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PURPOSE: Cervical cancer is the fourth most common cancer in women worldwide. A successful screening concept for cervical cancer reduces the incidence and mortality of cervical cancer. Quality indicators (QIs) derived from the screening guidelines for cervical cancer and used by the certified dysplasia units and dysplasia consultancies are evaluated in this paper. The aim of this paper is to present the current data from the annual reports of these units and consultancies. METHODS: The results of the basic data and indicators for the audit year 2022 in the gynaecological dysplasia consultancies and units are presented. In 2022, 84 dysplasia consultancies and 42 units were audited. 40 units and 84 consultancies are included in the annual report. QI outcomes for patients treated in certified dysplasia units and dysplasia consultancies are analysed. Median, overall proportion, and standard deviation were calculated for each QI. RESULTS: The indicator year 2021 was analysed, which was audited in 2022 and evaluated in 2023. A total of nine QIs were analysed. Most target goals were met by the 84 certified dysplasia consultancies and by the 40 dysplasia units. The QIs evaluated are implemented to a very high degree. The targets for the three QIs were achieved by both the dysplasia consultancies and the units in at least 95% of the certified centres (QI 1: 100%, QI 2: 95%, QI 3: 100%; QI 1: 100%, QI 2: 97%, QI 3: 100%, respectively). The presentation of patients to the tumour board by the consultancies/units is working; the units are attending the tumour board more regularly than in previous years. Where the target was not met, the auditors issued deviations or reduced the duration of the certificate. The cases are discussed intensively in the sense of an individual case analysis and with the determination of measures on-site. CONCLUSIONS: The targets for the various indicators were largely met by the dysplasia consultancies and units in the 2022 audit year. The certification of gynaecological dysplasia consultancies/units which have to cooperate with certified gynaecological cancer centres, has for the first time ensured the continuity of healthcare from prevention and early diagnosis to treatment of gynaecological cancers.
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Detección Precoz del Cáncer , Garantía de la Calidad de Atención de Salud , Indicadores de Calidad de la Atención de Salud , Neoplasias del Cuello Uterino , Humanos , Femenino , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/prevención & control , Detección Precoz del Cáncer/normas , Displasia del Cuello del Útero/diagnóstico , Displasia del Cuello del Útero/prevención & control , Derivación y ConsultaRESUMEN
PURPOSE: To evaluate the influence of a previous caesarean section on adverse composite maternal and perinatal outcome in women who attempted a trial of labor. METHODS: This historical cohort study analyzed maternal and perinatal outcome in women with otherwise low risk pregnancies at term who underwent a trial of labor after a caesarean section (TOLAC). The primary outcome measure was the adverse composite outcome. Secondary outcome measures were amongst others the caesarean section rate and the mode of vaginal delivery. RESULTS: The adverse composite outcome was more frequently in the previous caesarean section group compared to women with no previous caesarean Sect. (22.3% vs. 15.6%, p < 0.0001). The percentage of caesarean Sect. (15.4% vs. 8.2%, p < 0,0001), uterine rupture (1.0% vs. 0.02%, p < 0.0001), placental abruption (1.1% vs. 0.3%, p = 0.0014), vaginal operative delivery (16.0% vs. 8.6%, p < 0.0001), pH < 7.10 (3.7% vs. 2.5%, p = 0.0151), base excess < -12 (3.2% vs. 2.2%, p = 0.0297), abnormal cardiotocography (22.5% vs. 13.9%, p < 0,0001) and fetal blood analysis (6.2% vs. 2.6%, p < 0.0001) was significantly higher in women with a previous caesarean section. Taking the parity into account, these differences could only been seen in women without a previous vaginal delivery. In parous women with a previous vaginal delivery and a caesarean section in history, the adverse composite did not differ between the groups. Only the rate of pH < 7.1 was higher in women after a caesarean Sect. (4.5% vs. 1.8%, p = 0.0436). CONCLUSION: Trial of labor after caesarean in otherwise low risk pregnancies is associated with a higher rate of complications especially if there is no history of vaginal delivery.
