Deciphering the Molecular Mechanisms behind Drug Resistance in Ovarian Cancer to Unlock Efficient Treatment Options.

Ovarian cancer is a highly lethal form of gynecological cancer. This disease often goes undetected until advanced stages, resulting in high morbidity and mortality rates. Unfortunately, many patients experience relapse and succumb to the disease due to the emergence of drug resistance that significantly limits the effectiveness of currently available oncological treatments. Here, we discuss the molecular mechanisms responsible for resistance to carboplatin, paclitaxel, polyadenosine diphosphate ribose polymerase inhibitors, and bevacizumab in ovarian cancer. We present a detailed analysis of the most extensively investigated resistance mechanisms, including drug inactivation, drug target alterations, enhanced drug efflux pumps, increased DNA damage repair capacity, and reduced drug absorption/accumulation. The in-depth understanding of the molecular mechanisms associated with drug resistance is crucial to unveil new biomarkers capable of predicting and monitoring the kinetics during disease progression and discovering new therapeutic targets.

Treatment of Psoriasis Patients with Latent Tuberculosis Using IL-17 and IL-23 Inhibitors: A Retrospective, Multinational, Multicentre Study.

BACKGROUND: Tuberculosis has a major global impact. Immunocompetent hosts usually control this disease, resulting in an asymptomatic latent tuberculosis infection (LTBI). Because TNF inhibitors increase the risk of tuberculosis reactivation, current guidelines recommend tuberculosis screening before starting any biologic drug, and chemoprophylaxis if LTBI is diagnosed. Available evidence from clinical trials and real-world studies suggests that IL-17 and IL-23 inhibitors do not increase the risk of tuberculosis reactivation. OBJECTIVE: To evaluate psoriasis patients with treated or untreated newly diagnosed LTBI who received IL-17 and IL-23 inhibitors and the tolerability/safety of tuberculosis chemoprophylaxis. METHODS: This is a retrospective, observational, multinational study from a series of 14 dermatology centres based in Portugal, Spain, Italy, Greece and Brazil, which included adult patients with moderate-to-severe chronic plaque psoriasis and newly diagnosed LTBI who were treated with IL-23 or IL-17 inhibitors between January 2015 and March 2022. LTBI was diagnosed in the case of tuberculin skin test and/or interferon gamma release assay positivity, according to local guideline, prior to initiating IL-23 or IL-17 inhibitor. Patients with prior diagnosis of LTBI (treated or untreated) or treated active infection were excluded. RESULTS: A total of 405 patients were included; complete/incomplete/no chemoprophylaxis was administered in 62.2, 10.1 and 27.7% of patients, respectively. The main reason for not receiving or interrupting chemoprophylaxis was perceived heightened risk of liver toxicity and hepatotoxicity, respectively. The mean duration of biological treatment was 32.87 ± 20.95 months, and only one case of active tuberculosis infection (ATBI) was observed, after 14 months of treatment with ixekizumab. The proportion of ATBI associated with ixekizumab was 1.64% [95% confidence interval (CI): 0-5.43%] and 0% for all other agents and 0.46% (95% CI 0-1.06%) and 0% for IL-17 and IL-23 inhibitors, respectively (not statistically significant). CONCLUSIONS: The risk of tuberculosis reactivation in patients with psoriasis and LTBI does not seem to increase with IL-17 or IL-23 inhibitors. IL-17 or IL-23 inhibitors should be preferred over TNF antagonists when concerns regarding tuberculosis reactivation exists. In patients with LTBI considered at high risk for developing complications related to chemoprophylaxis, this preventive strategy may be waived before initiating treatment with IL-17 inhibitors and especially IL-23 inhibitors.

Long-term patient-reported outcomes from monarchE: Abemaciclib plus endocrine therapy as adjuvant therapy for HR+, HER2-, node-positive, high-risk, early breast cancer.

