The Impact of Liquid Biopsy in Advanced Ovarian Cancer Care.

INTRODUCTION: Ovarian cancer is the third most common gynaecological cancer and has a very high mortality rate. The cornerstone of treatment is complete debulking surgery plus chemotherapy. Even with treatment, 80% of patients have a recurrence. Circulating tumour DNA (ctDNA) has been shown to be useful in the control and follow-up of some tumours. It could be an option to define complete cytoreduction and for the early diagnosis of recurrence. OBJECTIVE: We aimed to demonstrate the usefulness of ctDNA and cell-free DNA (cfDNA) as a marker of complete cytoreduction and during follow-up in patients with advanced ovarian cancer. MATERIAL AND METHODS: We selected 22 women diagnosed with advanced high-grade serous ovarian cancer, of which only 4 had complete records. We detected cfDNA by polymerase chain reaction (PCR), presented as ng/mL, and detected ctDNA with droplet digital PCR (ddPCR). We calculated Pearson correlation coefficients to evaluate correlations among cfDNA, ctDNA, and cancer antigen 125 (CA125), a biomarker. RESULTS: The results obtained in the evaluation of cfDNA and ctDNA and their correlation with tumour markers and the radiology of patients with complete follow-up show disease progression during the disease, stable disease, or signs of recurrence. cfDNA and ctDNA correlated significantly with CA125. Following cfDNA and ctDNA over time indicated a recurrence several months earlier than computed tomography and CA125 changes. CONCLUSION: An analysis of cfDNA and ctDNA offers a non-invasive clinical tool for monitoring the primary tumour to establish a complete cytoreduction and to diagnose recurrence early.

Should We Abandon Intraperitoneal Chemotherapy in the Treatment of Advanced Ovarian Cancer? A Meta-Analysis.

BACKGROUND: Ovarian cancer is the gynaecological malignancy with the highest mortality and diagnosis often occurs in its advanced stages. Standard treatment in these cases is based on complete cytoreductive surgery with adjuvant intravenous chemotherapy. Other types of treatment are being evaluated to improve the prognosis of these patients, including intraperitoneal chemotherapy and antiangiogenic therapy. These may improve survival or time to relapse in addition to intravenous chemotherapy. OBJECTIVE: The aim of this meta-analysis is to determine whether treatment with intravenous chemotherapy remains the gold standard, or whether the addition of intraperitoneal chemotherapy has a benefit in overall survival (OS) and disease-free interval (DFS). MATERIALS AND METHODS: A literature search was carried out in Pubmed and Cochrane, selecting clinical studies and systematic reviews published in the last 10 years. Statistical analysis was performed using the hazard ratio measure in the RevMan tool. RESULTS: Intraperitoneal chemotherapy shows a benefit in OS and DFS compared with standard intravenous chemotherapy. The significant differences in OS (HR: 0.81 CI 95% 0.74-0.88) and in DFS (HR: 0.81 CI 95% 0.75-0.87) are statistically significant (p < 0.00001). There were no clinical differences in toxicity and side-effects. CONCLUSION: Intraperitoneal chemotherapy is an option that improves OS and DFS without significant toxicity regarding the use of intravenous chemotherapy alone. However, prospective studies are needed to determine the optimal dose and treatment regimen that will maintain the benefits while minimising side effects and toxicity and the profile of patients who will benefit most from this treatment.

Analysis of Intraoperative Variables Responsible for the Increase in Lactic Acid in Patients Undergoing Debulking Surgery.