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PURPOSE: To investigate the capacity of chat-generative pre-trained transformer (Chat-GPT) to understand the S2k guideline of the German Society for Gynecology and Obstetrics on intrauterine growth restriction. METHODS: The German-language free Chat-GPT version was used to test the ability of Chat-GPT to understand the definition of small for gestational age and intrauterine growth restriction, to indicate the correct time and place of delivery and to evaluate ist ability to recommend a spontaneous delivery versus a primary caesarean section in accordance with the guideline recommendations. In order to objectively evaluate the suggestions a simple three-color 'traffic light' evaluation system was employed. RESULTS: Almost all Chat-GPT's suggestions in the context of definition of small for gestational age/intrauterine growth restriction as well as correct time of delivery were adequate, whereas more than half of the suggestions made in terms of correct delivery mode needed reformulation or even correction. CONCLUSION: Chat-GPT appears to be a valuable form of artificial intelligence that could be integrated into everyday clinical practice.
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Cervical cancer is the fourth most common cancer in females. Genome-wide association studies (GWASs) have proposed cervical cancer susceptibility variants at the HLA locus on chromosome 6p21. To corroborate these findings and investigate their functional impact in cervical tissues and cell lines, we genotyped nine variants from cervical cancer GWASs (rs17190106, rs535777, rs1056429, rs2763979, rs143954678, rs113937848, rs3117027, rs3130214, and rs9477610) in a German hospital-based series of 1122 invasive cervical cancers, 1408 dysplasias, and 1196 healthy controls. rs17190106, rs1056429 and rs143954678/rs113937848 associated with cervical malignancies overall, while rs17190106 and rs535777 associated specifically with invasive cancer (OR = 0.69, 95% CI = 0.55-0.86, p = 0.001) or adenocarcinomas (OR = 1.63, 95%CI = 1.17-2.27, p = 0.004), respectively. We tested these and one previously genotyped GWAS variant, rs9272117, for potential eQTL effects on 36 gene transcripts at the HLA locus in 280 cervical epithelial tissues. The strongest eQTL pairs were rs9272117 and HLA-DRB6 (p = 1.9x10E-5), rs1056429 and HLA-DRB5 (p = 2.5x10E-4), and rs535777 and HLA-DRB1 (p = 2.7x10E-4). We also identified transcripts that were specifically upregulated (DDX39B, HCP5, HLA-B, LTB, NFKBIL1) or downregulated (HLA-C, HLA-DPB2) in HPV+ or HPV16+ samples. In comparison, treating cervical epithelial cells with proinflammatory cytokine γ-IFN led to a dose-dependent induction of HCP5, HLA-B, HLA-C, HLA-DQB1, HLA-DRB1, HLA-DRB6, and repression of HSPA1L. Taken together, these results identify relevant genes from both the MHC class I and II regions that are inflammation-responsive in cervical epithelium and associate with HPV (HCP5, HLA-B, HLA-C) and/or with genomic cervical cancer risk variants (HLA-DRB1, HLA-DRB6). They may thus constitute important contributors to the immune escape of precancerous cells after HPV-infection.
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Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Polimorfismo de Nucleótido Simple , Neoplasias del Cuello Uterino , Humanos , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/inmunología , Femenino , Genotipo , Estudios de Casos y Controles , Antígenos HLA/genética , Alelos , Persona de Mediana Edad , Adulto , Interferón gamma/genética , Interferón gamma/inmunología , Línea Celular TumoralRESUMEN
BACKGROUND: Both overweight/obesity and a Western lifestyle are associated with a poorer prognosis in women with breast cancer. The primary aim of this analysis was to examine the effect of a telephone-delivered lifestyle intervention program on reducing body weight and waist circumference, decreasing cardiovascular risk factors and improving lifestyle. DESIGN: Data is derived from an open-label, randomized, controlled phase III study that evaluated two chemotherapy regimens and the impact of a 2-year lifestyle intervention on disease-free survival and secondary outcomes in women with intermediate-risk to high-risk breast cancer. Initially, 2292 women with a body mass index (BMI) between 