BACKGROUND: In monarchE, abemaciclib demonstrated a sustained benefit in invasive disease-free survival and a tolerable safety profile at 42-months median follow-up. With no expected disease-related symptoms, therapies in the adjuvant setting should preserve quality of life (QoL). With all patients off abemaciclib, we report updated patient-reported outcomes (PROs) for the full 2-year treatment period and follow-up. METHODS: Patients completed PROs including FACT-B, FACT-ES, and FACIT-Fatigue at baseline, 3, 6, 12, 18, and 24 months during treatment, and 1, 6, and 12 months after treatment discontinuation. Mixed effects repeated measures model estimated changes from baseline within and between arms for QoL scales and individual items. Meaningful changes were prespecified and no statistical testing was performed. Frequencies of responses to items associated with relevant adverse events and treatment bother were summarized. RESULTS: At baseline, completion rates for PRO instruments were >96 %. Mean changes from baseline for all QoL scales were numerically similar within and between arms (ie, less than prespecified thresholds). The same was observed for all individual items, except diarrhea. Within abemaciclib arm, meaningful differences for diarrhea were observed at 3 and 6 months (mean increases of 1.19 and 1.03 points on 5-point scale, respectively). During treatment, most patients in both arms (69-78 %) reported being bothered "a little bit" or "not at all" by side effects. Overall, patterns for fatigue were similar between arms. During post-treatment follow-up, PROs in both arms were similar to baseline. CONCLUSION: PRO findings confirm a tolerable and reversible toxicity profile for abemaciclib. QoL was preserved with the addition of adjuvant abemaciclib to endocrine therapy, supporting its use in patients with HR+, HER2-, high-risk early breast cancer.

Metastatic Cervical Cancer: A Case That Recalls the Importance of a Multidisciplinary Approach.

Cervical cancer is one of the most common neoplasms in women. Usually, this cancer is only symptomatic in advanced stages and is associated with a poor prognosis. We present the case of a 34-year-old woman with localized cervical cancer at diagnosis treated with surgery in 2011. Six years later, she presented recurrent disease with vaginal, pelvic, and lung metastases. Since then, the patient completed three lines of chemotherapy and a line of immunotherapy, and she was submitted to external radiotherapy and orthopedic surgery. Currently, the patient keeps regular follow-ups and maintains a good performance status. The treatment of recurrent cervical cancer remains a challenge, and the prognosis is poor. This case emphasized the importance of multidisciplinary discussion towards cases of locally advanced or metastatic cervical cancer, which may change this paradigm.

Complicated Cutaneous Leishmaniasis in a Patient under Combined Immunosuppression.

Species associated with visceral leishmaniasis, such as L. infantum, may be responsible for cutaneous leishmaniasis (CL), particularly in the Mediterranean region. In immunosuppressed hosts, classification as complicated CL is essential, as the risk of mucosal leishmaniasis warrants systemic therapy. We report the case of a forty-seven-year-old male living in Portugal, with Fabry disease and receiving immunosuppressive treatment with adalimumab and methotrexate for Crohn's disease. There was no travel history outside of Europe. He presented a two-year-old, 5.5 cm plaque with a well-defined hyperkeratotic elevated border and central, painless ulceration on his back. The biopsy revealed parasites inside macrophages suggestive of Leishmania, and PCR identified the species as L. infantum. A biopsy via nasal endoscopy excluded mucosal involvement. Classification as complicated CL dictated treatment with liposomal amphotericin B and subsequent topical paramomycin. The rarity of CL in Portugal may delay its diagnosis, especially in autochthonous infections. Treatment choice is complicated by the heterogeneity of drugs available worldwide. As the global prevalence of CL increases, it is important to be aware of this diagnosis.

Interval between two-stage exchanges: what is optimal and how do you know?

BACKGROUND: Two-stage exchange arthroplasty remains the most popular option for the treatment of chronic periprosthetic joint infection (PJI). Determining infection eradication and optimal timing of reimplantation can be challenging. Information to allow for a truly informed evidence-based decision is scarce. METHODS: We conducted a critical review of available evidence on the presently available tests to help determine timing of reimplantation. RESULTS: Serology is traditionally used to follow up patients after the first stage. Despite tradition mandates waiting for normal inflammatory markers, there is actually no evidence that they correlate with persistent infection. The role of synovial fluid investigation between stages is also explored. Cultures lack sensitivity and neither differential leukocyte counts nor alternative biomarkers have proven to be accurate in identifying persistent infection with a spacer in situ. We also examined the evidence regarding the optimal time interval between resection and reimplantation and whether there is evidence to support the implementation of a two week "antibiotic holiday" prior to proceeding with reimplantation. Finally, wound healing and other important factors in this setting will be discussed. CONCLUSION: Currently there are no accurate metrics to aid in the decision on the optimal timing for reimplantation. Decision must therefore rely on the resolution of clinical signs and down trending serological and synovial markers.

