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OBJECTIVE: To assess the rate of pathological response rate, and the oncological outcomes of preoperative brachytherapy (PBT) in early-stage cervical cancer. METHODS: A systematic literature review was conducted according to the Preferred Reporting Items for Systematic Reviews and meta-analyses (PRISMA) statement. MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Scopus databases were searched from inception until April 2022. Only English and French articles were included. Studies containing data about pathology response or oncological outcomes among patients who received PBT as compared to those who underwent up-front surgery in early-stage cervical cancer were included. This study was registered in PROSPERO (CRD42022319036). RESULTS: Thirteen studies met the inclusion criteria, 3 randomized controlled trials (RCT), and 10 non-randomized studies (NRS). The 5-year survival was significantly higher in the PBT group compared with the up-front surgery group (OR 1.78, 95% CI 1.11-2.84, I2 = 0%) in the NRS. Recurrence rate was significantly lower in the PBT group compared with in up-front surgery group in the analysis of the RCT but not in NRS, (OR 0.34, 95% CI 0.13-0.91, I2 not applicable) and (OR 0.72, 95% CI 0.26-1.95, I2 = 51%) respectively. PBT was associated with a statistically significant lower rate of positive margins (OR 0.28, 95% CI 0.09-0.89; I2 = 42%) in the RCT and with a significantly higher rate of complete pathology response (CPR) in the RCT analysis (OR 2.55, 95% CI 1.11-5.85, I2 = 0%) and in the NRS (OR 9.64, 95% CI 1.88-49.48, I2 = 76%) compared with the up-front surgery group. CONCLUSION: Preoperative brachytherapy in patients with early-stage cervical cancer could improve pathologic and oncologic outcomes, but it should be assessed in high-quality randomized controlled trials before its implementation in clinical practice.
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Braquiterapia , Neoplasias del Cuello Uterino , Femenino , Humanos , Neoplasias del Cuello Uterino/radioterapia , Neoplasias del Cuello Uterino/cirugíaRESUMEN
BACKGROUND: Management of cervical cancer tumors >2 cm has been a subject of controversy, with management often considered as either up-front radical trachelectomy or neoadjuvant chemotherapy before fertility-sparing surgery. METHODS: A systematic literature review was conducted following the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) checklist. This study was registered in the International Prospective Register of Systematic Reviews (PROSPERO). We searched Medline through PubMed, EMBASE, Cochrane Central Register of Controlled Trials, SCOPUS, and OVID between January 1985 and December 2020. Eligibility criteria for selecting studies were English language, randomized controlled trials, and observational studies including information on fertility and oncologic outcomes. All titles were managed in EndNote X7. Risk of bias was evaluated using the Joanna Briggs Institute (JBI) critical appraisal checklist for observational studies. RESULTS: Twenty-three studies with 205 patients who received neoadjuvant chemotherapy were included. The majority of patients (92.2%, n=189) had stage IB FIGO 2009 cervical cancer. The preferred regimen used was cisplatin in combination with paclitaxel or ifosfamide (80%, n=164). One hundred and eighty patients (87.8%) underwent fertility-sparing surgery; radical vaginal trachelectomy, abdominal trachelectomy, conization, and simple trachelectomy were performed in 62 (34.4%), 49 (27.2%), 34 (18.9%), and 26 (14.4%) women, respectively. In nine patients (5%) the type of procedure was not specified. The follow-up time reported in all studies ranged between 6 and 69 months. In 112 women who sought a pregnancy after surgery, 84.8% (n=95) achieved a gestation.The global recurrence and death rates were 12.8% and 2.8%, respectively. CONCLUSION: Neoadjuvant chemotherapy followed by fertility-sparing surgery is a promising strategy that might allow fertility preservation in highly selected patients with cervical cancer with tumors >2 cm while providing acceptable oncologic outcomes. Results of prospective studies are required to validate its oncological safety. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42020203789.
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Preservación de la Fertilidad/métodos , Terapia Neoadyuvante/métodos , Neoplasias del Cuello Uterino/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Femenino , Humanos , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Selección de Paciente , Embarazo , Traquelectomía/métodos , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/cirugíaRESUMEN
The use of tramadol is a controversial topic in cycling. In order to provide novel evidence on this issue, we tested 29 participants in a pre-loaded cycling time trial (TT; a 20-min TT preceded by 40-min of constant work-rate at 60% of the VO2max) after ingesting 100 mg of tramadol (vs placebo and paracetamol (1.5 g)). Participants performed the Psychomotor Vigilance Task (PVT) at rest and a Sustained Attention to Response Task (SART) during the 60 min of exercise. Oscillatory electroencephalography (EEG) activity was measured throughout the exercise. The results showed higher mean power output during the 20-min TT in the tramadol vs. paracetamol condition, but no reliable difference was reported between tramadol and placebo (nor paracetamol vs. placebo). Tramadol resulted in faster responses in the PVT and higher heart rate during exercise. The main effect of substance was reliable in the SART during the 40-min constant workload (no during the 20-min TT), with slower reaction time, but better accuracy for tramadol and paracetamol than for placebo. This study supports the increased behavioural and neural efficiency at rest for tramadol but not the proposed ergogenic or cognitive (harmful) effect of tramadol (vs. placebo) during self-paced high-intensity cycling.