24 and 40 kg/m2 were randomized into one of two arms of the lifestyle intervention study. After accounting for dropout, 1785 participants remained: 776 in the intervention group (IG) who received a telephone-delivered lifestyle intervention supported by mailed materials, and 1009 in the low-level intervention group (LLIG) who received only mailed educational materials with general recommendations for a healthy lifestyle. Body weight, waist circumference, dietary intake, physical activity, and cardiovascular disease risk parameters were measured repeatedly throughout the intervention and a subsequent 2-year follow-up period. Linear mixed models for repeated measures were used to assess differences in study outcomes between the LLIG and IG at each measured time point. RESULTS: IG participants showed a mean weight loss of -2.7 kg (kg) (versus +0.4 kg, LLIG) at 6 months, -2.8 kg (vs. +0.8 kg, LLIG) at 12 months and -1.8 kg at 24 months (versus +0.9 kg, LLIG). Significant between-group differences for weight loss and reduced waist circumference were observed at all time points until the end of the lifestyle intervention (all p-values < 0.0001), including post-intervention. Reduced energy intake and a higher alternate healthy eating index (AHEI) score in the IG was detected during the lifestyle intervention (AHEI at 24 months: IG 49.1% versus LLIG 42.0%, p < 0.001). Modest significant improvements in several cardiovascular risk factors were observed during the intervention, including fasting plasma glucose, HbA1c, systolic and diastolic blood pressure, and lipids. CONCLUSIONS: A mainly telephone-delivered lifestyle intervention program can reduce body weight and waist circumference, improve diet quality, and decrease cardiometabolic risk in women with overweight/obesity and newly diagnosed, human epidermal growth factor receptor 2 (HER2)/neu-negative, intermediate-risk to high-risk breast cancer. Weight loss, reduced waist circumference and improved dietary patterns were maintained for up to two years post-intervention. TRIAL REGISTRATION: The protocol was registered under the EU Clinical Trials Register, https://www.clinicaltrialsregister.eu/, identifier: 2008-005453-38.
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Neoplasias de la Mama , Conductas Relacionadas con la Salud , Circunferencia de la Cintura , Humanos , Femenino , Persona de Mediana Edad , Peso Corporal , Ejercicio Físico , Índice de Masa Corporal , Estilo de Vida , Obesidad/terapia , Adulto , Pérdida de Peso , Anciano , Estilo de Vida Saludable , Enfermedades Cardiovasculares/prevención & control , TeléfonoRESUMEN
Germline mutations in BRCA1 and BRCA2 (gBRCA1/2) are required for a PARP inhibitor therapy in patients with HER2-negative (HER2-) advanced breast cancer (aBC). However, little is known about the prognostic impact of gBRCA1/2 mutations in aBC patients treated with chemotherapy. This study aimed to investigate the frequencies and prognosis of germline and somatic BRCA1/2 mutations in HER2- aBC patients receiving the first chemotherapy in the advanced setting. Patients receiving their first chemotherapy for HER2- aBC were retrospectively selected from the prospective PRAEGNANT registry (NCT02338167). Genotyping of 26 cancer predisposition genes was performed with germline DNA of 471 patients and somatic tumor DNA of 94 patients. Mutation frequencies, progression-free and overall survival (PFS, OS) according to germline mutation status were assessed. gBRCA1/2 mutations were present in 23 patients (4.9%), and 33 patients (7.0%) had mutations in other cancer risk genes. Patients with a gBRCA1/2 mutation had a better OS compared to non-mutation carriers (HR: 0.38; 95%CI: 0.17-0.86). PFS comparison was not statistically significant. Mutations in other risk genes did not affect prognosis. Two somatic BRCA2 mutations were found in 94 patients without gBRCA1/2 mutations. Most frequently somatic mutated genes were TP53 (44.7%), CDH1 (10.6%) and PTEN (6.4%). In conclusion, aBC patients with gBRCA1/2 mutations had a more favorable prognosis under chemotherapy compared to non-mutation carriers. The mutation frequency of ~5% with gBRCA1/2 mutations together with improved outcome indicates that germline genotyping of all metastatic patients for whom a PARP inhibitor therapy is indicated should be considered.
