Molecular classification improves preoperative risk assessment of endometrial cancer.

OBJECTIVE: We aimed to evaluate the performance of endometrial cancer (EC) molecular classification in predicting extrauterine disease after primary surgery alone and in combination with other clinical data available in preoperative setting. METHODS: Retrospective single-center observational study including patients with endometrial adenocarcinoma treated with primary surgery between December 1994 and May 2022. Molecular profiling was performed using immunohistochemistry of p53, MLH1, PMS2, MSH2 and MSH6; and KASP genotyping of the 6 most common mutations of POLE gene. Clinical, pathological and imaging information was reviewed. Logistic regression, regression trees and random forest classification techniques (CART) were performed. RESULTS: We enrolled 658 patients, 47 with POLEmut (7.1%), 234 with MMRd (35.6%), 95 with p53abn (14.4%) and 282 with NSMP (42.8%) tumors. Advanced stage after primary surgery (III-IV FIGO 2009) was diagnosed in 11.7% of patients, p53abn tumors showed increased extrauterine spread (34.1%) and nodal involvement (30.1%) (p < .001). In multivariate analysis, only p53abn subgroup (aOR = 16.0, CI95% = 1.5-165.1) and radiological suspicion of extrauterine disease (aOR = 24.2, CI95% = 12.2-48.2) independently predicted the finding of extrauterine disease after primary surgery. In patients with preoperative uterine-confined disease, deep myometrial and cervical involvement in radiological assessment and p53abn molecular subtype were the best variables to identify patients at-risk of occult extrauterine disease after the staging surgery. CONCLUSION: EC molecular classification is more accurate than histotype or grade in preoperative biopsy to predict advanced disease, and together with imaging tests are the most reliable preoperative information. This work provides an initial framework for using molecular information preoperatively to tailor surgical treatment.

Encorafenib and binimetinib followed by radiotherapy for patients with BRAFV600-mutant melanoma and brain metastases (E-BRAIN/GEM1802 phase II study).

BACKGROUND: Encorafenib plus binimetinib (EB) is a standard of care treatment for advanced BRAFV600-mutant melanoma. We assessed efficacy and safety of encorafenib plus binimetinib in patients with BRAFV600-mutant melanoma and brain metastasis (BM) and explored if radiotherapy improves the duration of response. METHODS: E-BRAIN/GEM1802 was a prospective, multicenter, single arm, phase II trial that enrolled patients with melanoma BRAFV600-mutant and BM. Patients received encorafenib 450 mg once daily plus binimetinib 45 mg BID, and those who achieved partial response or stable disease at first tumor assessment were offered radiotherapy. Treatment continued until progression.Primary endpoint was intracranial response rate (icRR) after 2 months of EB, establishing a futility threshold of 60%. RESULTS: The study included 25 patients with no BM symptoms and 23 patients with BM symptoms regardless of using corticosteroids. Among them, 31 patients (64.6%) received sequential radiotherapy. After two months, icRR was 70.8% (95% CI: 55.9-83.1); 10.4% complete response. Median intracranial PFS and OS were 8.5 (95% CI: 6.4-11.8) and 15.9 (95% CI: 10.7-21.4) months, respectively (8.3 months for icPFS and 13.9 months OS for patients receiving RDT). Most common grade 3-4 treatment-related adverse event was alanine aminotransferase (ALT) increased (10.4%). CONCLUSION: Encorafenib plus binimetinib showed promising clinical benefit in terms of icRR, and tolerable safety profile with low frequency of high grade TRAEs, in patients with BRAFV600-mutant melanoma and BM, including those with symptoms and need for steroids. Sequential radiotherapy is feasible but it does not seem to prolong response.

A Phase II Trial of Stereotactic Body Radiation Therapy and Androgen Deprivation for Oligometastases in Prostate Cancer (SBRT-SG 05).

