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OBJECTIVE: Treatment of advanced-stage ovarian cancer contains cytoreductive surgery (CRS) and chemotherapy. Achieving successful CRS (≤ 1 cm residual disease) is prognostically important, but may not be feasible peri-operatively while still risking complications. Therefore, patients' treatment expectations are important to discuss. We investigated patient considerations for interval CRS. METHODS: Patients with advanced-stage ovarian cancer planned for interval CRS completed a questionnaire about the impact of chance of successful CRS, survival benefit and becoming care-dependent on decision-making regarding CRS. The questionnaire included a vignette study, in which patients repeatedly chose between two treatment scenarios with varying levels for chance of successful CRS, survival benefit and risk of complications including stoma. Patient preferences were analyzed, including differences between patients aged < 70 and ≥ 70 years. RESULTS: Among 85 included patients, 31 (37%) patients considered interval CRS worthwhile irrespective of survival benefit and 33 (39%) irrespective of chance of successful surgery. However, 34 patients (41%) considered interval CRS only worthwhile if survival benefit was > 12 months, while 41 (49%) thought so if chance of successful surgery was ≥ 25%. Older patients considered these factors more important. Overall, 27% considered becoming permanently dependent of home care unacceptable. In the vignette study (n = 72) risk of complications and stoma were considered less important than chance of successful CRS and survival benefit. CONCLUSION: Survival benefit, chance of successful surgery and becoming care-dependent are important factors in patient's decision for interval CRS, while risk of complications and stoma are less important. Our results are useful in shared decision-making for interval CRS in ovarian cancer.
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Procedimientos Quirúrgicos de Citorreducción , Neoplasias Ováricas , Prioridad del Paciente , Humanos , Femenino , Neoplasias Ováricas/cirugía , Neoplasias Ováricas/patología , Neoplasias Ováricas/psicología , Procedimientos Quirúrgicos de Citorreducción/métodos , Prioridad del Paciente/estadística & datos numéricos , Anciano , Persona de Mediana Edad , Encuestas y Cuestionarios , Adulto , Anciano de 80 o más Años , Estadificación de Neoplasias , Toma de Decisiones , Carcinoma Epitelial de Ovario/cirugía , Carcinoma Epitelial de Ovario/mortalidad , Carcinoma Epitelial de Ovario/patologíaRESUMEN
Endometrial cancer incidence is rising and current diagnostics often require invasive biopsy procedures. DNA methylation marker analysis of minimally- and non-invasive sample types could provide an easy-to-apply and patient-friendly alternative to determine cancer risk. Here, we compared the performance of DNA methylation markers to detect endometrial cancer in urine, cervicovaginal self-samples and clinician-taken cervical scrapes. Paired samples were collected from 103 patients diagnosed with stage I to IV endometrial cancer. Urine and self-samples were collected at home. All samples were tested for nine DNA methylation markers using quantitative methylation-specific PCR. Methylation levels measured in endometrial cancer patients were compared to unpaired samples of 317 healthy controls. Diagnostic performances were evaluated by univariable and multivariable logistic regression analysis, followed by leave-one-out cross-validation. Each methylation marker showed significantly higher methylation levels in all sample types of endometrial cancer patients compared to healthy controls (P < .01). Optimal three-marker combinations demonstrated excellent diagnostic performances with area under the receiver operating curve values of 0.95 (95% CI: 0.92-0.98), 0.94 (0.90-0.97) and 0.97 (0.96-0.99), for endometrial cancer detection in urine, self-samples and scrapes, respectively. Sensitivities ranged from 89% to 93% at specificities of 90% to 92%. Virtually equal performances were obtained after cross-validation and excellent diagnostic performances were maintained for stage I endometrial cancer detection. Our study shows the value of methylation analysis in patient-friendly sample types for endometrial cancer detection of all stages. This approach has great potential to screen patient populations at risk for endometrial cancer.