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Rendimiento Atlético/fisiología , Atención/efectos de los fármacos , Ciclismo/fisiología , Manejo del Dolor/métodos , Tramadol/administración & dosificación , Acetaminofén/administración & dosificación , Adulto , Analgésicos Opioides/administración & dosificación , Método Doble Ciego , Prueba de Esfuerzo , Humanos , Masculino , Adulto JovenRESUMEN
Ovarian cancer is the fifth leading cause of cancer-related deaths. It causes approximately 125,000 deaths per year worldwide; its diagnosis is made in advanced stages resulting in a high mortality rate. The objective of the study was optimizing the isolation of cells obtained from the solid tumor and ascitic fluid of patients with ovarian cancer and the phenotype with markers related to the epithelial-mesenchymal transition. For this, the solid tumor tissue was disaggregated and cultivated with different methodologies. As a result, cell growth was obtained and epi-immunofluorescence was performed using antibodies against E-cadherin, EpCAM, N-cadherin, vimentin, CD133, and CD44. The primary culture from the solid tumor was obtained using Dispase II and DMEM/F12. Finally, heterogeneity was detected in terms of the expression of mesenchymal and epithelial type markers in the two types of isolated cells. Additionally, CD133 and CD44 expression was detected, proteins associated with the tumor stem cells phenotype.
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Biomarcadores de Tumor/análisis , Neoplasias Ováricas/diagnóstico , Vimentina/metabolismo , Cadherinas/metabolismo , Línea Celular Tumoral , Proliferación Celular/fisiología , Transición Epitelial-Mesenquimal/genética , Femenino , Humanos , Células Madre Neoplásicas/patología , Neoplasias Ováricas/patologíaRESUMEN
OBJECTIVE: To review the literature about same-day discharge (SDD) in minimally invasive surgery performed by gynecologic oncologists and identify factors associated with SDD and admission to provide selection criteria. DATA SOURCES: Systematic review of PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and SCOPUS between May 2007 and May 2019. The search included the following medical subject heading terms and keywords: "same day discharge," "patient discharge," "minimally invasive surgical procedures," "hysterectomy," "gynecologic malignancy," "gynecologic neoplasm," "cervical cancer," "ovarian cancer," and "endometrial cancer." METHODS OF STUDY SELECTION: Articles published in English about women who underwent minimally invasive procedures for benign and malignant conditions of the reproductive tract performed by gynecologic oncologists (robotic or laparoscopic) and who received SDD or admission were included. The following were described: SDD and admission rate, readmission or unscheduled evaluation rates within 30 days after surgery, and associated factors for each one. TABULATION, INTEGRATION, AND RESULTS: Nine studies with a total of 16 423 patients were included. The complication rates in the studies were variable, with only 2 studies showing advantages in the SDD group with respect to intraoperative complications and wound complications. There were no statistically significant differences in postoperative complications in the first 30 days after the adoption of SDD. There were no higher readmission rates within the first 30 days in the group of patients who were discharged on the same day vs those admitted. The common factors associated with admission were as follows: age <70 years, surgery after 1 PM, duration of surgery more than 2 hours, and intraoperative complications. Other factors to consider were the presence of comorbidities that require follow-up within the hospital after surgery, adequate postoperative evaluation, and the patient accepting SDD. CONCLUSION: SDD seems to be safe and feasible in minimally invasive surgery performed by gynecologic oncologists. The proposed selection criteria includes the following: younger than 70 years, surgery before 1 PM, procedure less than 2 hours, and no intraoperative complications.
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Neoplasias de los Genitales Femeninos/cirugía , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Alta del Paciente , Selección de Paciente , Adulto , Neoplasias Endometriales/epidemiología , Neoplasias Endometriales/cirugía , Recuperación Mejorada Después de la Cirugía , Femenino , Neoplasias de los Genitales Femeninos/epidemiología , Humanos , Histerectomía/efectos adversos , Histerectomía/métodos , Histerectomía/estadística & datos numéricos , Complicaciones Intraoperatorias/epidemiología , Complicaciones Intraoperatorias/cirugía , Laparoscopía/efectos adversos , Laparoscopía/métodos , Laparoscopía/estadística & datos numéricos , Persona de Mediana Edad , Procedimientos Quirúrgicos Mínimamente Invasivos/efectos adversos , Procedimientos Quirúrgicos Mínimamente Invasivos/estadística & datos numéricos , Oncólogos/estadística & datos numéricos , Alta del Paciente/estadística & datos numéricos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/cirugía , Pautas de la Práctica en Medicina/normas , Pautas de la Práctica en Medicina/estadística & datos numéricos , Procedimientos Quirúrgicos Robotizados/efectos adversos , Procedimientos Quirúrgicos Robotizados/métodos , Procedimientos Quirúrgicos Robotizados/estadística & datos numéricos , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/cirugíaAsunto(s)
Países en Desarrollo , Neoplasias Ováricas , Humanos , Neoplasias Ováricas/terapia , FemeninoRESUMEN
The identification of daily life events that trigger significant changes on our affective state has become a fundamental task in emotional research. To achieve it, the affective states must be assessed in real-time, along with situational information that could contextualize the affective data acquired. However, the objective monitoring of the affective states and the context is still in an early stage. Mobile technologies can help to achieve this task providing immediate and objective data of the users' context and facilitating the assessment of their affective states. Previous works have developed mobile apps for monitoring affective states and context, but they use a fixed methodology which does not allow for making changes based on the progress of the study. This work presents a multimodal platform which leverages the potential of the smartphone sensors and the Experience Sampling Methods (ESM) to provide a continuous monitoring of the affective states and the context in an ubiquitous way. The platform integrates several elements aimed to expedite the real-time management of the ESM questionnaires. In order to show the potential of the platform, and evaluate its usability and its suitability for real-time assessment of affective states, a pilot study has been conducted. The results demonstrate an excellent usability level and a good acceptance from the users and the specialists that conducted the study, and lead to some suggestions for improving the data quality of mobile context-aware ESM-based systems.