PURPOSE: SBRT-Spanish Group-05 (ClinicalTrials.gov.Identifier: NCT02192788) is a collaborative (SBRT-SG, Grupo de Investigación Clínica en Oncología Radioterápica, and Sociedad Española de Oncología Radioterápica) prospective multicenter phase II trial testing stereotactic body radiation therapy (SBRT) and androgen deprivation therapy (ADT) in patients with oligorecurrent prostate cancer. METHODS AND MATERIALS: Two cohorts of patients with prostate cancer in an oligorecurrent stage (hormone-sensitive in the principal cohort and castration-resistant in the exploratory cohort) were assigned to receive ADT and SBRT for at least 24 months from the time of the enrollment. Concomitant treatment with chemotherapy, abiraterone, or enzalutamide was not allowed. Oncologic outcomes were assessed in both cohorts. Toxicity was prospectively analyzed. RESULTS: From 2014 to 2019, 81 patients with a total of 126 lesions from 14 centers met the inclusion criteria, 14 of whom were castration-resistant. With a median follow-up of 40 months (12-58 months), 3-year local recurrence-free survival was 92.5% (95% CI, 79.9%-96.3%) and 85.7% (95% CI, 48.2%-95.6%) in the principal and exploratory cohorts, respectively. In the principal cohort, biochemical relapse-free survival and metastasis progression-free survival at 1, 2, and 3 years were 91% (95% CI, 81%-95.8%), 73.7% (95% CI, 61.1%-82.8%), 50.6% (95% CI, 36.2%-63.3%), and 92% (95% CI, 83%-97%), 81% (95% CI, 70%-89%), and 67% (95% CI, 53%-77%), respectively. In the exploratory cohort, metastasis progression-free survival at 1, 2, and 3 years was 64% (95% CI, 34%-83%), 43% (95% CI, 18%-66%), and 26% (95% CI, 7%-51%), respectively. None of the patients developed grade III or higher toxicity or symptoms related to local progression, and only 2 (2.4%) patients developed grade II toxicity. CONCLUSIONS: The combination of SBRT and ADT is safe and shows favorable clinical outcomes in patients with hormone-sensitive and castration-resistant prostate cancer. Validation studies are needed in patients with castration-resistant prostate cancer.

Multi-institutional Analysis of Metastasis-directed Therapy with or Without Androgen Deprivation Therapy in Oligometastatic Castration-sensitive Prostate Cancer.

BACKGROUND: Metastasis-directed therapy (MDT) is increasingly being used in oligometastatic castration-sensitive prostate cancer (omCSPC). However, it is currently unclear how to optimally integrate MDT with the standard of care of systemic hormonal therapy. OBJECTIVE: To report long-term outcomes of MDT alone versus MDT and a defined course of androgen deprivation therapy (ADT) in omCSPC. DESIGN, SETTING, AND PARTICIPANTS: Here, a multicenter, international retrospective cohort of omCSPC as defined by conventional imaging was reported. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Biochemical progression-free survival (bPFS), distant progression-free survival (dPFS), and combined biochemical or distant progression-free survival (cPFS) were evaluated with Kaplan-Meier and multivariable Cox proportional hazard regression models. RESULTS AND LIMITATIONS: A total of 263 patients were included, 105 with MDT + ADT and 158 with MDT alone. The majority of patients had metachronous disease (90.5%). Five-year bPFS, dPFS, and cPFS were, respectively, 24%, 41%, and 19% in patients treated with MDT + ADT and 11% (hazard ratio [HR] 0.48, 95% confidence interval [CI] 0.36-0.64), 29% (HR 0.56, 95% CI 0.40-0.78), and 9% (HR 0.50, 95% CI 0.38-0.67) in patients treated with MDT alone. On a multivariable analysis adjusting for pretreatment variables, the use of ADT was associated with improved bPFS (HR 0.43, p < 0.001), dPFS (HR 0.45, p = 0.002), and cPFS (HR 0.44, p < 0.001). CONCLUSIONS: In this large multi-institutional report, the addition of concurrent ADT to MDT appears to improve time to prostate-specific antigen progression and distant recurrence, noting that about 10% patients had durable control with MDT alone. Ongoing phase 3 studies will help further define treatment options for omCSPC. PATIENT SUMMARY: Here, we report a large retrospective review evaluating the outcomes of metastasis-directed therapy with or without a limited course of androgen deprivation for patients with oligometastatic castration-sensitive prostate cancer. This international multi-institutional review demonstrates that the addition of androgen deprivation therapy to metastasis-directed therapy (MDT) improves progression-free survival. While a proportion of patients appear to have long-term disease control with MDT alone, further work in biomarker discovery is required to better identify which patients would be appropriate for de-escalated therapy.

