Context Of Oncology Research Articles

Communications Is Time for Care: An Italian Monocentric Survey on Human Papillomavirus (HPV) Risk Information as Part of Cervical Cancer Screening.

Human papilloma virus (HPV) infection could be considered a social disease, both for its high incidence, especially in younger subjects, and for the risk of neoplastic evolution linked to viral infection. Therefore, the National Health System, in collaboration with the state, must help women to understand the oncological risk of HPV and suitable methods of prevention. We conducted an Italian monocentric survey on HPV risk information as part of cervical cancer screening. An anonymous questionnaire was administered to 200 women with high-risk positive HPV and low-grade cervical lesions during second-level cervical cancer screening at the Gynecology and Obstetrics Unit of the “San Paolo” Hospital. From this survey, the need to improve communication for patients has emerged, as currently it is not exhaustive. In response to this need, organizational changes have been implemented to centralize the moment of counseling in the second levels of screening and to improve the training of health workers in level I as well as family doctors. In addition, psychological support was also proposed to patients who requested it, as was the dissemination of material such as that produced by GISCI (Italian Cervico-Carcinoma Screening Group) and updated in May 2018, which provides 100 answers to questions on HPV in order to achieve effective and comprehensive communication. This investigation requires further development, and the expansion of this investigation to the multicenter level is already underway. Therefore, this survey will represent a cornerstone for further discussion on the topic considering the necessity of appropriate communication in the oncological context.

Comprehensive immunohistochemical analysis of N6-methyladenosine (m6A) writers, erasers, and readers in endometrial cancer

PurposeN6-methyladenosine (m6A) is the most frequent type of messenger RNA (mRNA) modification and is implicated in diverse physiological processes. The procedure of m6A RNA modification is regulated by a dynamic interaction of writers (METTL3, METTL4, METTL14, WTAP, KIAA1429), erasers (FTO, ALKBH5), and readers (HNRNPA2B1, HNRNPC, YTHDC1, YTHDC1, YTHDF1-3). In the oncological context, alterations in m6A were identified to be critically involved in tumorigenesis, proliferation, angiogenesis, and drug resistance across diverse cancer entities including endometrial cancer (EC).MethodsIn this study, we comprehensively examined the protein expression of m6A writers, readers and erasers by immunohistochemical staining in a cohort of N = 65 EC patients. Protein expression data were analyzed with regard to clinical outcomes.ResultsWe identified enhanced protein expression levels of METTL3, METTL14, FTO, HNRNPA2B1, and HNRNPC, respectively to be of prognostic value and linked to a shortened overall survival in EC.ConclusionOverall, our study points toward dysregulated m6A modification in EC and its possibility to serve as a promising prognostic biomarker.

Untangling the gender pay gap in radiation oncology.

Untangling the gender pay gap in radiation oncology.

How to support parenting in patients with cancer and co-parents? From research to practice.

When a parent is diagnosed with cancer, the entire family is impacted. Patients with cancer and co-parents may no longer feel able to fulfill their parenting roles. The aims of this article are to describe interventions designed to support parenting in the oncological context and to make suggestions for the development and assessment of such interventions. Ten parenting support interventions published in the last 10 years in oncology were identified, among which four randomized controlled trials (RCTs). The therapeutic aims, techniques, and modalities of these interventions were heterogeneous. Five main therapeutic aims were addressed to: increase parents' knowledge, promote parents' emotion regulation, enhance parents' self-efficacy related to parenting, promote parents' support of their children's reactions and coping strategies, and promote open and appropriate parent-child communication. Few studies have combined informational resources with experiential techniques. Very few studies examining the efficacy of parenting support interventions have been published. There is still a need to develop, test, and compare interventions that meet the many needs of parents and their children. Suggestions are made about the contents and formats of parenting support interventions in oncology.

The importance of the urologist in male oncology fertility preservation.