Background: Cytoreductive surgery (CRS) is a complex procedure with a high incidence of perioperative complications. Elevated lactacidaemia levels have been associated with complications and perioperative morbidity and mortality. This study aims to analyse the intraoperative variables of patients undergoing CRS and their relationship with lactacidaemia levels. Methods: This retrospective, observational study included 51 patients with peritoneal carcinomatosis who underwent CRS between 2014 and 2016 at the Abdomino-Pelvic Oncological Surgery Reference Unit (URCOAP) of the General University Hospital of Castellón (HGUCS). The main variable of interest was the level of lactic acid at the end of surgery. Intraoperative variables, including preoperative haemoglobin, duration of surgery, intraoperative bleeding, fluid therapy administered, administration of blood products, and intraoperative peritoneal cancer index (PCI), were analysed. Results: Positive correlations were found between lactic acid levels and PCI, duration of intervention, fluid therapy, intraoperative bleeding, and transfusion of blood products. Additionally, a negative correlation was observed between haemoglobin levels and lactic acid levels. Notably, the strongest correlations were found with operative PCI (ρ = 0.532; p-value < 0.001) and duration of surgery (ρ = 0.518; p-value < 0.001). Conclusions: PCI and duration of surgery are decisive variables in determining the prognosis of patients undergoing debulking surgery. This study suggests that, for each minute of surgery, lactic acid levels increase by 0.005 mmol/L, and for each unit increase in PCI, lactic acid levels increase by 0.060 mmol/L.

Neoadjuvant Chemotherapy plus Interval Cytoreductive Surgery with or without Hyperthermic Intraperitoneal Chemotherapy (NIHIPEC) in the Treatment of Advanced Ovarian Cancer: A Multicentric Propensity Score Study.

INTRODUCTION: Epithelial ovarian cancer (EOC) is primarily confined to the peritoneal cavity. When primary complete surgery is not possible, neoadjuvant chemotherapy (NACT) is provided; however, the peritoneum-plasma barrier hinders the drug effect. The intraperitoneal administration of chemotherapy could eliminate residual microscopic peritoneal tumor cells and increase this effect by hyperthermia. Intraperitoneal hyperthermic chemotherapy (HIPEC) after interval cytoreductive surgery could improve outcomes in terms of disease-free survival (DFS) and overall survival (OS). MATERIALS AND METHODS: A multicenter, retrospective observational study of advanced EOC patients who underwent interval cytoreductive surgery alone (CRSnoH) or interval cytoreductive surgery plus HIPEC (CRSH) was carried out in Spain between 07/2012 and 12/2021. A total of 515 patients were selected. Progression-free survival (PFS) and OS analyses were performed. The series of patients who underwent CRSH or CRSnoH was balanced regarding the risk factors using a statistical analysis technique called propensity score matching. RESULTS: A total of 170 patients were included in each subgroup. The complete surgery rate was similar in both groups (79.4% vs. 84.7%). The median PFS times were 16 and 13 months in the CRSH and CRSnoH groups, respectively (Hazard ratio (HR) 0.74; 95% CI, 0.58-0.94; p = 0.031). The median OS times were 56 and 50 months in the CRSH and CRSnoH groups, respectively (HR, 0.88; 95% CI, 0.64-1.20; p = 0.44). There was no increase in complications in the CRSH group. CONCLUSION: The addition of HIPEC after interval cytoreductive surgery is safe and increases DFS in advanced EOC patients.

Surgery in Recurrent Ovarian Cancer: A Meta-Analysis.

Background: The second cytoreductive surgery performed for a patient who has recurrent ovarian cancer remains controversial. Our study analyzes overall survival (OS) and disease-free survival (DFS) for cytoreductive surgery in addition to chemotherapy in recurrent ovarian cancer instead of chemotherapy alone. Methods: A meta-analysis was conducted using PubMed and the Cochrane database of systematic reviews to select randomized controlled studies. In total, three randomized studies were used, employing a total of 1249 patients. Results: The results of our meta-analysis of these randomized controlled trials identified significant differences in OS (HR = 0.83, IC 95% 0.70-0.99, p < 0.04) and DFS (HR = 0.63, IC 95% 0.55-0.72, p < 0.000001). A subgroup analysis comparing complete cytoreductive surgery and surgery with residual tumor achieved better results for both OS (HR = 0.65, IC 95% 0.49-0.86, p = 0.002) and DFS (HR = 0.67, IC 95% 0.53-0.82, p = 0.0008), with statistical significance. Conclusions: A complete secondary cytoreductive surgery (SCS) in recurrent ovarian cancer (ROC) demonstrates an improvement in the OS and DFS, and this benefit is most evident in cases where complete cytoreductive surgery is achieved. The challenge is the correct patient selection for secondary cytoreductive surgery to improve the results of this approach.