Patterns of First Recurrence and Oncological Outcomes in Locally Advanced Cervical Cancer Patients: Does Surgical Staging Play a Role?

BACKGROUND: We aimed to determine whether surgical aortic staging by minimally invasive paraaortic lymphadenectomy (PALND) affects the pattern of first recurrence and survival in treated locally advanced cervical cancer (LACC) patients when compared to patients staged by imaging (noPALND). METHODS: This study was a multicenter observational retrospective cohort study of patients with LACC treated at tertiary care hospitals throughout Spain. The inclusion criteria were histological diagnosis of squamous carcinoma, adenosquamous carcinoma, and/or adenocarcinoma; FIGO stages IB2, IIA2-IVA (FIGO 2009); and planned treatment with primary chemoradiotherapy between 2000 and 2016. Propensity score matching (PSM) was performed before the analysis. RESULTS: After PSM and sample replacement, 1092 patients were included for analysis (noPALND n = 546, PALND n = 546). Twenty-one percent of patients recurred during follow-up, with the PALND group having almost double the recurrences of the noPALND group (noPALND: 15.0%, PALND: 28.0%, p < 0.001). Nodal (regional) recurrences were more frequently observed in PALND patients (noPALND:2.4%, PALND: 11.2%, p < 0.001). Among those who recurred regionally, 57.1% recurred at the pelvic nodes, 37.1% recurred at the aortic nodes, and 5.7% recurred simultaneously at both the pelvic and aortic nodes. Patients who underwent a staging PALND were more frequently diagnosed with a distant recurrence (noPALND: 7.0%, PALND: 15.6%, p < 0.001). PALND patients presented poorer overall, cancer-specific, and disease-free survival when compared to patients in the noPALND group. CONCLUSION: After treatment, surgically staged patients with LACC recurred more frequently and showed worse survival rates.

Molecular profile in endometrial carcinoma: can we predict the lymph node status? A systematic review and meta-analysis.

PURPOSE: Molecular classification of endometrial cancer (EC) has become a promising information to tailor preoperatively the surgical treatment. We aimed to evaluate the rate of lymph node metastases (LNM) in patients with EC according to molecular profile. METHODS: A systematic review and meta-analysis were performed according to PRISMA guidelines by searching in two major electronic databases (PubMed and Scopus), including original articles reporting lymph node metastases according to the molecular classification of EC as categorized in the ESGO-ESMO-ESP guidelines. RESULTS: Fifteen studies enrolling 3056 patients were included. Pooled prevalence LNM when considering only patients undergoing lymph node assessment was 4% for POLE-mutated (95%CI: 0-12%), 22% for no specific molecular profile (95% CI: 9-39%), 23% for Mismatch repair-deficiency (95%CI: 10-40%) and 31% for p53-abnormal (95%CI: 24-39%). CONCLUSIONS: The presence of LNM seems to be influenced by molecular classification. P53-abnormal group presents the highest rate of nodal involvement, and POLE-mutated the lowest.

Oncological outcomes of intraperitoneal chemotherapy in advanced ovarian cancer: BRCA mutation role.