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PURPOSE: The purpose of this study was to evaluate RB1 expression and survival across ovarian carcinoma histotypes and how co-occurrence of BRCA1 or BRCA2 (BRCA) alterations and RB1 loss influences survival in tubo-ovarian high-grade serous carcinoma (HGSC). EXPERIMENTAL DESIGN: RB1 protein expression was classified by immunohistochemistry in ovarian carcinomas of 7,436 patients from the Ovarian Tumor Tissue Analysis consortium. We examined RB1 expression and germline BRCA status in a subset of 1,134 HGSC, and related genotype to overall survival (OS), tumor-infiltrating CD8+ lymphocytes, and transcriptomic subtypes. Using CRISPR-Cas9, we deleted RB1 in HGSC cells with and without BRCA1 alterations to model co-loss with treatment response. We performed whole-genome and transcriptome data analyses on 126 patients with primary HGSC to characterize tumors with concurrent BRCA deficiency and RB1 loss. RESULTS: RB1 loss was associated with longer OS in HGSC but with poorer prognosis in endometrioid ovarian carcinoma. Patients with HGSC harboring both RB1 loss and pathogenic germline BRCA variants had superior OS compared with patients with either alteration alone, and their median OS was three times longer than those without pathogenic BRCA variants and retained RB1 expression (9.3 vs. 3.1 years). Enhanced sensitivity to cisplatin and paclitaxel was seen in BRCA1-altered cells with RB1 knockout. Combined RB1 loss and BRCA deficiency correlated with transcriptional markers of enhanced IFN response, cell-cycle deregulation, and reduced epithelial-mesenchymal transition. CD8+ lymphocytes were most prevalent in BRCA-deficient HGSC with co-loss of RB1. CONCLUSIONS: Co-occurrence of RB1 loss and BRCA deficiency was associated with exceptionally long survival in patients with HGSC, potentially due to better treatment response and immune stimulation.
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Proteína BRCA1 , Proteína BRCA2 , Cistadenocarcinoma Seroso , Neoplasias Ováricas , Proteínas de Unión a Retinoblastoma , Humanos , Femenino , Neoplasias Ováricas/genética , Neoplasias Ováricas/mortalidad , Neoplasias Ováricas/inmunología , Neoplasias Ováricas/patología , Proteína BRCA2/genética , Proteína BRCA2/deficiencia , Proteína BRCA1/genética , Proteína BRCA1/deficiencia , Cistadenocarcinoma Seroso/genética , Cistadenocarcinoma Seroso/patología , Cistadenocarcinoma Seroso/mortalidad , Cistadenocarcinoma Seroso/inmunología , Proteínas de Unión a Retinoblastoma/genética , Pronóstico , Ubiquitina-Proteína Ligasas/genética , Clasificación del Tumor , Linfocitos Infiltrantes de Tumor/inmunología , Linfocitos Infiltrantes de Tumor/metabolismo , Persona de Mediana Edad , Mutación de Línea Germinal , Regulación Neoplásica de la Expresión Génica , Anciano , Biomarcadores de Tumor/genética , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismoRESUMEN
PURPOSE: Implementation science endeavors to facilitate the translation of evidence-based research into clinical routine. The clinical pharmacological/pharmaceutical care program evaluated in the randomized AMBORA trial on medication safety with oral antitumor therapeutics (OAT) optimizes care delivery and provides significant benefits for patients, treatment teams, and health care systems. Thus, we aimed to investigate the implementation of this care program within the AMBORA Competence and Consultation Center (AMBORA Center). METHODS: The AMBORA Center within a University Comprehensive Cancer Center offered several services (eg, patient consultations) and was evaluated according to the RE-AIM framework. This multicenter hybrid type III trial focused on implementation outcomes (eg, patient recruitment, referring units, evaluation of services) while concurrently investigating effectiveness (eg, side effects, medication errors). Quantitative and qualitative assessments were combined. RESULTS: The AMBORA Center conducted over 800 consultations with 420 patients in seven institutions. The primary end point of counseling 70% of patients treated with OAT was not reached. Patients were referred by 15 treatment units compared with 11 units in the AMBORA trial. On the basis of heterogeneous referral rates and characteristics across the institutions, barriers and facilitators of the implementation process were derived. Several survey results (eg, stakeholder interviews, online/paper-based questionnaires) reflected a high appreciation of services by patients and health care professionals. The severity of 60.1% (178 of 296) of detected side effects improved, and 86.3% (297 of 344) of medication errors were resolved. CONCLUSION: Despite not reaching the primary implementation outcome, the AMBORA Center included more treatment units and demonstrated patient benefit of the AMBORA care program by meeting all effectiveness outcomes. We outlined quantitative and qualitative implementation characteristics to enhance outreach and foster further dissemination of centers to optimize medication safety with OAT.