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Afecto , Telemedicina/métodos , Adolescente , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Teléfono Inteligente , Encuestas y Cuestionarios , Adulto JovenRESUMEN
Extant evidence suggests that acute exercise triggers a tonic power increase in the alpha frequency band at frontal locations, which has been linked to benefits in cognitive function. However, recent literature has questioned such a selective effect on a particular frequency band, indicating a rather overall power increase across the entire frequency spectrum. Moreover, the nature of task-evoked oscillatory brain activity associated to inhibitory control after exercising, and the duration of the exercise effect, are not yet clear. Here, we investigate for the first time steady state oscillatory brain activity during and following an acute bout of aerobic exercise at two different exercise intensities (moderate-to-high and light), by means of a data-driven cluster-based approach to describe the spatio-temporal distribution of exercise-induced effects on brain function without prior assumptions on any frequency range or site of interest. We also assess the transient oscillatory brain activity elicited by stimulus presentation, as well as behavioural performance, in two inhibitory control (flanker) tasks, one performed after a short delay following the physical exercise and another completed after a rest period of 15' post-exercise to explore the time course of exercise-induced changes on brain function and cognitive performance. The results show that oscillatory brain activity increases during exercise compared to the resting state, and that this increase is higher during the moderate-to-high intensity exercise with respect to the light intensity exercise. In addition, our results show that the global pattern of increased oscillatory brain activity is not specific to any concrete surface localization in slow frequencies, while in faster frequencies this effect is located in parieto-occipital sites. Notably, the exercise-induced increase in oscillatory brain activity disappears immediately after the end of the exercise bout. Neither transient (event-related) oscillatory activity, nor behavioural performance during the flanker tasks following exercise showed significant between-intensity differences. The present findings help elucidate the effect of physical exercise on oscillatory brain activity and challenge previous research suggesting improved inhibitory control following moderate-to-high acute exercise.
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Ondas Encefálicas/fisiología , Encéfalo/fisiología , Electroencefalografía/métodos , Función Ejecutiva/fisiología , Ejercicio Físico/fisiología , Inhibición Psicológica , Desempeño Psicomotor/fisiología , Adulto , Humanos , Masculino , Adulto JovenRESUMEN
OBJECTIVE: The goal of this study is to identify predictive factors in patients with a diagnosis of early-stage cervical cancer after simple hysterectomy in order to avoid a radical parametrectomy. METHODS: A retrospective review was performed of all patients who underwent radical parametrectomy and bilateral pelvic lymphadenectomy at MD Anderson Cancer Center and at the Instituto de Cancerologia Las Americas in Medellin, Colombia from December 1999 to September 2017. We sought to determine the outcomes in patients diagnosed with low-risk factors (squamous, adenocarcinoma or adenosquamous lesions<2cm in size, and invading<10mm) undergoing radical parametrectomy and pelvic lymphadenectomy. RESULTS: A total of 30 patients were included in the study. The median age was 40.4years (range; 26-60) and median body mass index (BMI) was 26.4kg/m2 (range; 17.7-40.0). A total 22 patients had tumors<1cm and 8 had tumors between 1 and 2cm. A total of 6 (33%) of 18 patients had evidence of lymph-vascular invasion (LVSI). No radical parametrectomy specimen had residual tumor, involvement of the parametrium, vaginal margin positivity, or lymph node metastasis. None of the patients received adjuvant therapy. After a median follow-up of 99months (range; 6-160) only one patient recurred. CONCLUSION: Radical parametrectomy may be avoided in patients with low-risk early-stage cervical cancer detected after a simple hysterectomy. Rates of residual disease (parametrial or vaginal) and the need for adjuvant treatments or recurrences are very low.