INTRODUCTION: The knowledge of BRCA status offers a chance to evaluate the role of the intraperitoneal route in patients selected by biomolecular profiles after primary cytoreduction surgery in advanced ovarian cancer. MATERIALS AND METHODS: We performed a retrospective, multicenter study to assess oncological outcomes depending on adjuvant treatment (intraperitoneal [IP] vs intravenous [IV]) and BRCA status (BRCA1/2 mutated vs. BRCA wild type [WT]). The primary endpoint was to determine progression-free survival. The secondary objectives were overall survival and toxicity. RESULTS: A total of 288 women from eight centers were included: 177 in the IP arm and 111 in the IV arm, grouped into four arms according to BRCA1/2 status. Significantly better PFS was observed in BRCA1/2-mutated patients with IP chemotherapy (HR: 0.35; 95% CI, 0.16-0.75, p = 0.007), which was not present in BRCA1/2-mutated patients with IV chemotherapy (HR: 0.65; 95% CI, 0.37-1.12, p = 0.14). Significantly better OS was also observed in IP chemotherapy (HR: 0.17; 95% CI, 0.06-043, p < 0.0001), but was not present in IV chemotherapy in relation with BRCA mutation (HR: 0.52; 95% CI, 0.22-1.27, p = 0.15). For BRCA WT patients, worse survival was observed regardless of the adjuvant route used. The IP route was more toxic compared to the IV route, but toxicity was equivalent at the long-term follow-up. CONCLUSION: This retrospective study suggests that BRCA status can help to offer an individualized, systematic treatment after optimal primary surgery for advanced ovarian cancer, but is limited by the small sample size. Prospective trials are essential to confirm these results.

Adenosine and Cortical Plasticity.

Brain plasticity is the ability of the nervous system to change its structure and functioning in response to experiences. These changes occur mainly at synaptic connections, and this plasticity is named synaptic plasticity. During postnatal development, environmental influences trigger changes in synaptic plasticity that will play a crucial role in the formation and refinement of brain circuits and their functions in adulthood. One of the greatest challenges of present neuroscience is to try to explain how synaptic connections change and cortical maps are formed and modified to generate the most suitable adaptive behavior after different external stimuli. Adenosine is emerging as a key player in these plastic changes at different brain areas. Here, we review the current knowledge of the mechanisms responsible for the induction and duration of synaptic plasticity at different postnatal brain development stages in which adenosine, probably released by astrocytes, directly participates in the induction of long-term synaptic plasticity and in the control of the duration of plasticity windows at different cortical synapses. In addition, we comment on the role of the different adenosine receptors in brain diseases and on the potential therapeutic effects of acting via adenosine receptors.

Procalcitonin and C-reactive protein as early markers of anastomotic leakage in intestinal resections for advanced ovarian cancer (EDMOCS).

INTRODUCTION: Serum levels of procalcitonin and C-reactive protein (CRP) have been used to predict anastomotic leakage after colorectal surgery, but information is scarce in advanced ovarian cancer (AOC) surgery with bowel resection. This study aimed to assess the predictive value of procalcitonin and CRP in detecting anastomotic leakage after AOC surgery with bowel resection. The study also aimed to determine the optimal postoperative reference values and the best day for evaluating these markers. MATERIAL AND METHODS: This prospective, observational and multicentric trial included 92 patients with AOC undergoing debulking surgery with bowel resection between 2017 and 2020 in 10 reference hospitals in Spain. Procalcitonin and CRP levels were measured at baseline and on postoperative days 1-6. Receiver operating characteristic analysis was performed to evaluate the predictive value of procalcitonin and CRP at each postoperative day. Sensitivity, specificity, positive and negative predictive values were calculated. RESULTS: Anastomotic leakage was detected in six patients (6.5%). Procalcitonin and CRP values were consistently higher in patients with anastomotic leakage at all postoperative days. The maximum area under the curve (AUC) for procalcitonin was observed at postoperative day 1 (AUC = 0.823) with a cutoff value of 3.8 ng/mL (83.3% sensitivity, 81.3% specificity). For CRP, the maximum AUC was found at postoperative day 3 (AUC = 0.833) with a cutoff level of 30.5 mg/dL (100% sensitivity, 80.4% specificity). CONCLUSIONS: Procalcitonin and C-reactive protein are potential biomarkers for early detection of anastomotic leakage after ovarian cancer surgery with bowel resection. Further prospective studies with a larger sample size are needed to confirm these findings.