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Neoplasias Endometriales , Infecciones por Papillomavirus , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Femenino , Humanos , Metilación de ADN , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/patología , Cuello del Útero/patología , Biopsia , Neoplasias Endometriales/diagnóstico , Neoplasias Endometriales/genética , Displasia del Cuello del Útero/diagnóstico , Infecciones por Papillomavirus/diagnósticoRESUMEN
OBJECTIVE: To assess the association between loss of lumbar skeletal muscle mass and density during neoadjuvant chemotherapy (NACT) and postoperative complications after interval cytoreductive surgery (CRS) in older patients with ovarian cancer. MATERIALS AND METHODS: This multicenter, retrospective cohort study included patients aged 70 years and older with primary advanced stage ovarian cancer (International Federation of Gynecology and Obstetrics stage III-IV), treated with NACT and interval CRS. Skeletal muscle mass and density were retrospectively assessed using Skeletal Muscle Index (SMI) and Muscle Attenuation (MA) on routinely made Computed Tomography scans before and after NACT. Loss of skeletal muscle mass or density was defined as >2% decrease per 100 days in SMI or MA during NACT. RESULTS: In total, 111 patients were included. Loss of skeletal muscle density during NACT was associated with developing any postoperative complication ≤30 days after interval CRS both in univariable (Odds Ratio (OR) 3.69; 95% Confidence Interval (CI) 1.57-8.68) and in multivariable analysis adjusted for functional impairment and WHO performance status (OR 3.62; 95%CI 1.27-10.25). Loss of skeletal muscle density was also associated with infectious complications (OR 3.67; 95%CI 1.42-9.52) and unintended discontinuation of adjuvant chemotherapy (OR 5.07; 95%CI 1.41-18.19). Unlike loss of skeletal muscle density, loss of skeletal muscle mass showed no association with postoperative outcomes. CONCLUSION: In older patients with ovarian cancer, loss of skeletal muscle density during NACT is associated with worse postoperative outcomes. These results could add to perioperative risk assessment, guiding the decision to undergo surgery or the need for perioperative interventions.
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Terapia Neoadyuvante , Neoplasias Ováricas , Anciano , Anciano de 80 o más Años , Carcinoma Epitelial de Ovario/cirugía , Quimioterapia Adyuvante/métodos , Procedimientos Quirúrgicos de Citorreducción/métodos , Femenino , Humanos , Músculo Esquelético/diagnóstico por imagen , Terapia Neoadyuvante/métodos , Neoplasias Ováricas/complicaciones , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/cirugía , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Estudios RetrospectivosRESUMEN
OBJECTIVE: To determine the predictive value of lumbar skeletal muscle mass and density for postoperative outcomes in older women with advanced stage ovarian cancer. METHODS: A multicenter, retrospective cohort study was performed in women ≥ 70 years old receiving surgery for primary, advanced stage ovarian cancer. Skeletal muscle mass and density were assessed in axial CT slices on level L3. Low skeletal muscle mass was defined as skeletal muscle index < 38.50 cm2/m2. Low skeletal muscle density was defined as one standard deviation below the mean (muscle attenuation < 22.55 Hounsfield Units). The primary outcome was any postoperative complication ≤ 30 days after surgery. Secondary outcomes included severe complications, infections, delirium, prolonged hospital stay, discharge destination, discontinuation of adjuvant chemotherapy and mortality. RESULTS: In analysis of 213 patients, preoperative low skeletal muscle density was associated with postoperative complications ≤ 30 days after surgery (Odds Ratio (OR) 2.83; 95% Confidence Interval (CI) 1.41-5.67), severe complications (OR 3.01; 95%CI 1.09-8.33), infectious complications (OR 2.79; 95%CI 1.30-5.99) and discharge to a care facility (OR 3.04; 95%CI 1.16-7.93). Preoperative low skeletal muscle mass was only associated with infectious complications (OR 2.32; 95%CI 1.09-4.92). In a multivariable model, low skeletal muscle density was of added predictive value for postoperative complications (OR 2.57; 95%CI 1.21-5.45) to the strongest existing predictor functional impairment (KATZ-ADL ≥ 2). CONCLUSION: Low skeletal muscle density, as a proxy of muscle quality, is associated with poor postoperative outcomes in older patients with advanced stage ovarian cancer. These findings can contribute to postoperative risk assessment and clinical decision making.