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Neoplasias del Cuello Uterino/cirugía , Adulto , Femenino , Procedimientos Quirúrgicos Ginecológicos/métodos , Humanos , Histerectomía/métodos , Metástasis Linfática , Persona de Mediana Edad , Estadificación de Neoplasias , Estudios Retrospectivos , Factores de Riesgo , Neoplasias del Cuello Uterino/patologíaRESUMEN
This study analyzed high-density event-related potentials (ERPs) within an electrical neuroimaging framework to provide insights regarding the interaction between multisensory processes and stimulus probabilities. Specifically, we identified the spatiotemporal brain mechanisms by which the proportion of temporally congruent and task-irrelevant auditory information influences stimulus processing during a visual duration discrimination task. The spatial position (top/bottom) of the visual stimulus was indicative of how frequently the visual and auditory stimuli would be congruent in their duration (i.e., context of congruence). Stronger influences of irrelevant sound were observed when contexts associated with a high proportion of auditory-visual congruence repeated and also when contexts associated with a low proportion of congruence switched. Context of congruence and context transition resulted in weaker brain responses at 228 to 257 ms poststimulus to conditions giving rise to larger behavioral cross-modal interactions. Importantly, a control oddball task revealed that both congruent and incongruent audiovisual stimuli triggered equivalent non-linear multisensory interactions when congruence was not a relevant dimension. Collectively, these results are well explained by statistical learning, which links a particular context (here: a spatial location) with a certain level of top-down attentional control that further modulates cross-modal interactions based on whether a particular context repeated or changed. The current findings shed new light on the importance of context-based control over multisensory processing, whose influences multiplex across finer and broader time scales.
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Atención/fisiología , Percepción Auditiva/fisiología , Encéfalo/fisiología , Potenciales Evocados/fisiología , Percepción Visual/fisiología , Estimulación Acústica , Adolescente , Adulto , Análisis de Varianza , Mapeo Encefálico , Electroencefalografía , Femenino , Humanos , Masculino , Dinámicas no Lineales , Estimulación Luminosa , Tiempo de Reacción/fisiología , Adulto JovenRESUMEN
The ability of attention to apply in a flexible manner to several types of information at various stages of processing has been studied extensively. However, the susceptibility of these effects to the nature of the idiosyncratic items being attended is less understood. In the current study, we used symbolic cues to orient the attention of participants to the subsequent appearance of the face of a famous person (the former king of Spain) or an unfamiliar face. These were matched in perceptual characteristics. Behavioral effects showed that face-specific attention optimized response speed in an orthogonal task when the target matched the cue (valid trials) compared to when it did not (invalid trials). According to topographical analyses of the electrophysiological data, the famous and unfamiliar faces engaged dissociable brain circuits in two different temporal windows, from 144 to 300 ms after target processing, and at a later 456-492 ms epoch. In addition, orienting attention to specific faces modulated the perceptual stages reflected in the P1 and N170 potentials but with a different laterality pattern that depended on the familiarity of the faces. Whereas only attention to the famous face enhanced the P1 potential at left posterior electrodes, with no corresponding effect for the unfamiliar face at this stage, the N170 was modulated at left posterior sites for the famous item and at right homologous electrodes for the unfamiliar face. Intermediate processing stages, previously linked to facial identity processing indexed by the P2 and N2 potentials, reflected item familiarity but were not affected by the cueing manipulation. At the P3 level, attention influenced again item processing but did so in an equivalent manner for the famous and unfamiliar face. Our results, showing that identity-specific attention modulates perceptual stages of facial processing at different locations depending on idiosyncratic stimulus familiarity, may inform comparison of studies employing items with different degrees of novelty.
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Atención/fisiología , Potenciales Evocados Visuales/fisiología , Cara , Identificación Psicológica , Reconocimiento Visual de Modelos/fisiología , Adolescente , Adulto , Análisis de Varianza , Señales (Psicología) , Electroencefalografía , Femenino , Humanos , Masculino , Reconocimiento en Psicología , Factores de Tiempo , Adulto JovenRESUMEN
High-density electroencephalographic recordings were used to investigate the level of analysis at which attentional expectations modulate the processing of specific stimuli from the same perceptual category but differentiated in terms of a particular non-perceptual feature: body ownership. We used a task in which colour cues predicted whether a picture of a hand stimulus belonged to the participant or to somebody else. Participants were instructed to respond whether the target was a left or a right hand. Results revealed that the ERP pattern depended on stimulus ownership and attention orienting, which influenced the visual processing of own and someone else's hands differentially. Larger amplitude for others' than for own hands was shown at the N1 deflection (at the right hemisphere). Attentional effects were found at the P2 and P3 potentials. The P2 reflected an interaction between stimulus ownership and attentional orienting, due to a larger validity effect for others' hands. At the P3 level, the data showed a significant validity effect only for self-hand stimuli. In sum, our results suggest that (1) differences as a function of stimulus ownership can be detected at early levels of stimulus processing; (2) endogenous attention can be directed to exemplars within the same category, hand stimuli in this case; (3) the effects of attention are modulated by ownership.
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Atención/fisiología , Electroencefalografía/métodos , Potenciales Evocados/fisiología , Reconocimiento Visual de Modelos/fisiología , Desempeño Psicomotor/fisiología , Adulto , Imagen Corporal , Femenino , Mano , Humanos , Masculino , Adulto JovenRESUMEN
The abrupt onset of a visual stimulus typically results in overt attentional capture, which can be quantified by saccadic eye movements. Here, we tested whether attentional capture following onset of task-irrelevant visual stimuli (new object) is reduced after a bout of intense physical exercise. A group of participants performed a visual search task in two different activity conditions: rest, without any prior effort, and effort, immediately after an acute bout of intense exercise. The results showed that participants exhibited (1) slower reaction time of the first saccade toward the target when a new object was simultaneously presented in the visual field, but only in the rest activity condition, and (2) more saccades to the new object in the rest activity condition than in the effort activity condition. We suggest that immediately after an acute bout of effort, participants improved their ability to inhibit irrelevant (distracting) stimuli.