Effectiveness of Hyperthermic Intraperitoneal Chemotherapy Associated with Cytoreductive Surgery in the Treatment of Advanced Ovarian Cancer: Systematic Review and Meta-Analysis.

OBJECTIVE: The use of hyperthermic intraperitoneal chemotherapy (HIPEC) as a treatment for epithelial ovarian cancer remains controversial. Our study aims to analyze the overall survival and disease-free survival for the use of HIPEC as a treatment for advanced epithelial ovarian cancer after neoadjuvant chemotherapy. METHODS: A systematic review and meta-analysis was carried out using PubMed, Cochrane, Web of Science, and ClinicalTrials.gov. A total of six studies were used, comprising a total of 674 patients. RESULTS: The results of our meta-analysis of all studies analyzed together (observational and randomized controlled trials (RCT)) did not achieve significant results. Contrary to the OS (HR = 0.56, 95% IC = 0.33-0.95, p = 0.03) and DFS (HR = 0.61, 95% IC = 0.43-0.86, p < 0.01) of the RCT analyzed separately, a clear impact on survival was suggested. The subgroup analysis showed that studies making use of higher temperatures (≥42 °C) for a shorter period of time (≤60 min) achieved better results for both OS and DFS, as well as the use of cisplatin as the form of chemotherapy in HIPEC. Moreover, the use of HIPEC did not increase high-grade complications. CONCLUSIONS: The addition of HIPEC to cytoreductive surgery demonstrates an improvement in OS and DFS for patients with epithelial ovarian cancer in advanced stages, without an increase in the number of complications. The use of cisplatin as chemotherapy in HIPEC obtained better results.

Fertility-Sparing Surgery versus Radical Hysterectomy in Early Cervical Cancer: A Propensity Score Matching Analysis and Noninferiority Study.

OBJECTIVE: Fertility-sparing surgery (FSS) is the treatment of choice for patients with early cervical cancer (ECC) and fertility desire, but survival rates compared to radical hysterectomy (RH) have been scarcely reported. The aim of this study was to analyse the oncological outcomes of FSS compared to a balanced group of standard RH. METHODS: A retrospective multicentre study of ECC patients who underwent FSS or RH was carried out in 12 tertiary hospitals in Spain between January 2005 and January 2019. The experimental group included patients who underwent a simple and radical trachelectomy, and the control group included patients who underwent RH. Optimal 1:1 propensity score (PS) matching analysis was performed to balance the series. RESULTS: The study included 222 patients with ECC; 111 (50%) were treated with FSS, and 111 (50%) were treated with RH. After PS matching, a total of 38 patients in the FSS group and 38 patients in the RH group were analysed. In both groups, the overall survival (HR 2.5; CI 0.89, 7.41) and recurrence rates (28.9% in the FSS group vs. 13.2% in RH group) were similar. The rate of disease-free survival at 5 years was 68.99% in the FSS group and 88.01% in the RH group (difference of -19.02 percentage points; 95% CI -32.08 to -5.96 for noninferiority). In the univariate analysis, only tumour size reached statistical significance. CONCLUSION: FSS offers excellent disease-free and overall survival in women with ECC with fertility desire and is not inferior compared to RH.

Comparison of Peritoneal Carcinomatosis Scoring Methods in Predicting Resectability and Prognosis in Gynecologic Malignancies.