Molecular profile is a strong predictor of the pattern of recurrence in patients with endometrial cancer.

OBJECTIVES: To investigate the pattern of first recurrence of disease in patients with endometrial cancer according to molecular classification, and to assess the independent role of molecular profiling in each type of failure. METHODS: Retrospective single-center study including patients diagnosed with endometrial cancer stage I-IVB (International Federation of Gynecology and Obstetrics 2009) between December 1994 and May 2022, who underwent primary surgical treatment and had a complete molecular profile. First recurrence was classified as isolated or multiple, and as vaginal, pelvic, peritoneal, nodal, and distant according to its location. The log-rank test and univariate and multivariate adjusted Cox regression models were used for comparison between groups. RESULTS: A total of 658 patients were included. Recurrence was observed in 122 patients (18.5%) with a recurrence rate of 12.4% among mismatch-repair deficient tumors, 14.5% among non-specific molecular profile, 2.1% among POLE-mutated, and 53.7% among p53-abnormal tumors. Recurrences were found to be isolated in 80 (65.6%) and multiple in 42 (34.4%) patients, with no differences in molecular subtype (p=0.92). Patients with p53-abnormal tumors had a recurrence mainly as distant (28.4%) and peritoneal (21.1%) disease, while patients with non-specific molecular profile tumors presented predominantly with distant failures (10.3%), and mismatch-repair deficient tumors with locoregional recurrences (9.4%).On multivariate analysis, p53-abnormal molecular profile was the only independent risk factor for peritoneal failure (OR=8.54, 95% CI 2.0 to 36.3). Vaginal recurrence was independently associated with p53-abnormal molecular profile (OR=6.51, 95% CI 1.1 to 37.4) and lymphovascular space invasion. p53-abnormal and non-specific molecular profiles were independent predictors for distant recurrence (OR=3.13, 95% CI 1.1 to 8.7 and OR=2.35, 95% CI 1.1 to 5.0, respectively), along with lymphovascular space invasion and high-grade tumors. Molecular profile was not independently associated with pelvic and nodal recurrences. CONCLUSIONS: Endometrial cancer featured different patterns of recurrence depending on the molecular profile. p53-abnormal molecular profiling was the only independent risk factor for peritoneal relapse, while non-specific molecular profile showed a strong association with distant failures.

Challenges and prospects of yeast-based microbial oil production within a biorefinery concept.

Biodiesel, unlike to its fossil-based homologue (diesel), is renewable. Its use contributes to greater sustainability in the energy sector, mainly by reducing greenhouse gas emissions. Current biodiesel production relies on plant- and animal-related feedstocks, resulting in high final costs to the prices of those raw materials. In addition, the production of those materials competes for arable land and has provoked a heated debate involving their use food vs. fuel. As an alternative, single-cell oils (SCOs) obtained from oleaginous microorganisms are attractive sources as a biofuel precursor due to their high lipid content, and composition similar to vegetable oils and animal fats. To make SCOs competitive from an economic point of view, the use of readily available low-cost substrates becomes essential. This work reviews the most recent advances in microbial oil production from non-synthetic sugar-rich media, particularly sugars from lignocellulosic wastes, highlighting the main challenges and prospects for deploying this technology fully in the framework of a Biorefinery concept.

Endometrial cancer PDX-derived organoids (PDXOs) and PDXs with FGFR2c isoform expression are sensitive to FGFR inhibition.