Quality of Life in Male Breast Cancer: Prospective Study of the International Male Breast Cancer Program (EORTC10085/TBCRC029/BIG2-07/NABCG).

INTRODUCTION: Prospective data about quality of life (QoL) in men with breast cancer (BC) are lacking. A prospective registry (EORTC10085) of men with all BC stages, including a QoL correlative study, was performed as part of the International Male Breast Cancer Program. METHODS: Questionnaires at BC diagnosis included the EORTC QLQ-C30 and BR23 (BC specific module), adapted for men. High functioning and global health/QoL scores indicate high functioning levels/high QoL; high symptom-focused measures scores indicate high symptoms/problems levels. EORTC reference data for healthy men and women with BC were used for comparisons. RESULTS: Of 422 men consenting to participate, 363 were evaluable. Median age was 67 years, and median time between diagnosis and survey was 1.1 months. A total of 114 men (45%) had node-positive early disease, and 28 (8%) had advanced disease. Baseline mean global health status score was 73 (SD: 21), better than in female BC reference data (62, SD: 25). Common symptoms in male BC were fatigue (22, SD: 24), insomnia (21, SD: 28), and pain (16, SD: 23), for which women's mean scores indicated more burdensome symptoms at 33 (SD: 26), 30 (SD: 32), and 29 (SD: 29). Men's mean sexual activity score was 31 (SD: 26), with less sexual activity in older patients or advanced disease. CONCLUSIONS: QoL and symptom burden in male BC patients appears no worse (and possibly better) than that in female patients. Future analyses on impact of treatment on symptoms and QoL over time, may support tailoring of male BC management.

Learning hybrid locomotion skills-Learn to exploit residual actions and modulate model-based gait control.

This work has developed a hybrid framework that combines machine learning and control approaches for legged robots to achieve new capabilities of balancing against external perturbations. The framework embeds a kernel which is a model-based, full parametric closed-loop and analytical controller as the gait pattern generator. On top of that, a neural network with symmetric partial data augmentation learns to automatically adjust the parameters for the gait kernel, and also generate compensatory actions for all joints, thus significantly augmenting the stability under unexpected perturbations. Seven Neural Network policies with different configurations were optimized to validate the effectiveness and the combined use of the modulation of the kernel parameters and the compensation for the arms and legs using residual actions. The results validated that modulating kernel parameters alongside the residual actions have improved the stability significantly. Furthermore, The performance of the proposed framework was evaluated across a set of challenging simulated scenarios, and demonstrated considerable improvements compared to the baseline in recovering from large external forces (up to 118%). Besides, regarding measurement noise and model inaccuracies, the robustness of the proposed framework has been assessed through simulations, which demonstrated the robustness in the presence of these uncertainties. Furthermore, the trained policies were validated across a set of unseen scenarios and showed the generalization to dynamic walking.

Simple and inexpensive synovial fluid biomarkers for the diagnosis of prosthetic joint infection according to the new EBJIS definition.