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Atención/fisiología , Ejercicio Físico/fisiología , Movimientos Oculares/fisiología , Reconocimiento Visual de Modelos/fisiología , Desempeño Psicomotor/fisiología , Adulto , Femenino , Humanos , Masculino , Adulto JovenRESUMEN
Concepts such as "neurodoping" have contributed to an expansion in the area of transcranial direct current stimulation (tDCS) and its impact over physical performance in recent years. This umbrella review examines meta-analyses to evaluate tDCS's impact on exercise performance in healthy individuals. We identified 9 meta-analyses that met our inclusion criteria, encompassing 50 crossover studies and 683 participants. Like previous meta-analyses, we found a small but significant effect across individual studies (gz = 0.28, 95%CI [0.18, 0.39]). However, we also found clear evidence of publication bias, low power and substantial variability in methodological decisions. The average effect became non-significant after accounting for publication bias (grm = 0.10, 95%CrI [-0.04, 0.20], BF10 = 0.99), and a specification curve analysis showed that the final effect could range from g = -0.23 to g = 0.33, depending on decisions such as the formula used for estimating the effect size and multiple additional analytic steps. Overall, our findings suggest that current evidence does not conclusively support acute tDCS as an exercise performance enhancer.
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Rendimiento Atlético , Estimulación Transcraneal de Corriente Directa , Humanos , Rendimiento Atlético/fisiología , Encéfalo/fisiología , Metaanálisis como AsuntoRESUMEN
Throughout the day, humans show natural fluctuations in arousal that impact cognitive function. To study the behavioural dynamics of cognitive control during high and low arousal states, healthy participants performed an auditory conflict task during high-intensity physical exercise (N = 39) or drowsiness (N = 33). In line with the pre-registered hypotheses, conflict and conflict adaptation effects were preserved during both altered arousal states. Overall task performance was markedly poorer during low arousal, but not for high arousal. Modelling behavioural dynamics with drift diffusion analysis revealed evidence accumulation and non-decision time decelerated, and decisional boundaries became wider during low arousal, whereas high arousal was unexpectedly associated with a decrease in the interference of task-irrelevant information processing. These findings show how arousal differentially modulates cognitive control at both sides of normal alertness, and further validate drowsiness and physical exercise as key experimental models to disentangle the interaction between physiological fluctuations on cognitive dynamics.
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Cardiac interoception, the ability to sense and process cardiac afferent signals, has been shown to improve after a single session of acute physical exercise. However, it remains unclear whether repetitive engagement in physical exercise over time leads to long-term changes in cardiac interoceptive accuracy. It is also unknown whether those changes affect the neural activity associated with the processing of afferent cardiac signals, assessed by the heart-evoked potential (HEP). In this study, we aimed to investigate this hypothesis through two cross-sectional studies, categorizing participants as active or inactive based on physical fitness (Study I; N = 45) or self-reported physical activity levels (Study II; N = 60). Interoception was assessed at rest using the HEP (Studies I and II), the Heartbeat Counting task (Study II), and the Rubber Hand Illusion (RHI) (Study II). Study I showed strong evidence of better cardiovascular fitness in the active group than in the inactive group as well as robust between-group differences in electrocardiogram (ECG) recordings. Study 2 replicated the clear differences in ECG as a function of regular physical activity. Those results were expected due to clear differences in physical activity habits. In contrast, our analysis revealed no robust differences between groups across cardiac interoception tasks and the RHI, although the direct relevance of these measures to interoception remains under investigation. In sum, our results do not provide convincing evidence to support a strong version of the notion that regular physical exercise is associated with an enhanced in cardiac interoception.
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Electrocardiografía , Ejercicio Físico , Frecuencia Cardíaca , Interocepción , Humanos , Interocepción/fisiología , Masculino , Femenino , Ejercicio Físico/fisiología , Estudios Transversales , Adulto , Adulto Joven , Frecuencia Cardíaca/fisiología , Corazón/fisiología , Potenciales Evocados/fisiología , ElectroencefalografíaRESUMEN
Introduction and objective: The approach to patients with advanced or metastatic high-grade epithelial ovarian cancer (EOC) has evolved over time with the advent of new therapies and multimodal strategies. The objective of this consensus of experts is to generate national recommendations for the profiling and management of advanced or metastatic high-grade OEC, defined as stages III and IV of the "The International Federation of Gynecology and Obstetrics (FIGO) classification at the time of diagnosis to base on the literature review that included international evidence-based clinical practice guidelines (CPG). Material and methods: Eleven panelists (oncologists and gynecological oncologists) answered 8 questions about the profiling and management of advanced or metastatic ovarian epithelial carcinoma. The panelists were chosen for their academic profile and influence in national health institutions. Guidelines from the "ESMO Standardized Operating Procedures Consensus Conference" were used to develop the consensus. It was agreed that the level of agreement to accept a recommendation should be ≥ 80%. The document was peer reviewed. Results: Eight general recommendations are made, which are presented into five domains. Some of these recommendations are subdivided into specific recommendations. Initial treatment Recommendation 1.1 Complete primary cytoreduction (PCS) surgery is suggested as the initial therapy of choice for patients with high-grade or metastatic EOC, which should ideally be carried out in centers with experience, followed by adjuvant therapy. 