Endometrial cancer (EC) patients with metastatic/recurrent disease have limited treatment options and poor survival outcomes. Recently, we discovered the FGFR2c splice isoform is associated with poor prognosis in EC patients. Here we report the establishment of 16 EC patient-derived xenografts (PDX)-derived organoids (PDXOs) with or without FGFR2c expression. In vitro treatment of 5 EC PDXOs with BGJ398 showed significant cell death in 3 models with FGFR2c expression. PDXs with high/moderate FGFR2c expression showed significant tumour growth inhibition (TGI) following 21-day treatment with FGFR inhibitors (BGJ398 or pemigatinib) and significantly prolonged survival in 4/5 models. Pemigatinib + cisplatin combination therapy (n = 5) resulted in significant TGI and prolonged survival in one of two p53abn PDXs. All five models treated with cisplatin alone showed de novo resistance and no survival benefit. Seven-day treatment with BGJ398 revealed a significant reduction in angiogenesis and CD206 + M2 macrophages. These data collectively support the evaluation of FGFR inhibitors in a clinical trial.

Can the microcystic, elongated and fragmented pattern of invasion influence the evaluation of the depth of myometrial invasion in low-grade endometrioid endometrial cancer using imaging techniques?

Objectives: The microcystic, elongated and fragmented pattern of invasion can be associated with an underestimation of the depth of myometrial invasion by imaging techniques. We aimed to evaluate the influence of microcystic, elongated and fragmented pattern of invasion in the diagnostic performance of transvaginal ultrasound scan and magnetic resonance imaging for the prediction of the depth of myometrial invasion in low-grade endometrioid endometrial carcinomas. Methods: Prospective and consecutive study including all low-grade (G1-G2) endometrioid endometrial carcinomas diagnosed between October 2013 and July 2018 in a tertiary hospital. Preoperative staging was performed with transvaginal ultrasound scan and/or magnetic resonance imaging followed by surgical staging. Final histology was considered as the reference standard. Sensitivity, specificity and diagnostic accuracy for the prediction of depth of myometrial invasion was calculated for both imaging techniques. The STARD 2015 guidelines were used. Results: A total of 136 patients were consecutively included. Transvaginal ultrasound scan was performed in 132 patients and magnetic resonance imaging in 119 patients. The diagnostic accuracy of transvaginal ultrasound scan for the prediction of depth of myometrial invasion in the microcystic, elongated and fragmented negative group (82% (95% confidence interval = 73-88)) was higher compared to the microcystic, elongated and fragmented positive group (61% (95% confidence interval = 36-83)). The diagnostic accuracy of magnetic resonance imaging was also higher in the microcystic, elongated and fragmented negative group (80% (95% confidence interval = 71-87)) compared to the microcystic, elongated and fragmented positive (47% (95% confidence interval = 21-73)). Conclusions: In low-grade endometrioid endometrial carcinomas with a positive microcystic, elongated and fragmented pattern of invasion, the evaluation of the depth of myometrial invasion using transvaginal ultrasound scan and magnetic resonance imaging may be underestimated.

PEACE V-Salvage Treatment of OligoRecurrent nodal prostate cancer Metastases (STORM): Acute Toxicity of a Randomized Phase 2 Trial.

BACKGROUND: Treatment recommendations for patients with limited nodal recurrences are lacking, and different locoregional treatment approaches are currently being used. OBJECTIVE: The aim of this trial is to compare metastasis-directed therapy (MDT) with or without elective nodal pelvic radiotherapy (ENRT). DESIGN, SETTING, AND PARTICIPANTS: PEACE V-Salvage Treatment of OligoRecurrent nodal prostate cancer Metastases (STORM) is an international, phase 2, open-label, randomized, superiority trial (ClinicalTrials.gov identifier: NCT03569241). Patients diagnosed with positron emission tomography-detected pelvic nodal oligorecurrence (five or fewer nodes) following radical local treatment for prostate cancer were randomized in a 1:1 ratio between arm A (MDT and 6 mo of androgen deprivation therapy [ADT]) and arm B (ENRT [25 × 1.8 Gy] with MDT and 6 mo of ADT). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We report the secondary endpoint acute toxicity, defined as worst grade ≥2 Common Terminology Criteria for Adverse Events v4.0 gastrointestinal (GI) or genitourinary (GU) toxicity within 3 mo of treatment. The chi-square test was used to compare toxicity between treatment arms. We also compare the quality of life (QoL) using the European Organisation for Research and Treatment of Cancer QLQ C30 and PR25 questionnaires. RESULTS AND LIMITATIONS: Between June 2018 and April 2021, 196 patients were assigned randomly to MDT or ENRT. Ninety-seven of 99 patients allocated to MDT and 93 of 97 allocated to ENRT received per-protocol treatment. Worst acute GI toxicity proportions were as follows: grade ≥2 events in three (3%) in the MDT group versus four (4%) in the ENRT group (p = 0.11). Worst acute GU toxicity proportions were as follows: grade ≥2 events in eight (8%) in the MDT group versus 12 (13%) in the ENRT group (p = 0.95). We observed no significant difference between the study groups in the proportion of patients with a clinically significant QoL reduction from baseline for any subdomain score area. CONCLUSIONS: No clinically meaningful differences were observed in worst grade ≥2 acute GI or GU toxicity or in QoL subdomains between MDT and ENRT. PATIENT SUMMARY: We found no evidence of differential acute bowel or urinary side effects using metastasis-directed therapy and elective nodal radiotherapy for the treatment of patients with a pelvic lymph node recurrence.