Introduction: diagnosis of periprosthetic joint infection (PJI) is challenging, as no single test has absolute accuracy. The purpose of this study was to assess the utility of different simple synovial biomarkers in the diagnosis of PJI as defined by the European Bone and Joint Infection Society (EBJIS). Methods: we retrospectively identified all patients undergoing revision hip or knee arthroplasty from 2013 to 2019 on our prospectively maintained database. Only patients with minimum required infection diagnostic workup were included in the study. Patients with comorbidities that may influence the accuracy of synovial biomarkers were excluded. Receiver operator characteristic (ROC) curves were utilised to assess the diagnostic utility of synovial fluid white blood cell (WBC) count, polymorphonuclear leukocyte percentage (PMN %), C-reactive protein (CRP), adenosine deaminase (ADA), and alpha-2-microglobulin (A2M). Results: in total, 102 patients met the inclusion criteria. Of these, 58 were classified as infection unlikely, 8 as infection likely, and 36 as infection confirmed. Synovial WBC count (area under the curve (AUC) 0.94) demonstrated the best utility for the diagnosis of PJI, followed by PMN % (AUC 0.91), synovial CRP (AUC 0.90), ADA (AUC 0.82), and A2M (AUC 0.76). We found added value in the combined interpretation of different biomarkers. We calculated high sensitivity and negative predictive value if at least two of them are negative and high specificity and positive predictive value if at least two are elevated. Conclusion: current results show that synovial fluid investigation is a useful tool for the diagnosis of PJI, and the combined interpretation of simple and inexpensive biomarkers demonstrated improved diagnostic accuracy.

Bone Metastases Detection in Patients with Breast Cancer: Does Bone Scintigraphy Add Information to PET/CT?

BACKGROUND: Positron emission tomography/computed tomography (PET/CT) has become in recent years a tool for breast cancer (BC) staging. However, its accuracy to detect bone metastases is classically considered inferior to bone scintigraphy (BS). The purpose of this work is to compare the effectiveness of bone metastases detection between PET/CT and BS. MATERIALS AND METHODS: Prospective study of 410 female patients treated in a Comprehensive Cancer Center between 2014 and 2020 that performed PET/CT and BS for staging purposes. The image analysis was performed by 2 senior nuclear medicine physicians. The comparison was performed based on accuracy, sensitivity, and specificity on a patient and anatomical region level and was assessed using McNemar's Test. An average ROC was calculated for the anatomical region analysis. RESULTS: PET/CT presented higher values of accuracy and sensitivity (98.0% and 93.83%), surpassing BS (95.61% and 81.48%) in detecting bone disease. There was a significant difference in favor of PET/CT (sensitivity 93.83% vs. 81.48%), however, there is no significant difference in eliminating false positives (specificity 99.09% vs. 99.09%). PET/CT presented the highest accuracy and sensitivity values for most of the bone segments, only surpassed by BS for the cranium. There was a significant difference in favor of PET/CT in the upper limb, spine, thorax (sternum) and lower limb (pelvis and sacrum), and in favor of BS in the cranium. The ROC showed that PET/CT has a higher sensitivity and consistency across the bone segments. CONCLUSION: With the correct imaging protocol, PET/CT does not require BS for patients with BC staging.

Guideline for management of septic arthritis in native joints (SANJO).

This clinical guideline is intended for use by orthopedic surgeons and physicians who care for patients with possible or documented septic arthritis of a native joint (SANJO). It includes evidence and opinion-based recommendations for the diagnosis and management of patients with SANJO.

Patient perspectives on repeated contrast-enhanced mammography and magnetic resonance during neoadjuvant chemotherapy of breast cancer.

BACKGROUND: The burden perceived by the patient of repeated imaging required for neoadjuvant chemotherapy (NAC) monitoring warrants attention due to the increased use of NAC and imaging. PURPOSE: To evaluate and compare the experienced burden associated with repeated contrast-enhanced mammography (CEM) and magnetic resonance imaging (MRI) during NAC for breast cancer from the patient perspective. MATERIAL AND METHODS: Approval from the ethics committee and written informed consent were obtained. In this prospective study, CEM and MRI were performed on 38 patients with breast cancer before, during, and after NAC in a tertiary cancer center. The experienced burden was evaluated with a self-reported questionnaire addressing duration, comfort, anxiety, positioning, and intravenous contrast administration, each measured on a 5-point Likert scale. The participants were asked their preference between CEM or MRI. Statistical comparisons were performed and P<0.05 was considered significant. RESULTS: Most participants (n = 29, 76%) preferred CEM over MRI (P = 0.0008). CEM was associated with a significantly shorter duration (P < 0.001), greater overall comfort (P < 0.01), more comfortable positioning (P = 0.01), and lower anxiety (P = 0.03). Intravenous contrast administration perception revealed no significant difference. Only 4 (10%) participants preferred MRI over CEM, due to the absence of breast compression. CONCLUSION: In the hypothetical scenario of equal diagnostic accuracy, most participants preferred CEM and compared CEM favorably to MRI in all investigated features at repeated imaging required for NAC response assessment. Our results indicate that repeated examinations with CEM is well tolerated and constitutes a patient-friendly alternative for NAC imaging monitoring in breast cancer.