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Antineoplásicos , Humanos , Masculino , Antineoplásicos/uso terapéutico , Antineoplásicos/efectos adversos , Femenino , Administración Oral , Persona de Mediana Edad , Anciano , Derivación y Consulta , Neoplasias/tratamiento farmacológicoRESUMEN
BACKGROUND/AIM: Demographic change and increasing complexity of therapy decisions lead to a growing burden on the healthcare system, necessitating efforts to simplify and enhance the efficiency of patient care. The present study evaluates ChatGPT's ability to provide therapy recommendations for gynecological malignancies that are both in line with the local guidelines and individually tailored to the patient. PATIENTS AND METHODS: Sixteen patients with endometrial, cervical, and ovarian cancer who were treated in the gynecological clinic of the University Hospital Erlangen from January 2022 to August 2023 were included in the analysis. Data collected within clinical routine care were communicated to the chat-based AI model ChatGPT (version 3.5). ChatGPT's performance generating treatment plans were evaluated using an answer scoring system and descriptive analysis. RESULTS: According to the answer scoring system [range: -1 point (minimum) to 2 points (maximum)], ChatGPT demonstrated a good potential in generating therapy recommendations with an average score of 0.75 points for patients with ovarian cancer, 0.7 points for cervical and 1.5 points for endometrial cancer patients. The most common deductions in points were about incomplete therapy recommendations, whereas contraindicated treatment modalities were rarely suggested. Individual patient characteristics were regularly considered by ChatGPT. ChatGPT reliably indicated aftercare and provided detailed information on preventive measures as well as supportive treatment. CONCLUSION: ChatGPT is a promising tool for the generation of therapy suggestions for gynecological carcinomas with high flexibility in response to individual patient differences. At the current state, however, ChatGPT is not suitable for replacing expert panels.
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Neoplasias de los Genitales Femeninos , Adulto , Anciano , Femenino , Humanos , Persona de Mediana Edad , Neoplasias de los Genitales Femeninos/terapia , Medicina de Precisión/métodos , Inteligencia ArtificialRESUMEN
PURPOSE: The receptor activator of nuclear factor kappa B (RANK) and its ligand (RANKL) have been shown to promote proliferation of the breast and breast carcinogenesis. The objective of this analysis was to investigate whether tumor-specific RANK and RANKL expression in patients with primary breast cancer is associated with high percentage mammographic density (PMD), which is a known breast cancer risk factor. METHODS: Immunohistochemical staining of RANK and RANKL was performed in tissue microarrays (TMAs) from primary breast cancer samples of the Bavarian Breast Cancer Cases and Controls (BBCC) study. For RANK and RANKL expression, histochemical scores (H scores) with a cut-off value of > 0 vs 0 were established. PMD was measured in the contralateral, non-diseased breast. Linear regression models with PMD as outcome were calculated using common predictors of PMD (age at breast cancer diagnosis, body mass index (BMI) and parity) and RANK and RANKL H scores. Additionally, Spearman rank correlations (ρ) between PMD and RANK and RANKL H score were performed. RESULTS: In the final cohort of 412 patients, breast cancer-specific RANK and RANKL expression was not associated with PMD (P = 0.68). There was no correlation between PMD and RANK H score (Spearman's ρ = 0.01, P = 0.87) or RANKL H score (Spearman's ρ = 0.04, P = 0.41). RANK expression was highest in triple-negative tumors, followed by HER2-positive, luminal B-like and luminal A-like tumors, while no subtype-specific expression of RANKL was found. CONCLUSION: Results do not provide evidence for an association of RANK and RANKL expression in primary breast cancer with PMD.