Manejo perioperatorio de medicación anticoagulante y antiagregante antiplaquetaria en radiología intervencionista / Perioperative management of anticoagulants and antiplatelets agents in interventional radiology

Resumen El número de personas en tratamiento con fármacos anticoagulantes o antiplaquetarios está en crecimiento constante debido al aumento de la supervivencia de los pacientes con fibrilación auricular, válvulas cardiacas mecánicas o que han sufrido un evento isquémico o trombótico agudo. Cuando estos pacientes necesitan un procedimiento radiológico intervencionista que acarrea riesgo de sangrado, es necesario analizar el riesgo trombótico del paciente al interrumpir la medicación frente al riesgo hemorrágico del procedimiento para tomar la decisión más adecuada en cada caso. Por tanto, es una decisión individualizada y supone un desafío para los/as radiólogos/as que realicen estas técnicas. Nuestro objetivo en esta revisión es mostrar las recomendaciones actuales sobre el manejo perioperatorio de la medicación anticoagulante y antiplaquetaria, adaptada al intervencionismo radiológico.

Abstract The number of people treated with anticoagulant or antiplatelet agents is constantly growing due to the increased survival of patients with atrial fibrillation, mechanical cardiac valves or who have suffered an acute thrombotic or ischemic event. When these patients need an interventional radiological procedure that carries a risk of bleeding, it is necessary to analyze the thrombotic risk of the patient when interrupting the medication against the hemorrhagic risk of the procedure, to make the most appropriate decision in each case. Therefore, it is an individualized decision, and it is a challenge for radiologists who perform these techniques. Our goal in this review is to update the current recommendations on the perioperative management of anticoagulant and antiplatelet agents, adapted to the radiological interventionism.

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.

Endometrial adenocarcinoma recurring in the lung: impact of molecular profile and role of local therapies on prognosis.