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Procedimientos Quirúrgicos de Citorreducción/efectos adversos , Neoplasias Ováricas/cirugía , Complicaciones Posoperatorias/epidemiología , Sarcopenia/epidemiología , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Tiempo de Internación , Músculo Esquelético/diagnóstico por imagen , Estadificación de Neoplasias , Neoplasias Ováricas/complicaciones , Neoplasias Ováricas/diagnóstico , Complicaciones Posoperatorias/etiología , Periodo Preoperatorio , Estudios Retrospectivos , Medición de Riesgo/estadística & datos numéricos , Factores de Riesgo , Sarcopenia/diagnóstico , Sarcopenia/etiología , Tomografía Computarizada por Rayos X/estadística & datos numéricosRESUMEN
BACKGROUND: Approximately 40% of the newly diagnosed patients with advanced ovarian cancer are aged 70 years or older. Standard treatment for advanced disease consists of cytoreductive surgery and combination chemotherapy. In older patients, standard treatment is often withheld or prematurely stopped due to suspected frailty. It remains challenging to distinguish fit elderly patients who can endure standard therapy from frail patients who may benefit from an adapted treatment strategy. As a comprehensive geriatric assessment (CGA) can contribute to the identification of frail patients and improve tailored therapy in this population, screening tests were developed to select those who may benefit from a CGA. However, the use of these geriatric screening tests has rarely been compared with usual clinical care. The GERSOC-trial will evaluate whether geriatric screening in elderly patients with advanced-stage ovarian cancer improves treatment completion and quality of life. METHODS: This pragmatic, cluster randomised controlled trial will be conducted at a minimum of 20 hospitals in the Netherlands. Hospitals are randomly assigned to geriatric screening care (in which a geriatric screening comprised of the G8 questionnaire and the Timed Up and Go test is performed), or care as usual (in which current usual care is continued). A total of 320 patients aged ≥ 70 years with primary, advanced-stage ovarian carcinoma will be included. Patients considered fit on geriatric screening will receive standard treatment; patients who are considered unfit will be referred to a geriatrician for analysis and treatment advice. The primary outcome is the percentage difference in completed standard and adapted therapies between the two study arms. Secondary outcomes include quality of life, cost-effectiveness and survival. DISCUSSION: This trial aims to gather evidence for the use of geriatric screening in treatment decision-making in elderly patients with advanced ovarian cancer. If proven feasible, beneficial and cost-effective, geriatric screening may be implemented in routine clinical practice. TRIAL REGISTRATION: Netherlands Trial Registry, ID: NL6745. Registered on 2 August 2017.
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Carcinoma Epitelial de Ovario/terapia , Evaluación Geriátrica , Estado Nutricional , Neoplasias Ováricas/terapia , Calidad de Vida , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Análisis Costo-Beneficio , Procedimientos Quirúrgicos de Citorreducción , Femenino , Anciano Frágil , Humanos , Estudios Multicéntricos como Asunto , Países Bajos , Ensayos Clínicos Pragmáticos como AsuntoRESUMEN
Although complete debulking surgery for epithelial ovarian cancer (EOC) is more often achieved with interval debulking surgery (IDS) following neoadjuvant chemotherapy (NACT), randomized evidence shows no long-term survival benefit compared to complete primary debulking surgery (PDS). We performed an observational cohort study of patients treated with debulking surgery for advanced EOC to evaluate the prognostic value of residual disease after debulking surgery. All patients treated between 1998 and 2010 in three Dutch referral gynaecological oncology centres were included. The prognostic value of residual disease after surgery for disease specific survival was assessed using Cox-regression analyses. In total, 462 patients underwent NACT-IDS and 227 PDS. Macroscopic residual disease after debulking surgery was an independent prognostic factor for survival in both treatment modalities. Yet, residual tumour less than one centimetre at IDS was associated with a survival benefit of five months compared to leaving residual tumour more than one centimetre, whereas this benefit was not seen after PDS. Leaving residual tumour at IDS is a poor prognostic sign as it is after PDS. The specific prognostic value of residual tumour seems to depend on the clinical setting, as minimal instead of gross residual tumour is associated with improved survival after IDS, but not after PDS.
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The inflammatory response to the presence of Ureaplasma urealyticum or Mycoplasma hominis in the lower genital tract of subfertile men without any signs or symptoms of infection was investigated by measuring the concentrations of interleukin (IL)-6, IL-8, tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) in seminal plasma. Semen samples were collected from 30 culture-positive subfertile males and 23 culture-negative subfertile males. Enzyme-linked immunosorbent assays showed that IL-8 was present in relatively high concentrations (0.12-4.8 ng/ml) in all semen samples investigated. In contrast, the other cytokines were only detectable in 72% (IFN-gamma), 44% (IL-6) and 19% (TNF-gamma) of the samples and were present in relatively low concentrations (1-410 pg/ml). Seminal plasma cytokine concentrations were similar in samples from culture-positive and culture-negative males. These data strongly indicate that the presence of U. urealyticum or M. hominis in the lower genital tract of subfertile males reflects a silent colonisation rather than infection.