Interpreting Deep Machine Learning Models: An Easy Guide for Oncologists.

Healthcare agents, in particular in the oncology field, are currently collecting vast amounts of diverse patient data. In this context, some decision-support systems, mostly based on deep learning techniques, have already been approved for clinical purposes. Despite all the efforts in introducing artificial intelligence methods in the workflow of clinicians, its lack of interpretability - understand how the methods make decisions - still inhibits their dissemination in clinical practice. The aim of this article is to present an easy guide for oncologists explaining how these methods make decisions and illustrating the strategies to explain them. Theoretical concepts were illustrated based on oncological examples and a literature review of research works was performed from PubMed between January 2014 to September 2020, using "deep learning techniques," "interpretability" and "oncology" as keywords. Overall, more than 60% are related to breast, skin or brain cancers and the majority focused on explaining the importance of tumor characteristics (e.g. dimension, shape) in the predictions. The most used computational methods are multilayer perceptrons and convolutional neural networks. Nevertheless, despite being successfully applied in different cancers scenarios, endowing deep learning techniques with interpretability, while maintaining their performance, continues to be one of the greatest challenges of artificial intelligence.

Bridging the Gap Between Family Medicine and Adolescents: Creating Opportunities Through Sex Education.

INTRODUCTION: Despite school sex education programs defined by law and a national healthcare service with dedicated family planning appointments, the number of teenage pregnancies in Portugal remains significant. The implementation of these programs has been found lacking and a disconnection between adolescents and primary healthcare has been identified. Adolescents have low literacy in contraception, with males being less involved and informed. With this project, the authors sought to propose an alternative approach to school sex education, aiming to improve the global knowledge and adequate use of contraception methods by teenagers.  Material and Methods: Single-arm prospective interventional study was done to assess the impact of a new model of sexual education learning on adolescents' knowledge and use of contraception methods. A 30-minute lecture was developed by Family Medicine residents focusing on the main aspects of contraception and sexual education, using informal language and slideshow presentations. A form using "Yes/No", "True or False", multiple answer, and Likert scale questions was built to assess attitudes and levels of literacy. Two time points were defined to assess the impact of the intervention, applying the form before and one month after the lecture. Four high schools were invited to enter the study, with 190 students enrolled after personal and guardian authorization. IBM SPSS Statistics for Windows, Version 27.0 (Released 2020; IBM Corp., Armonk, New York, United States) was used to perform statistical analysis. RESULTS: A total of 190 participants aged between 14 and 19 years answered both forms. A high 73.7% reported never having had a family planning appointment, with "Not knowing about the possibility" and "Not feeling comfortable with" being the main reasons; 26.3% were sexually active, from which 44% admitted having had intercourse without any kind of protection. Regarding sources of information about contraception, "School," "Internet," and "Friends" were the most prevalent, with only 43% considering the healthcare providers a source. In the contraceptive literacy evaluation, the participants overestimated their knowledge pre-intervention; however, this gap was attenuated in the second evaluation. Moreover, there was a statistically significant improvement in literacy between assessments for all genders. After the intervention, 40.6% reported discussing contraception outside the classroom.  Discussion: The low attendance of the family planning appointments and the low number of participants that considered healthcare services as a source of information in contraception conveys the idea that primary healthcare does not play the desired role in disseminating reliable information on contraception among teenagers. This is concerning considering the overestimated knowledge, low literacy, and risky behaviors identified. The intervention managed to improve the teenagers' literacy while reinforcing the importance of family planning appointments and inciting dialogue among the participants.  Conclusion: This project presents an alternative to current school sex education models and focuses on streamlining communication by resorting to younger communicators, scientific but informal messaging, and short sessions. While extended research comparing against the set models needs to be done, it poses an opportunity to bring adolescents closer to primary healthcare while gathering data to improve clinical practice.