To demonstrate that surgical sperm retrieval (SSR) and spermatogonial stem cell retrieval (SSCR) in an oncological context are safe and successful. This a retrospective study in a tertiary hospital in the UK. Patients requiring fertility preservation from December 2017 to January 2020 were included. Data were analysed with Microsoft Excel 2016 and the Statistical Package for the Social Sciences (version 20). Among 1264 patients referred to the Reproductive Medical Unit at the University College of London Hospitals for cryopreservation prior to gonadotoxic treatment, 39 chose to go forward with SSR/SSCR because they presented as azoo-/cryptozoospermic or an inability to masturbate/ejaculate. Interventions were testicular sperm extraction (23 patients) or aspiration (one), electroejaculation (one), and testicular wedge biopsy for SSCR (14). The median (range) age was 15.0 (10-65) years and the median testosterone level was 4.4 nmoL/L. Primary diagnoses were sarcoma in 11 patients, leukaemia in nine, lymphoma in eight, testicular tumour in five, other oncological haematological entities in two, other solid cancers in two, while two patients had non-oncological haematological diseases. SSR/SSCR could be offered within 7.5 days on average. Chemotherapy could follow within 2 days from SSR/SSCR, and bone marrow transplant occurred within 19.5 days (all expressed as medians). The success rate for SSR was 68.0% (at least one vial/straw collected). The mean (SD) Johnsen score of testicular biopsies was 5.23 (2.25) with a trend towards positive correlation with SSR success (P = 0.07). However, age, hormonal profile and type of cancer did not predict SSR outcome. We show that SSR and SSCR in an oncological context are valid treatment options with a high success rate for patients in which sperm cryopreservation from semen is impossible. By providing an effective pathway, fertility preservation is possible with minimal delay to oncological treatment.

Study on Effective Communication Skills for Good Cancer Care

Even though communication is a key clinical skill in oncology, few physicians and cancer nurses have conventional formal training in this area. Inadequate communications may be upsetting for a patient or family since they frequently need much more information than is often delivered. Many clients leave consultations with questions regarding their diagnosis and prognosis, the value of more tests, and whether or not they are necessary for the management framework or the therapy's underlying therapeutic purpose. Furthermore, communication issues may prevent patients from enrolling in clinical trials, resulting in the delay of useful new treatments in clinics. Inadequate communication between experts or departments may lead to misunderstandings and a loss of trust among team members. Lack of communication and management skills training, according to oncologists, is a big role in their stress, work satisfaction, and emotional tiredness. As a result, many efforts aiming at strengthening cancer healthcare personnel's fundamental effective communication have been launched in recent years. Some of the problems that affect communications in an oncology context, and hence patient care, are discussed in this study. The fundamental conclusion of this research is that communication is beneficial in the treatment of any condition. In this paper, the author provides a comprehensive study on effective communication skills for good cancer care. Further research on the effectiveness of the Contraction Stress Test (CST) in improving healthcare professional communication should focus on improving patient outcomes rather than healthcare workers' views of their abilities.

Tumour cell-activated platelets modulate the immunological activity of CD4+, CD8+, and NK cells, which is efficiently antagonized by heparin

Platelets, key players in haemostasis, are progressively investigated with respect to their role in immunity and inflammation. Although the platelet support to haematogenous cancer cell metastasis has been the subject of multiple studies, their impact on anti-cancer immunity remains unaddressed. Here, we investigated the immunomodulatory potential of platelets upon their activation by MDA-MB-231 breast cancer cells in various in vitro approaches. We provide evidence that platelets as well as their tumour cell-induced releasates increased the ratio of regulatory T cells, shaping an immunosuppressive phenotype in isolated CD4+ cultures. The influence on CD8+ T cells was assessed by detecting the expression of activation markers CD25/CD69 and release of cytolytic and pro-inflammatory proteins. Notably, the platelet preparations differentially influenced CD8+ T cell activation, while platelets were found to inhibit the activation of CD8+ T cells, platelet releasates, in contrast, supported their activation. Furthermore, the NK cell cytolytic activity was attenuated by platelet releasates. Low molecular weight heparin (LMWH), the guideline-based anticoagulant for cancer-associated thrombotic events, is known to interfere with tumour cell-induced platelet activation. Thus, we aimed to investigate whether, unfractionated heparin, LMWH or novel synthetic heparin mimetics can also reverse the immunosuppressive platelet effects. The releasate-mediated alteration in immune cell activity was efficiently abrogated by heparin, while the synthetic heparin mimetics partly outperformed the commercial heparin derivatives. This is the first report on the effects of heparin on rebalancing immunosuppression in an oncological context emerging as a novel aspect in heparin anti-tumour activities.

Advance Directives in Oncology and Haematology: A Long Way to Go—A Narrative Review

Patients living with cancer often experience serious adverse events due to their condition or its treatments. Those events may lead to a critical care unit admission or even result in death. One of the most important but challenging parts of care is to build a care plan according to the patient’s wishes, meeting their goals and values. Advance directives (ADs) allow everyone to give their preferences in advance regarding life sustaining treatments, continuation, and withdrawal or withholding of treatments in case one is not able to speak their mind anymore. While the absence of ADs is associated with a greater probability of receiving unwanted intensive care around the end of their life, their existence correlates with the respect of the patient’s desires and their greater satisfaction. Although progress has been made to promote ADs’ completion, they are still scarcely used among cancer patients in many countries. Several limitations to their acceptance and use can be detected. Efforts should be made to provide tailored solutions for the identified hindrances. This narrative review aims to depict the situation of ADs in the oncology context, and to highlight the future areas of improvement.