1.2 Neoadjuvant chemotherapy followed by interval cytoreduction surgery (ICS) is suggested in those who are unlikely to achieve a complete cytoreduction in PCS either due to unresectable metastatic disease or who present unresectability criteria (imaging, laparoscopic and/or by laparotomy) and that have been defined by a gynecological oncologist and patients with poor functional status and comorbidities according to the criteria of the multidisciplinary team (clinical oncology, gynecological oncology, radiology, etc.). Recommendation 2. In patients with high-grade epithelial ovarian cancer (EOC), in stage III locally advanced or metastatic, who received neoadjuvant chemotherapy and achieved a complete or partial response (cytoreduction with tumor residue < 2.5 mm), the use of Hyperthermic IntraPeritoneal Chemotherapy (HIPEC) could be considered as an alternative to standard platinum-based adjuvant intravenous chemotherapy during interval cytoreductive surgery, after discussion in a multidisciplinary tumor board, at a center experienced in treating this type of patients. Use of genetic testing. Recommendation 3. It is suggested at the time of diagnosis to offer molecular genetic testing to all patients with high-grade advanced or metastatic EOC regardless of family history. Recommendation 4. It is suggested to offer genetic counseling, by qualified personnel, to all patients with high-grade advanced or metastatic EOC who are ordered genetic testing. Recommendation 5. It is suggested that all patients with advanced or metastatic high-grade EOC undergo a germ panel that includes the Breast Cancer Susceptibility Genes 1/2 genes (BRCA 1/2) and the other susceptibility genes according to with institutional protocols and the availability of genetic testing panels; If it is negative, then somatic testing should be performed that includes the homologous recombination deficiency (HRD) status, regardless of family history. Adjuvant Therapy Recommendation 6. 6.1. It is suggested that all patients with advanced stage III/IV EOC, with PSC of (0-2), got adjuvant intravenous chemotherapy as standard treatment within six weeks after Prc. It is suggested paclitaxel/carboplatin. Recommendation 6.2. It is suggested to use standard chemotherapy base on platinum plus Bevacizumab as adjuvant chemotherapy to patients with high-risk disease (EOC stage IV or stage III with suboptimal tumor cytoreduction), following by bevacizumab as maintenance. The use of bevacizumab as maintenance therapy is not recommended if bevacizumab was not included in the first line of treatment. We suggested the dose used in GOG-0218 and ICON7 trials. Recommendation 6.3 It is suggested combined intravenous/intraperitoneal chemotherapy only for selected patients, with optimal cytoreduction (residual lesions < 1 cm), especially those without residual disease (R0) and who are evaluated in a multidisciplinary meeting. It is not considered standard treatment. Recommendation 6.4. 6.4.1 It is suggested to use Poly ADP ribose polymerase (PARP) inhibitors such as olaparib or niraparib as maintenance after receiving first-line chemotherapy in patients with stage III/IV BRCA1/2 positive EOC who received platinumbased chemotherapy and obtained complete response/partial response (CR/PR), 6.4.2 It is suggested to use olaparib alone or in combination with bevacizumab or niraparib in patients with stage III/IV BRCA1/2 positive EOC who received platinum-based chemotherapy plus bevacizumab and achieved CR/PR. 6.4.3 It is suggested to use niraparibin patients with stage III/IV BRCA1/2 negative or unknown EOC who received platinum-based chemotherapy and achieved CR/PR. 6.4.4 It is suggested to use bevacizumab or olaparib plus bevacizumab in patients with EOC stage III/IV BRCA1/2 negative or unknown (HRD positive) who received platinum-based chemotherapy plus bevacizumab and obtained CR/PR. Treatment of disease relapse Recommendation 7. Secondary cytoreductive surgery followed by chemotherapy is suggested for selected patients with high-grade advanced EOC in first relapse, platinum-sensitive (platinum-free interval ≥ 6 months), positive "Arbeitsgemeinschaft Gynäkologische Onkologie AGO" score or "I-model" positive (< 4.7) with a potential resection to R0 in centers with access to optimal surgical and postoperative support. Note: Platinum-free interval and AGO score have only been developed as positive predictors of complete resection and not to exclude patients from surgery. Recommendation 8. 8.1 For patients with relapse advanced high-grade EOC platinum-sensitive, the following is suggested: Platinum-based combination chemotherapy: carboplatin/liposomal doxorubicin or carboplatin/paclitaxel or carboplatin/nab-paclitaxel or carboplatin/docetaxel or carboplatin/gemcitabine) for six cycles. If combination therapy is not tolerated, give carboplatin or cisplatin alone. Combination chemotherapy (carboplatin/gemcitabine or carboplatin/paclitaxel or carboplatin/doxorubicin liposomal) plus bevacizumab followed by bevacizumab as maintenance (until progression or toxicity). Recommendation 8.2 For patients with relapsed advanced high-grade EOC platinum-resistant, it is suggested: Sequential treatment with chemotherapy, preferably with a non-platinum single agent (weekly paclitaxel or pegylated liposomal doxorubicin or docetaxel or oral etoposide or gemcitabine or trabectidine or, topotecan). Weekly paclitaxel or pegylated liposomal doxorubicin or topotecan could be administrate with or without bevacizumab. Other agents are considered potentially active (capecitabine, cyclophosphamide, ifosfamide, irinotecan, oxaliplatin, pemetrexed, vinorelbine, cyclophosphamide) could be recommended for later lines. Hormone receptor-positive patients who do not tolerate or have no response to cytotoxic regimens may receive hormone therapy with tamoxifen or other agents, including aromatase inhibitors (anastrozole and letrozole) or leuprolide acetate, or megestrol acetate. Patients with a performance score ≥ 3 should be considered only for best supportive care. Recommendation 8.3 Maintenance therapy with PARP inhibitors: It is suggested in patients with relapse advanced high-grade EOC stage III/IV BRCA1/2 (positive, negative or unknown) who have received two or more lines of platinum-based chemotherapy and have achieved CR/PR, use olaparib, niraparib or rucaparib. Niraparib could be useful in BRCA 1/2 +/-/unknown patients, as rucaparib, however, the latter does not yet have approval from the regulatory office in Colombia. Conclusions: It is expected that the recommendations issued in this consensus will contribute to improving clinical care, oncological impact, and quality of life of these women.