[Intrahospital Protocol for the Management of COVID-19 Disease in Adults]. / Protocolo Intra-Hospitalar para Abordagem da Doença COVID-19 no Adulto.

The COVID-19 pandemic is currently responsible for over 526 million infections and over 6.3 million deaths. As a new disease, the number of papers on the subject is extensive, motivating considerable heterogeneity in its approach. Despite some medicines having sound evidence of benefit, new interventions and strategies continue to be proposed, and some still lack scientific evidence, which hinders a uniform and consensual approach. This article aims to standardize healthcare to adult patients with moderate-to-critical COVID-19, from the emergency department to hospitalization, either in a general ward or in level 2 or level 3 intensive care units, based on the best and most updated scientific evidence available. This protocol presents recommendations for the stratification of adult patients with COVID-19 disease, adequate workup at admission and during hospitalization, inpatient treatment criteria, general treatment measures, pharmacological treatment, management of complications such as organizing pneumonia and bacterial superinfection, thromboprophylaxis, special considerations on pregnancy and breastfeeding and possible future therapies.

A pandemia de COVID-19 é, atualmente, responsável por mais de 526 milhões de infeções e mais de 6,3 milhões de mortes. Como nova doença, é extenso o número de publicações sobre o tema, motivando uma considerável heterogeneidade na sua abordagem. Apesar de existirem terapêuticas com benefício comprovado, continuam a ser propostas novas intervenções e estratégias, algumas das quais carecendo ainda de suporte científico, dificultando assim uma abordagem uniforme e consensual. Este documento tem como objetivo uniformizar, baseando-se na melhor e mais atualizada evidência científica disponível, a prestação de cuidados aos doentes adultos com COVID-19 moderada a crítica, desde o serviço de urgência até à hospitalização, quer em enfermarias gerais, quer em enfermarias de cuidados intensivos de nível 2 e 3. Este protocolo apresenta recomendações para a estratificação da doença COVID-19, critérios de hospitalização, meios complementares de diagnóstico adequados à admissão e durante a hospitalização, medidas terapêuticas gerais e terapêutica farmacológica dirigida, gestão de complicações como pneumonia organizativa e sobreinfeção bacteriana, tromboprofilaxia, considerações especiais na gravidez e amamentação, e possíveis opções terapêuticas futuras.

Prognostic Factors and Survival According to Tumor Subtype in Women With Breast Cancer Brain Metastases.

Breast cancer (BC) is the second most cause of central nervous system (CNS) metastases. Studies report that almost one third of patients (pts) with triple-negative, one-third with human epidermal growth factor receptor 2 (HER2)-positive and 15% of those with hormone receptor-positive, HER2-negative metastatic breast cancer will develop brain metastases. It is known that the development of symptomatic brain metastases in women with advanced breast cancer is associated with poor prognosis, irrespective of local and systemic treatments. In the present study, we aim to determine the association between BC subtypes and CNS metastases occurrence and prognosis. Retrospective analysis of 309 BC patients with CNS metastases, confirmed by pathological and/or radiological methods, treated in a Cancer Center between 2003 and 2021, was obtained to identify clinicopathologic factors associated with early onset of brain metastases and survival outcomes. For analysis purposes, 3 BC subtypes were considered according to hormone receptor status and HER-2 expression: ER and/or PR positive, HER-2 positive and triple negative. The median time between diagnosis of BC and detection of CNS metastases was 43 months, and it was significantly shorter in triple negative group (8 months). Twenty-one patients (6,8%) had CNS metastases at BC diagnosis, with CNS being the first site of recurrence in 35,3%, mainly in HER2 positive. Most of the patients had parenchymal metastases (n = 245) and 37 (12%) had leptomeningeal (LM) disease, with predominance in ER and/or PR positive subtype (70,3%). In patients submitted to CNS surgery, the concordance between primary tumor and metastases subtype was higher in triple negative (76,9%) compared to 63,2% in HER-2 positive and 38,9% in ER and/or PR positive group (P < 0.05). After CNS involvement, 25,4% (n = 34) of patients with triple negative disease did not receive any systemic therapy, compared to 30,6% (n = 41) in HER-2 positive and 44% (n = 59) in ER and/or PR positive groups (P = 0.05). Median survival after CNS metastases was 9 months, but significantly longer in HER-2 positive group (16 months) and in patients submitted to surgical resection of CNS metastases, irrespectively of subtype (22 months vs 5 months in other treatment modalities). In multivariate Cox regression analysis, having HER-2 positive tumor was an independent prognostic factor for increasing survival after CNS metastases (HR 0.60, 95% CI: 0.41-0.87, P = 0.007), regardless the therapeutic strategy. Clinical behavior and prognosis of CNS metastases varies according to BC subtype. The association between LM disease and ER and/or PR positive tumors should be explored in upcoming studies. Also, these patients' prognosis depends on the availability of specific treatment options, therefore, innovative and effective therapeutic approaches are needed, in order to improve survival and quality of life of these patients.