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Densidad de la Mama , Neoplasias de la Mama , Ligando RANK , Receptor Activador del Factor Nuclear kappa-B , Humanos , Ligando RANK/metabolismo , Ligando RANK/análisis , Femenino , Receptor Activador del Factor Nuclear kappa-B/metabolismo , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Neoplasias de la Mama/diagnóstico por imagen , Persona de Mediana Edad , Anciano , Adulto , Estudios de Casos y Controles , Inmunohistoquímica , Análisis de Matrices Tisulares , Mama/diagnóstico por imagen , Mama/patología , Mama/metabolismoRESUMEN
PURPOSE: Providing patient access to precision oncology (PO) is a major challenge of clinical oncologists. Here, we provide an easily transferable model from strategic management science to assess the outreach of a cancer center. METHODS: As members of the German WERA alliance, the cancer centers in Würzburg, Erlangen, Regensburg and Augsburg merged care data regarding their geographical impact. Specifically, we examined the provenance of patients from WERA´s molecular tumor boards (MTBs) between 2020 and 2022 (n = 2243). As second dimension, we added the provenance of patients receiving general cancer care by WERA. Clustering our catchment area along these two dimensions set up a four-quadrant matrix consisting of postal code areas with referrals towards WERA. These areas were re-identified on a map of the Federal State of Bavaria. RESULTS: The WERA matrix overlooked an active screening area of 821 postal code areas - representing about 50 % of Bavaria´s spatial expansion and more than six million inhabitants. The WERA matrix identified regions successfully connected to our outreach structures in terms of subsidiarity - with general cancer care mainly performed locally but PO performed in collaboration with WERA. We also detected postal code areas with a potential PO backlog - characterized by high levels of cancer care performed by WERA and low levels or no MTB representation. CONCLUSIONS: The WERA matrix provided a transparent portfolio of postal code areas, which helped assessing the geographical impact of our PO program. We believe that its intuitive principle can easily be transferred to other cancer centers.
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Accesibilidad a los Servicios de Salud , Oncología Médica , Neoplasias , Medicina de Precisión , Humanos , Alemania , Accesibilidad a los Servicios de Salud/organización & administración , Neoplasias/terapia , Oncología Médica/organización & administración , Instituciones Oncológicas/organización & administración , Población RuralRESUMEN
A heuristic tool called "the hallmarks of cancer" helps to reduce the enormous complexity of cancer phenotypes and genotypes to a preliminary set of guiding principles. Other aspects of cancer have surfaced as possible improvements in our understanding of the disease's mechanisms. Endometriosis is a gynecological disease condition negatively impacting the quality of life of many women. To date, there is no curative treatment for endometriosis. Therapy is aimed at treating the symptoms using hormone therapy, pain therapy and complementary therapy. Chronic pain and overlapping pain syndromes and illnesses can also be treated with multimodal pain therapy and psychosomatic therapy. Endometriosis is, however, a chronic and complex entity which, in this regard, resembles cancer. The present work investigates the hallmarks of endometriosis with a view to summarizing the current research status and paving new ways for future research projects.
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The presentation of the results of the prospective randomized international multicenter GCIG INTERLACE trial at the 2023 congress of the European Society of Medical Oncology (ESMO) is likely to change the therapy for locally advanced cervical cancer. In the GCIG INTERLACE trial, six cycles of neoadjuvant chemotherapy administered weekly and consisting of carboplatin AUC2 and paclitaxel 80 mg/m 2 followed by definitive radiochemotherapy with pelvic radiotherapy (40â-â50.4 Gray) and cisplatin (40 mg/m 2 once a week for 5 weeks) and brachytherapy (total dose EQD2 at least 78 Gy at point A) (experimental arm) were compared with definitive radiochemotherapy alone (standard arm) in patients with locally advanced cervical cancer (Fédération Internationale de Gynécologie et d'Obstétrique [FIGO] 2008 stage IB1/node positive, IB2, II, IIIB and IVA) and was found to be significantly superior with significantly longer recurrence-free survival (hazard ratio [HR] 0.65; 95% confidence interval [CI] 0.64â-â0.91; p = 0.013) and significantly longer overall survival rates (HR 0.61; 95% CI: 0.40â-â0.91; p = 0.04) after 5 years' follow-up. After considering the results of the GCIG INTERLACE trial published at the congress, the Uterus Commission of the AGO is of the opinion that neoadjuvant chemotherapy with carboplatin AUC2 and paclitaxel 80 mg/m 2 d1, q7, x6 may be offered to patients with locally advanced cervical cancer (FIGO stage IB1/node positive, IB2, II, IIIB and IVA) in addition to the current standard therapy after the patient has been informed about the risks, with the decision taken on a case-by-case basis. However, before this approach can be discussed at guideline level or defined as the new therapy standard, it will be necessary to wait until the data from the full publication are available.