Introducción y objetivo: el abordaje de pacientes con cáncer epitelial de ovario (CEO) de alto grado avanzado o metastásico ha ido evolucionando a través del tiempo con el advenimiento de nuevas terapias y estrategias multimodales. El objetivo de este consenso de expertos es generar recomendaciones nacionales para el perfilamiento y manejo del CEO de alto grado avanzado o metastásico, definido como estadios III y IV de la clasificación de la Federación Internacional de Ginecología y Obstetricia (FIGO) al momento del diagnóstico, a partir de la revisión de la literatura que incluyó guías de práctica clínica (GPC) internacionales basadas en la evidencia. Materiales y métodos: once panelistas (oncólogos y ginecólogos oncólogos) respondieron ocho preguntas sobre el perfilamiento y manejo del carcinoma epitelial de ovario avanzado o metastásico. Los panelistas fueron escogidos por su perfil académico e influencia en instituciones de salud nacionales. Para el desarrollo del consenso se utilizaron los lineamientos de la "Conferencia de consenso de procedimientos operativos estandarizados de ESMO". Se definió que el nivel de acuerdo para aceptar una recomendación debía ser ≥ 80%. El documento fue revisado por pares. Resultados: Se hacen 8 recomendaciones generales, presentadas en cinco dominios; algunas de ellas se subdividen en recomendaciones específicas. Tratamiento inicial Recomendación 1 1.1. Como terapia inicial de elección para pacientes con CEO de alto grado o metastásico se sugiere la cirugía de citorreducción primaria (Cpr) completa que, idealmente, debe realizarse en centros con experiencia, seguida de terapia adyuvante. 1.2. Se sugiere quimioterapia neoadyuvante seguida de cirugía de citorreducción de intervalo (Cint) en quienes sea improbable alcanzar una citorreducción completa en la Cpr, bien sea por enfermedad metastásica no resecable o que presenten criterios de irresecabilidad (imagenológicos, laparoscópicos o por laparotomía) que hayan sido definidos por un ginecólogo oncólogo. También en pacientes con un pobre estado funcional y comorbilidades de acuerdo con el criterio del equipo multidisciplinario (oncología clínica, ginecología oncológica, radiología, etc.). Recomendación 2. En pacientes con CEO de alto grado, en estadio III localmente avanzado o metastásico, que recibieron quimioterapia neoadyuvante y alcanzaron respuesta completa o parcial (citorreducción con residuo tumoral < 2,5 mm), se podría evaluar el uso de la quimioterapia intraperitoneal hipertérmica (Hyperthermic IntraPeritoneal Chemotherapy - HIPEC) como alternativa a la quimioterapia IV adyuvante estándar basada en platinos durante la Cint, previa discusión en junta multidisciplinaria, en un centro de experiencia en este tipo de pacientes. Uso de pruebas genéticas Recomendación 3. Al momento del diagnóstico, se sugiere ofrecer testeo molecular genético a toda paciente con CEO de alto grado avanzado o metastásico, independientemente de la historia familiar. Recomendación 4. Se sugiere ofrecer asesoramiento genético, por parte de personal calificado, a toda paciente con CEO de alto grado avanzado o metastásico a quien se le ordene un testeo genético. Recomendación 5. Se sugiere que a toda paciente con CEO de alto grado avanzado o metastásico se le realice panel germinal que incluya los genes de susceptibilidad al cáncer de mama 1/2 (BRCA 1/2) y los otros genes de susceptibilidad de acuerdo con los protocolos institucionales y la disponibilidad de paneles de testeo genético; si es negativo entonces se debería realizar testeo somático que incluya el estatus de deficiencia de la recombinación homóloga (homologous recombination deficiency - HRD), independientemente de la historia familiar. Terapia adyuvante Recomendación 6 6.1. Se sugiere que a toda paciente con CEO estadios III/IV avanzado o metastásico, con estatus de desempeño (performance score care - PSC) de 0-2 se le administre como tratamiento estándar quimioterapia intravenosa (IV) adyuvante dentro de las seis semanas posteriores a la Cpr. Se sugiere administrar paclitaxel/carboplatino. 6.2. Se sugiere utilizar quimioterapia estándar basada en platino más bevacizumab como adyuvancia en pacientes con enfermedad de alto riesgo (CEO estadios IV o III con citorreducción tumoral subóptima), continuando con bevacizumab como mantenimiento. No se recomienda el uso de bevacizumab como terapia de mantenimiento si no se incluyó en la primera línea de tratamiento. Se sugiere seguir los esquemas de los estudios Gynecologic Oncology Group Study (GOG-0218) e International Collaborative Ovarian Neoplasm (ICON7). 