Do Not Forget Poly (Adenosine Diphosphate-Ribose) Polymerase Inhibitors in Ovarian Carcinosarcoma.

Ovarian carcinosarcoma (OCS) is a rare entity with a poor prognosis and without evidence-based therapy. Here, we report the case of a 55-year-old woman with a germline BRCA1 mutation and a stage IV OCS who was proposed olaparib maintenance therapy after three platinum-based chemotherapies in relapsed disease. Currently, the patient has an overall survival of 102 months and progression-free survival of 60 months with olaparib, with a good quality of life and not experiencing any adverse events. Despite the lack of evidence for the use of poly (adenosine diphosphate-ribose) polymerase inhibitors in OCS, our case report proves that patients with a potential biomarker of response to these drugs (such as BRCA mutation and platinum-sensitive disease) derive great benefits from it.

Real-life data on treatment and outcomes in advanced ovarian cancer: An observational, multinational cohort study (RESPONSE trial).

BACKGROUND: This study aimed to describe the treatment strategies and outcomes for women with newly diagnosed advanced high-grade serous or endometrioid ovarian cancer (OC). METHODS: This observational study collected real-world medical record data from eight Western countries on the diagnostic workup, clinical outcomes, and treatment of adult women with newly diagnosed advanced (Stage III-IV) high-grade serous or endometrioid OC. Patients were selected backward in time from April 1, 2018 (the index date), with a target of 120 patients set per country, followed for ≥20 months. RESULTS: Of the 1119 women included, 66.9% had Stage III disease, 11.7% had a deleterious BRCA mutation, and 26.6% received bevacizumab; 40.8% and 39.3% underwent primary debulking surgery (PDS) and interval debulking surgery (IDS), respectively. Of the patients who underwent PDS, 55.5% had no visible residual disease (VRD); 63.9% of the IDS patients had no VRD. According to physician-assessed responses (at the first assessment after diagnosis and treatment), 53.2% of the total population had a complete response and 25.7% had a partial response to first-line chemotherapy after surgery. After ≥20 months of follow-up, 32.9% of the patients were disease-free, 46.4% had progressive disease, and 20.6% had died. Bevacizumab use had a significant positive effect on overall survival (hazard ratio [HR], 0.62; 95% CI, 0.42-0.91; p = .01). A deleterious BRCA status had a significant positive effect on progression-free survival (HR, 0.60; 95% CI, 0.41-0.84; p < .01). CONCLUSIONS: Women with advanced high-grade serous or endometrioid OC have a poor prognosis. Bevacizumab use and a deleterious BRCA status were found to improve survival in this real-world population. LAY SUMMARY: Patients with advanced (Stage III or IV) ovarian cancer (OC) have a poor prognosis. The standard treatment options of surgery and chemotherapy extend life beyond diagnosis for 5 years or more in only approximately 45% of patients. This study was aimed at describing the standard of care in eight Western countries and estimating how many patients who are diagnosed with high-grade serous or endometrioid OC could potentially be eligible for first-line poly(adenosine diphosphate ribose) polymerase inhibitor (PARPi) maintenance therapy. The results highlight the poor prognosis for these patients and suggest that a significant proportion (79%) would potentially be eligible for first-line PARPi maintenance treatment.