OBJECTIVE: Peritoneal carcinomatosis is a disease's presentation in the advanced stages of many gynecologic tumours. The distribution and volume of the disease are the main factors in achieving complete debulking. Diagnostic laparoscopy is a technique to allow evaluation of the disease. This study's objective is to compare two laparoscopic scores (Fagotti's index and Sugarbaker's peritoneal cancer index (PCI)) and assess the diagnostic accuracy to select patients for neoadjuvant treatment and reduce unnecessary laparotomies. METHODS: A non-randomised retrospective cohort study was conducted in patients with peritoneal carcinomatosis (ovarian and endometrial origin) who underwent laparoscopy and subsequent laparotomy. We evaluated the scores' ability to predict incomplete surgery and whether they were related to the patients' prognosis. RESULTS: We included 34 patients, of which 23.5% received neoadjuvant chemotherapy. The rate of complete cytoreductive surgery was 79.4% (n = 27 patients). The highest sensitivity was obtained with a PCI value greater than 20. It was the best parameter to determine incomplete debulking. Survival curves were analysed according to the "cut off" established for each score, and statically significant differences were found using PCI with respect to Fagotti's Index. However, these differences were not found with Fagotti's score. CONCLUSION: The best diagnostic method to classify patients with peritoneal cancer is the PCI. It could be adapted to each surgical team because it allows identifying the "cut off point", which depends on incomplete surgery rate.

Validation of three predictive models for suboptimal cytoreductive surgery in advanced ovarian cancer.

The standard treatment for advanced ovarian cancer (AOC) is cytoreduction surgery and adjuvant chemotherapy. Tumor volume after surgery is a major prognostic factor for these patients. The ability to perform complete cytoreduction depends on the extent of disease and the skills of the surgical team. Several predictive models have been proposed to evaluate the possibility of performing complete cytoreductive surgery (CCS). External validation of the prognostic value of three predictive models (Fagotti index and the R3 and R4 models) for predicting suboptimal cytoreductive surgery (SCS) in AOC was performed in this study. The scores of the 3 models were evaluated in one hundred and three consecutive patients diagnosed with AOC treated in a tertiary hospital were evaluated. Clinicopathological features were collected prospectively and analyzed retrospectively. The performance of the three models was evaluated, and calibration and discrimination were analyzed. The calibration of the Fagotti, R3 and R4 models showed odds ratios of obtaining SCSs of 1.5, 2.4 and 2.4, respectively, indicating good calibration. The discrimination of the Fagotti, R3 and R4 models showed an area under the ROC curve of 83%, 70% and 81%, respectively. The negative predictive values of the three models were higher than the positive predictive values for SCS. The three models were able to predict suboptimal cytoreductive surgery for advanced ovarian cancer, but they were more reliable for predicting CCS. The R4 model discriminated better because it includes the laparotomic evaluation of the peritoneal carcinomatosis index.

Postoperative Intestinal Fistula in Primary Advanced Ovarian Cancer Surgery.

BACKGROUND: Advanced ovarian cancer (AOC) requires an aggressive surgery with large visceral resections in order to achieve an optimal or complete cytoreduction and increase the patient's survival. However, the surgical aggressiveness in the treatment of AOC is not exempt from major complications, such as the gastrointestinal fistula (GIF), which stands out among others due to its high morbidity and mortality. METHODS: We evaluated the clinicopathological features in patients with AOC and their association with GI. Data for 107 patients with AOC who underwent primary debulking surgery were analyzed retrospectively. Clinicopathological features, including demographic, surgical procedures and follow-up data, were analyzed in relation to GIF. RESULTS: GIF was present in 11% of patients in the study, 5 (4.5%) and 7 (6.4%) of colorectal and small bowel origin, respectively. GIF was significantly associated with peritoneal cancer index (PCI) >20, more than 2 visceral resections, and multiple digestive resections. Overall and disease-free survival were also associated with GIF. Multivariate analysis identified partial bowel obstruction and operative bleeding as independent prognostic factors for survival. The presence of GIF is positively associated with poor prognosis in patients with AOC. CONCLUSION: Given the importance of successful cytoreductive surgery in AOC, the assessment of the amount of tumor and the aggressiveness of the surgery to avoid the occurrence of GIF become a priority in patients with AOC.

Correction to: Outcome quality standards in advanced ovarian cancer surgery.

An amendment to this paper has been published and can be accessed via the original article.

Outcome quality standards in advanced ovarian cancer surgery.