6.3. Se sugiere la quimioterapia combinada IV/intraperitoneal (IP) solo para pacientes seleccionadas, con una citorreducción óptima (lesiones residuales < 1 cm), en especial aquellas sin enfermedad residual (R0) y que sean evaluadas en junta multidisciplinaria. La quimioterapia combinada IV/IP no se considera como tratamiento estándar. 6.4. 6.4.1. Se sugiere utilizar inhibidores de poli(ADP-ribosa) polimerasa (PARP) tales como olaparib o niraparib como mantenimiento después de recibir una primera línea de quimioterapia en pacientes con CEO estadios III/IV BRCA1/2 positivo que recibieron quimioterapia basada en platino y obtuvieron respuesta completa/respuesta parcial (RC/RP). 6.4.2. Se sugiere utilizar olaparib solo o en combinación con bevacizumab o niraparib en pacientes con CEO estadios III/IV BRCA1/2 positivo que recibieron quimioterapia basada en platino más bevacizumab y obtuvieron RC/RP. 6.4.3. Se sugiere utilizar niraparib en pacientes con CEO estadio III/IV BRCA1/2 negativo o desconocido que recibieron quimioterapia basada en platino y obtuvieron RC/RP. 6.4.4. Se sugiere utilizar bevacizumab u olaparib más bevacizumab en pacientes con CEO estadios III/IV BRCA1/2 negativo o desconocido (HRD positivo) que recibieron quimioterapia basada en platino más bevacizumab y obtuvieron RC/RP. Tratamiento de la recaída de la enfermedad Recomendación 7. Se sugiere la realización de la cirugía de citorreducción secundaria (Csec), seguida de quimioterapia, a pacientes seleccionadas con CEO de alto grado avanzado o metastásico en primera recaída, platino-sensibles (intervalo libre de platinos ≥ 6 meses), puntuación Arbeitsgemeinschaft Gynäkologische Onkologie (AGO) positiva o Integrate model (I-Model) positivo (< 4,7), y con una potencial resección a R0, en centros con acceso a soporte quirúrgico y posoperatorio óptimo. Nota: el intervalo libre de tratamiento con platinos y la puntuación AGO solo se han desarrollado como predictores positivos de resección completa y no para excluir a las pacientes de la cirugía. Recomendación 8 8.1. Para pacientes con CEO de alto grado avanzado o metastásico en recaída platino-sensibles se sugiere: Quimioterapia combinada basada en platino: carboplatino/doxorrubicina liposomal o carboplatino/paclitaxel o carboplatino/ nab-paclitaxel o carboplatino/docetaxel o carboplatino/gemcitabina, por seis ciclos. Si no se tolera la terapia combinada, dar carboplatino o cisplatino solo. Quimioterapia combinada: carboplatino/gemcitabina o carboplatino/paclitaxel o carboplatino/doxorubicina liposomal, más bevacizumab, seguida de bevacizumab como mantenimiento (hasta progresión o toxicidad). 8.2. Para pacientes con CEO de alto grado avanzado o metastásico en recaída, platino-resistentes, se sugiere: Tratamiento secuencial con quimioterapia, preferiblemente con un agente único que no sea un platino (paclitaxel semanal o doxorrubicina liposomal pegilada o docetaxel o etopósido oral o gemcitabina o trabectidina o topotecan). El paclitaxel semanal o la doxorrubicina liposomal pegilada o el topotecan pueden ser administrados con o sin bevacizumab. Existen otros agentes que se consideran potencialmente act ivos (capecitabina, ciclofosfamida, ifosfamida, irinotecán, oxaliplatino, pemetrexed, vinorelbina, ciclofosfamida), que se podrían recomendar para líneas posteriores. Las pacientes con receptores hormonales positivos que no toleran o no tienen respuesta a los regímenes citotóxicos pueden recibir terapia hormonal con tamoxifeno u otros agentes, incluidos los inhibidores de la aromatasa (anastrozol y letrozol) o acetato de leuprolide o acetato de megestrol. Pacientes con PSC ≥ 3 deberían ser consideradas solo para el mejor cuidado de soporte. 8.3. Terapia de mantenimiento con inhibidores PARP. Para pacientes con CEO de alto grado avanzado o metastásico en recaída estadios III/IV BRCA1/2 (positivo, negativo o desconocido), que hayan recibido dos o más líneas de quimioterapia basada en platino y hayan alcanzado RC/RP, se sugiere utilizar olaparib, niraparib o rucaparib. El niraparib podría ser útil en pacientes BRCA 1/2 +/-/desconocido, al igual que el rucaparib, sin embargo, este último no tiene aún aprobación del ente regulador en Colombia. Conclusiones: se espera que las recomendaciones emitidas en este consenso contribuyan a mejorar la atención clínica, el impacto oncológico y la calidad de vida de estas mujeres.