The modulatory role of internet-supported mindfulness-based cognitive therapy on extracellular vesicles and psychological distress in people who have had cancer: a protocol for a two-armed randomized controlled study

BackgroundMindfulness-based interventions (MBIs) have been used in oncology contexts as a promising tool with numerous benefits for various health-related and psychosocial outcomes. Despite the increasing popularity of MBIs, few randomized controlled trials (RCTs) have examined their effects upon biological parameters. Specifically, no previous study has examined the effects of MBIs on extracellular vesicles (EVs), which are potentially important markers of health, disease, and stress. Moreover, the lack of RCTs is even more limited within the context of technology-mediated MBIs and long-term effects.MethodsThe current study protocol presents a two-arm, parallel, randomized controlled study investigating the effects of internet-supported mindfulness-based cognitive therapy (MBCT) compared with treatment as usual (TAU). Primary outcomes are psychological distress and EV cargo of distressed participants with previous breast, colorectal, or prostate cancer diagnoses. Secondary outcomes are self-reported psychosocial and health-related measures, and additional biological markers. Outcomes will be assessed at baseline, 4 weeks after baseline (mid-point of the intervention), 8 weeks after baseline (immediately post-intervention), 24 weeks after baseline (after booster sessions), and 52 weeks after baseline. Our goal is to recruit at least 111 participants who have been diagnosed with breast, prostate, or colorectal cancer (cancer stage I to III), are between 18 and 65 years old, and have had primary cancer treatments completed between 3 months and 5 years ago. Half of the participants will be randomized to the TAU group, and the other half will participate in an 8-week online MBCT intervention with weekly group sessions via videoconference. The intervention also includes asynchronous homework, an online retreat after the fifth week, and 4 monthly booster sessions after completion of the 8-week programme.DiscussionThis study will allow characterizing the effects of internet-based MBCT on psychosocial and biological indicators in the context of cancer. The effects on circulating EVs will also be investigated, as a possible neurobiological pathway underlying mind-body intervention effects.Trial registrationClinicalTrials.govNCT04727593 (date of registration: 27 January 2021; date of record verification: 6 October 2021).

Integrative medicine: scientific literature in 2021

To illustrate the novelties in integrative and complementary medicine in 2021, the authors present a selection of six articles. One of them is specifically related to COVID-19. The other articles deal with themes that are always relevant and where complementary approaches represent a real added value. Two articles focus on low back pain, a common problem in primary care medicine. The others examine acupuncture in the oncological context, the use of therapeutic suggestions in an operative context, and Tai Chi. The authors thus provide an overview of the range of possible complementary therapeutic approaches that are increasingly supported by evidence, inviting them to be better integrated into clinical practice.

Review on the Use of Modulated Electro-Hyperthermia as a Stand-Alone Therapy in a Palliative Setting: Potential for Further Research?

Background: Hyperthermia (HT) in oncology was originally applied as a stand-alone treatment (monotherapy), but achieving temperatures required to cause cellular destruction (>43ºC) proved to be challenging. Lower temperatures may increase the risk of dissemination of the treated tumours. Hyperthermia in the current context of oncology therefore aims to achieve moderate temperatures of 39ºC - 41.5ºC and is applied in combination with chemotherapy (ChT) and/or radiotherapy (RT). Modulated electro-hyperthermia (mEHT) applies amplitude modulation to an electric field generated by a capacitive coupled set-up, to selectively heat tumours. As mEHT does not appear to increase the risk of disease dissemination, it has been investigated as a stand-alone treatment for patients with advanced disease and who have exhausted all other treatment options. This report is a descriptive review of papers in oncology which report on the use of mEHT as a stand-alone treatment in a palliative setting. We aim to establish whether there is motivation for the development of trials to further investigate mEHT as a monotherapy in a palliative setting. Methods: A literature search was conducted using the key words “Oncothermia”, “modulated electro-hyperthermia” and “monotherapy”, and case reports were excluded. Only studies which applied mEHT without ChT or RT; for palliative intent; when conventional therapies have failed; or when no further options are available, were included. Results: Six phase I/II studies on tumours of the liver, brain, pancreas, and stomach were included. The studies demonstrated the safety of mEHT; disease stabilisation; and improved quality of life. Conclusion: mEHT may have a role in the palliative management of certain tumours in the absence of any other treatment options. The development of robustly designed studies on mEHT for palliative management of oncology patients is motivated.