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Endometriosis constitutes the most common cause of chronic pelvic pain in female patients and is associated with infertility. Although there is no known cause for the disease, it is a heritable condition that is determined by numerous genetic, epigenetic, and environmental aspects. Peroxisome proliferator-activated receptors (PPARs) represent nuclear receptor proteins that control gene expression. By using the MEDLINE and LIVIVO databases we conducted a literature review in order to look into the role of PPARs in the endometriosis pathophysiology and succeeded in revealing 36 pertinent publications between 2001 and 2022. In regards to PPAR expression in endometriosis, PPARγ seems to represent the most studied PPAR isoform in endometriosis and to influence various pathways involved in the disease onset and progression. It's interesting to note that diverse treatment agents targeting the PPAR system have been identified as innovative, effective therapeutic alternatives in the context of endometriosis treatment. In conclusion, PPARs appear to contribute an important role in both endometriosis pathophysiology and therapy.
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Background With more effective therapies for patients with advanced breast cancer (aBC), therapy sequences are becoming increasingly important. However, some patients might drop out of the treatment sequence due to deterioration of their life status. Since little is known about attrition in the real-world setting, this study assessed attrition in the first three therapy lines using a real-world registry. Methods Patients with information available on the first three therapy lines were selected from the German PRAEGNANT registry (NCT02338167). Attrition was determined for each therapy line using competing risk analyses, with the start of the next therapy line or death as endpoints. Additionally, a simple attrition rate was calculated based on the proportion of patients who completed therapy but did not start the next therapy line. Results Competitive risk analyses were performed on 3988 1st line, 2651 2nd line and 1866 3rd line patients. The probabilities of not starting the next therapy line within 5 years after initiation of 1st, 2nd and 3rd line therapy were 30%, 24% and 24% respectively. Patients with HER2-positive disease had the highest risk for attrition, while patients with HRpos/HER2neg disease had the lowest risk. Attrition rates remained similar across molecular subgroups in the different therapy lines. Conclusion Attrition affects a large proportion of patients with aBC, which should be considered when planning novel therapy concepts that specifically address the sequencing of therapies. Taking attrition into account could help understand treatment effects resulting from sequential therapies and might help develop treatment strategies that specifically aim at maintaining quality of life.
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Introduction: The medical and surgical treatment of endometrial cancer (EC) is evolving toward a more patient-centered and personalized approach. The role of laparoscopic sentinel node biopsy (SNB) for early-stage EC is unclear, and very few data are available for atypical endometrial hyperplasia (AEH). The present study investigated the effectiveness of SNB combined with laparoscopic hysterectomy in patients with early-stage EC and AEH. Patients and Methods: This was a retrospective, single-center cohort study for the period from January 2018 to December 2023. A total of 102 patients with atypical hyperplasia (n = 20) and early-stage EC (n = 82) findings on diagnostic curettage underwent pelvic sentinel node biopsy during the final operation. Results: Eleven patients (55%) who had initially been diagnosed with AEH were found to have EC in the final pathology report. No lymph node metastases were detected in patients who had initially been diagnosed with AEH; a 3.6% rate of positive SNBs was found in patients with EC. Changes in tumor grade occurred in 31.3% of the patients and changes in FIGO stage in 33%. Bilateral sentinel node (SN) mapping was successful in 94.1% of the patients. The postoperative outcomes were comparable to those of routine clinical practice without SNB. Conclusions: SNB can be safely offered to patients who have precursor lesions and early-stage EC without notably extending surgical times or increasing postoperative morbidity. This approach can be considered and is safe for patients diagnosed with AEH, but it appears to have a rather small impact on these patients.
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In precision oncology, reliable testing of predictive molecular biomarkers is a prerequisite for optimal patient treatment. Interlaboratory comparisons are a crucial tool to verify diagnostic performance and reproducibility of one's approach. Herein is described the design and results of the first recurrent, internationally performed PIK3CA (phosphatidylinositol-4,5-bisphosphate 3 kinase catalytic subunit α) breast cancer tissue external quality assessment (EQA), organized by German Quality in Pathology GmbH and started in 2021. After the internal pretesting phase performed by the (lead) panel institutes, in both 2021 and 2022, each EQA test set comprised n = 10 tissue samples of hormone receptor-positive, human epidermal growth factor receptor 2-negative invasive breast cancer that had to be analyzed and reported by the participants. In 2021, the results were evaluated separately for German-speaking countries (part 1) and international laboratories (part 2). In 2022, the EQA was performed across the European Union. The EQA success rates were 84.6% (n = 11/13), 88.6% (n = 39/44), and 87.9% (n = 29/33) for EQA 2021 part 1, part 2, and EQA 2022, respectively. The most commonly used methods were next-generation sequencing and mutation-/allele-specific qualitative PCR-based assays. In summary, this recurrent PIK3CA EQA proved to be a suitable approach to obtain an international overview of methods used for PIK3CA mutation analysis, to evaluate them qualitatively, and identify the strengths and weaknesses of individual methods.