INTRODUCTION: Advanced ovarian cancer surgery (AOCS) frequently results in serious postoperative complications. Because managing AOCS is difficult, some standards need to be established that allow surgeons to assess the quality of treatment provided and consider what aspects should improve. This study aimed to identify quality indicators (QIs) of clinical relevance and to establish their acceptable quality limits (i.e., standard) in AOCS. MATERIALS AND METHODS: We performed a systematic search on clinical practice guidelines, consensus conferences, and reviews on the outcome and quality of AOCS to identify which QIs have clinical relevance in AOCS. We then searched the literature (from January 2006 to December 2018) for each QI in combination with the keywords of advanced ovarian cancer, surgery, outcome, and oncology. Standards for each QI were determined by statistical process control techniques. The acceptable quality limits for each QI were defined as being within the limits of the 99.8% interval, which indicated a favorable outcome. RESULTS: A total of 38 studies were included. The QIs selected for AOCS were complete removal of the tumor upon visual inspection (complete cytoreductive surgery), a residual tumor of < 1 cm (optimal cytoreductive surgery), a residual tumor of > 1 cm (suboptimal cytoreductive surgery), major morbidity, and 5-year survival. The rates of complete cytoreductive surgery, optimal cytoreductive surgery, suboptimal cytoreductive surgery, morbidity, and 5-year survival had quality limits of < 27%, < 23%, > 39%, > 33%, and < 27%, respectively. CONCLUSION: Our results provide a general view of clinical indicators for AOCS. Acceptable quality limits that can be considered as standards were established.

A Machine Learning Approach to Design an Efficient Selective Screening of Mild Cognitive Impairment.

Mild cognitive impairment (MCI) is the first sign of dementia among elderly populations and its early detection is crucial in our aging societies. Common MCI tests are time-consuming such that indiscriminate massive screening would not be cost-effective. Here, we describe a protocol that uses machine learning techniques to rapidly select candidates for further screening via a question-based MCI test. This minimizes the number of resources required for screening because only patients who are potentially MCI positive are tested further. This methodology was applied in an initial MCI research study that formed the starting point for the design of a selective screening decision tree. The initial study collected many demographic and lifestyle variables as well as details about patient medications. The Short Portable Mental Status Questionnaire (SPMSQ) and the Mini-Mental State Examination (MMSE) were used to detect possible cases of MCI. Finally, we used this method to design an efficient process for classifying individuals at risk of MCI. This work also provides insights into lifestyle-related factors associated with MCI that could be leveraged in the prevention and early detection of MCI among elderly populations.

[Life styles associated cognitive impairment. Study from the community pharmacy]. / Estilos de vida asociados a deterioro cognitivo. Estudio preliminar desde la farmacia comunitaria.

OBJECTIVE: Frequency of cognitive impairment among people over 65 years old in community pharmacy. Study of asssociated factors, referral of cases to the specialist and inclusion in a program of health education. MATERIAL AND METHODS: Cross-sectional study of prevalence, frequency, conducted in four pharmacies (two urban and two rural pharmacies) in the Autonomous Community of Valencia. PARTICIPANTS: people over 65 years old who come to the pharmacy and who agree to participate in the study after signing an informed consent. It is used as the initial screening test, the Short Portable Mental State Questionnaire of Pfeiffer. Pfeiffer positive cases undergo a second test (Mini-Mental State Examination, NORMACODEM version). A questionnaire designed specifically for the study has been used to collect information. It includes questions to gain demographic data, questions on lifestyle and chronic diseases. We used analysis logistic regression multilevel. RESULTS: 245 patients have participated (76% of respondents). 12.65% were detected to have cognitive impairment. In the Logistic regression analysis multivariate there is a relation between cognitive impairment and some variables: age, lack of reading habit, unusual reading habit, sleeping less than 6 or more than 8 hours a day. Only 12.9% wanted to be referred for clinical evaluation and 42% were included in a cognitive training program. CONCLUSIONS: There are asssociation between lifestyle habits that are modifiable and cognitive impairment.