Implementation Science to Improve Tobacco Cessation Services in Oncology Care.

Every patient with cancer deserves access to evidence-based tobacco cessation interventions as part of their routine oncology care. The NCI Cancer Moonshot funded the Cancer Center Cessation Initiative (C3I) to help establish and/or expand tobacco treatment programs at 52 NCI-designated Cancer Centers. Although this initiative has broadened the availability of tobacco treatment services across US cancer centers, the reach and utilization of these services remains low among patients. To help address the remaining gap between the availability and utilization of evidence-based treatments for tobacco use in the oncologic context, staff and investigators at C3I sites and the C3I Coordinating Center formed the C3I Implementation Science Working Group. The mission of this working group is to bring together clinicians, scientists, and policymakers who share a common interest in implementation science and treating tobacco use in the oncologic context to collaborate on projects aimed at shrinking the practice gap in this area. Through case study examples, we describe how the C3I Implementation Science Working Group is supporting efforts to identify effective ways to increase the utilization of evidence-based tobacco treatments within cancer treatment settings and promote the broader impact and long-term sustainability of C3I.

Consommations de tabac et d’alcool chez des femmes traitées pour un cancer du sein dans un service de chirurgie oncologique : des comportements fréquents à considérer

Tobacco and alcohol represent the two most important risk factors increasing cancer incidence and mortality, particularly among women with breast cancer. However, few researches have focused on the consumption of psychoactive substances in women treated for breast cancer. The present study describes the prevalence of tobacco and alcohol consumption and their relationships with the sociodemographic, medical and psychological variables in a population of women receiving surgery treatment for breast cancer. Between October 2014 and August 2015, a group of women receiving breast cancer treatment were recruited to participate to a screening and brief intervention program (SBI) for the consumption of tobacco and alcohol, adapted to the oncology context. Data on tobacco and alcohol consumption were collected using two questionnaires: the smoking status identification (NIDA) and alcohol consumption (AUDIT-C). A questionnaire for socio- demographic data and two for psychological data (Thermometer of psychological distress; ESAS), have been used. The medical data were reported by participants and verified on medical records. In a total of 11 months, 120 women with breast cancer were included in this study. A large majority of patients were hospitalized for a first-time cancer (80.8%), type invasive ductal carcinoma (70.8%) and were receiving surgery as primary treatment (45%). Furthermore, 30.8% of the women reported tobacco consumption and 38.4% high-risk alcohol consumption. Regarding mental health, 40.8% presented moderate to intense levels of psychological distress. No significant relationships were found between consumption scores and sociodemographic, medical or psychological characteristics. Only the patient's age was negatively associated with tobacco consumption. Tobacco and at-risk alcohol consumption are frequently reported behaviors during breast cancer treatment. Intervention strategies targeting risk behaviors related to addictive consumption should be implemented during the full treatment of breast cancer patients.

A Novel Immobilization Method Using 3D Printing for the Treatment of Head and Neck Cancer

<h3>Purpose/Objective(s)</h3> Radiation therapy requires immobilization hardware that may produce significant anxiety for a patient under treatment, particularly when covering the face. In cases where such anxiety is treatment limiting, 3D printing can provide for a better tolerated custom immobilization. The technical hurdles, fidelity of positioning, and clinical outcomes are reviewed for the treatment of oropharyngeal cancer in a patient who was unable to tolerate traditional mask-based immobilization. <h3>Materials/Methods</h3> A 3D printer was used to create a custom immobilization cradle for the treatment of squamous cell carcinoma of the oropharynx. This was used in the treatment of a patient who was unable to be simulated despite nine separate attempts, using a variety of open-faced immobilization techniques, anxiolytics, and coaching. Operative management was not feasible due to the patient's habitus and comorbidities. Despite acknowledging the severity of the situation, the patient could not complete simulation. Thus, after he was confirmed to still have locoregionally limited disease, we proposed creation of a 3D-printed cradle for the back of his head and neck, based on CT imaging without immobilization. Three separate attempts were made to complete the printing of the cradle. Major issues stemmed from the need to find a set of support structures that would allow for the proper printing of the area supporting the ears, as well as the back of the head. Ultimately, a dense array of column supports was successful, but still required buttressing of the columns with tape at several points during the print. In total, 664g of polylactic acid filament was used, as well as 525g of polyvinyl alcohol, a water soluble support material. Total print time was just under 78 hours for the final successful print. <h3>Results</h3> The patient was able to tolerate simulation and the full course of fractionated chemoradiotherapy. The cradle provided for a setup requiring mean absolute shift of 0.35 mm in the anterior-posterior direction, 0.17 cm in the cranio-caudal direction, and 0.36 cm in the lateral direction, and a couch kick of 1.28 degrees to bring the patient into alignment on final imaging. The patient is currently in stable condition and following up with both medical oncology and radiation oncology at regular intervals. Imaging and laryngoscopy, conducted at multiple time points following completion, shows him to have no evidence of disease, now at 10 months. <h3>Conclusion</h3> The full uses of 3D printing are still developing, as evidenced by the difficulty of creating a workable print, both in terms of prototyping and the time needed to create a print. The impact of 3D printing within the context of radiation oncology, as well as in other specialties, will undoubtedly continue to increase the variety of viable treatment options available to patients as the technology improves.

