resistant CEM/ADR5000 cells. Structure–activity relationships showed that the presence of tertiary amino functions is helpful in avoiding resistance, while primary amines rather increased resistance development. An α-aminonitrile function as in compound 1 was favorable. Investigating the mRNA expression of 49 ATP-binding cassette (ABC) transporter genes showed that ABCB1/MDR1 encoding P-glycoprotein was the most important one for acquired and inherent resistance to anthracyclines. Molecular docking demonstrated that all anthracyclines bound to the same binding domain at the inner efflux channel side of P-glycoprotein with high binding affinities. Kaplan–Meier statistics of RNA sequencing data of more than 8000 tumor biopsies of TCGA database revealed that out of 23 tumor entities high ABCB1 expression was significantly correlated with worse survival times for acute myeloid leukemia, multiple myeloma, and hepatocellular carcinoma patients. This indicates that ABCB1 may serve as a prognostic marker in anthracycline-based chemotherapy regimens in these tumor types and a target for the development of novel anthracycline derivatives. Full article