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Biomarcadores de Tumor , Neoplasias de la Mama , Fosfatidilinositol 3-Quinasa Clase I , Mutación , Receptor ErbB-2 , Humanos , Fosfatidilinositol 3-Quinasa Clase I/genética , Neoplasias de la Mama/genética , Femenino , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Biomarcadores de Tumor/genética , Receptores de Estrógenos/metabolismo , Receptores de Estrógenos/genética , Reproducibilidad de los Resultados , Receptores de Progesterona/metabolismo , Receptores de Progesterona/genética , Análisis Mutacional de ADN/métodos , Análisis Mutacional de ADN/normasRESUMEN
To identify credible causal risk variants (CCVs) associated with different histotypes of epithelial ovarian cancer (EOC), we performed genome-wide association analysis for 470,825 genotyped and 10,163,797 imputed SNPs in 25,981 EOC cases and 105,724 controls of European origin. We identified five histotype-specific EOC risk regions (p value <5 × 10-8) and confirmed previously reported associations for 27 risk regions. Conditional analyses identified an additional 11 signals independent of the primary signal at six risk regions (p value <10-5). Fine mapping identified 4,008 CCVs in these regions, of which 1,452 CCVs were located in ovarian cancer-related chromatin marks with significant enrichment in active enhancers, active promoters, and active regions for CCVs from each EOC histotype. Transcriptome-wide association and colocalization analyses across histotypes using tissue-specific and cross-tissue datasets identified 86 candidate susceptibility genes in known EOC risk regions and 32 genes in 23 additional genomic regions that may represent novel EOC risk loci (false discovery rate <0.05). Finally, by integrating genome-wide HiChIP interactome analysis with transcriptome-wide association study (TWAS), variant effect predictor, transcription factor ChIP-seq, and motifbreakR data, we identified candidate gene-CCV interactions at each locus. This included risk loci where TWAS identified one or more candidate susceptibility genes (e.g., HOXD-AS2, HOXD8, and HOXD3 at 2q31) and other loci where no candidate gene was identified (e.g., MYC and PVT1 at 8q24) by TWAS. In summary, this study describes a functional framework and provides a greater understanding of the biological significance of risk alleles and candidate gene targets at EOC susceptibility loci identified by a genome-wide association study.
Asunto(s)
Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Neoplasias Ováricas , Polimorfismo de Nucleótido Simple , Humanos , Femenino , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , Carcinoma Epitelial de Ovario/genética , Transcriptoma , Factores de Riesgo , Genómica/métodos , Estudios de Casos y Controles , MultiómicaRESUMEN
PURPOSE: In 2018, the first guideline-based quality indicators (QI) for vulvar cancer were implemented in the data-sheets of certified gynaecological cancer centres. The certification process includes guideline-based QIs as a fundamental component. These indicators are specifically designed to evaluate the level of care provided within the centres. This article aims to give an overview of the developing process of guideline based-QIs for women with vulvar cancer and presents the QIs results from the certified gynaecological cancer centres. METHODS: The QIs were derived in a standardized multiple step process during the update of the 2015 S2k guideline "Diagnosis, Therapy, and Follow-Up Care of Vulvar Cancer and its Precursors" (registry-number: no. 015/059) and are based on strong recommendations. RESULTS: In total, there are eight guideline-based QIs for vulvar cancer. Four QIs are part of the certification process. In the treatment year 2021, 2.466 cases of vulvar cancer were treated in 177 centres. The target values in the centres for pathology reports on tumour resection and lymphadenectomy as well as sentinel lymph nodes have increased since the beginning of the certification process and have been above 90% over the past three treatment years (2019-2021). DISCUSSION: QIs based on strong guideline recommendations, play a crucial role in measuring and allowing to quantify essential aspects of patient care. By utilizing QIs, centres are able to identify areas for process optimization and draw informed conclusions. Over the years the quality of treatment of vulvar cancer patients measured by the QIs was improved. The certification system is continuously reviewed to enhance patient care even further by using the outcomes from QIs revaluation.