OBJECTIVES: The objective of our study was to describe the characteristics of patients with endometrial cancer diagnosed with a first recurrence involving the lung, and to describe the prognostic role of the molecular profile. We also aimed to describe the prognostic outcomes after local treatment of recurrence (resection of lung metastases or stereotactic body radiation therapy) in a group of patients with isolated lung recurrence. METHODS: This was a retrospective, single-center study between June 1995 and July 2021. The study included patients diagnosed with a first recurrence of endometrial cancer involving the lung. We defined two groups of patients: patients with isolated lung recurrence (confined to the lung) and patients with multisystemic recurrence (in the lung and other locations). RESULTS: Among 1413 patients diagnosed with endometrial cancer in stage IA to IVA of the International Federation of Gynecology and Obstetrics (FIGO) 2009, 64 (4.5%) patients had a first recurrence involving the lung. Of these, 15 (39.1%) were of a non-specific molecular profile, 16 (25%) were p53-abnormal, 15 (23.4%) were mismatch-repair deficient, and 0% POLE-mutated. P53-abnormal patients had the shortest 3 year progression-free survival after recurrence and those with mismatch-repair deficient had the longest 3 year progression-free survival (14.3% (range; 1.6-40.3) and 47.6% (range; 9.1-79.5) respectively, p=0.001). We found no differences on overall survival after recurrence by molecular profile. Thirty-one of 64 (48.4%) patients had an isolated recurrence in the lung, and 16 (25%) patients received local treatment. When comparing patients with isolated lung recurrence, locally treated patients had a longer median progression-free survival than patients treated systemically (41.9 (range, 15.4-NA) vs 7.8 (range, 7.2-10.6) months respectively, p=0.029), a complete response rate of 80% for stereotactic body radiation therapy and a complete resection of 90.9% for surgery. CONCLUSION: Although few patients will benefit from local treatment (stereotactic body radiation therapy or resection) after a recurrence involving the lung, local therapies might be considered as an option in oligometastatic lung recurrences as they achieve high local control rates and better oncological outcomes than systemic treatment alone.

Node Oligorecurrence in Prostate Cancer: A Challenge.

Within the oligometastatic state, oligorecurrent lymph node disease in prostate cancer represents an interesting clinical entity characterized by a relatively indolent biology that makes it unique: it can be treated radically, and its treatment is usually associated with a long period of control and excellent survival. Additionally, it is an emergent situation that we are facing more frequently mainly due to (a) the incorporation into clinical practice of the PSMA-PET that provides strikingly increased superior images in comparison to conventional imaging, with higher sensitivity and specificity; (b) the higher detection rates of bone and node disease with extremely low levels of PSA; and (c) the availability of high-precision technology in radiotherapy treatments with the incorporation of stereotaxic body radiotherapy (SBRT) or stereotaxic ablative radiotherapy (SABR) technology that allows the safe administration of high doses of radiation in a very limited number of fractions with low toxicity and excellent tolerance. This approach of new image-guided patient management is compelling for doctors and patients since it can potentially contribute to improving the clinical outcome. In this work, we discuss the available evidence, areas of debate, and potential future directions concerning the utilization of new imaging-guided SBRT for the treatment of nodal recurrence in prostate cancer.

Accuracy and Survival Outcomes after National Implementation of Sentinel Lymph Node Biopsy in Early Stage Endometrial Cancer.

BACKGROUND: Sentinel lymph node (SLN) biopsy has recently been accepted to evaluate nodal status in endometrial cancer at early stage, which is key to tailoring adjuvant treatments. Our aim was to evaluate the national implementation of SLN biopsy in terms of accuracy to detect nodal disease in a clinical setting and oncologic outcomes according to the volume of nodal disease. PATIENTS AND METHODS: A total of 29 Spanish centers participated in this retrospective, multicenter registry including patients with endometrial adenocarcinoma at preoperative early stage who had undergone SLN biopsy between 2015 and 2021. Each center collected data regarding demographic, clinical, histologic, therapeutic, and survival characteristics. RESULTS: A total of 892 patients were enrolled. After the surgery, 12.9% were suprastaged to FIGO 2009 stages III-IV and 108 patients (12.1%) had nodal involvement: 54.6% macrometastasis, 22.2% micrometastases, and 23.1% isolated tumor cells (ITC). Sensitivity of SLN biopsy was 93.7% and false negative rate was 6.2%. After a median follow up of 1.81 years, overall surivial and disease-free survival were significantly lower in patients who had macrometastases when compared with patients with negative nodes, micrometastases or ITC. CONCLUSIONS: In our nationwide cohort we obtained high sensitivity of SLN biopsy to detect nodal disease. The oncologic outcomes of patients with negative nodes and low-volume disease were similar after tailoring adjuvant treatments. In total, 22% of patients with macrometastasis and 50% of patients with micrometastasis were at low risk of nodal metastasis according to their preoperative risk factors, revealing the importance of SLN biopsy in the surgical management of patients with early stage EC.