Experienced quality of care and emotional functioning of patients with advanced cancer and their relatives: Results of a multicenter observational cohort study (eQuiPe).

3 Background: Previous studies on experienced quality of care and quality of life have not addressed the reciprocal relation between patients and their relatives. For the first time we were able to include almost 700 couples (patient – relative) in a palliative oncological care context. This study aims to assess the experienced quality of care and emotional functioning (EF) of patients with advanced cancer and their relatives, including their reciprocal relation by using a dyadic approach. Methods: A prospective multicentre observational study among patients with advanced cancer and their relatives, recruited from 40 hospitals in the Netherlands or self-enrolled between November 2017 and January 2020 (eQuiPe study). Patients with metastatic cancer and their relatives were eligible to participate. Respondents completed a questionnaire and clinical data of the patient were obtained by linking the information to the Netherlands Cancer Registry (NCR). Logistic regression analyses were performed on baseline data of 1,103 patients and 831 relatives to assess the association between experienced quality of care and EF of patients and relatives separately and across dyads. Results: In total, 1,103 (65%) patients and 831 (71%) relatives completed the baseline questionnaire, including 699 unique patient-relative couples. Patients experienced lower levels of quality of life, including EF, and more symptoms compared to the normative population ( p&lt;.001). Relatives reported even clinically relevantly lower EF compared to patients (69 vs. 78, p&lt;.001) and were less satisfied with care (59 vs. 74; p&lt;.001). Being more satisfied with care in general ( p&lt;.05) and clarity about who their central health care professional ( p&lt;.05) were positively associated with high EF in patients. For relatives, perceived continuity of care ( p&lt;.01) and continuity of information for the patient ( p&lt;.05) were positively associated with high EF. Dyadic analyses showed that EF of patients ( p&lt;.001) and relatives ( p&lt;.001) was positively associated with EF of the other person and perceived continuity of care by relatives was positively associated with high EF in patients ( p&lt;.01). Conclusions: Experienced integral organisation and satisfaction with care in patients and relatives are related to their EF. The additional reciprocal relation between patients’ and their relatives’ EF and the experienced continuity of care suggests the opportunity for a family‐centered approach to optimize advanced cancer care.

Preliminary Results of the "Capasquelet" Technique for Managing Femoral Bone Defects-Combining a Masquelet Induced Membrane and Capanna Vascularized Fibula with an Allograft.

We describe the preliminary results of a novel two-stage reconstruction technique for extended femoral bone defects using an allograft in accordance with the Capanna technique with an embedded vascularized fibula graft in an induced membrane according to the Masquelet technique. We performed what we refer to as “Capasquelet” surgery in femoral diaphyseal bone loss of at least 10 cm. Four patients were operated on using this technique: two tumors and two traumatic bone defects in a septic context with a minimum follow up of one year. Consolidation on both sides, when achieved, occurred at 5.5 months (4–7), with full weight-bearing at 11 weeks (8–12). The functional scores were satisfactory with an EQ5D of 63.3 (45–75). The time to bone union and early weight-bearing with this combined technique are promising compared to the literature. The osteoinductive role of the induced membrane could play a positive role in the evolution of the graft. Longer follow up and a larger cohort are needed to better assess the implications. Nonetheless, this two-stage technique appears to have ample promise, especially in a septic context or in adjuvant radiotherapy in an oncological context.

#GYNONC: are we missing opportunities to reach our patients?

<h3>Objectives:</h3> Social media outlets have increased in popularity within the last decade and are influencing the ways in which patients interact with the healthcare system. Daily use among adults in the US is reported as 63% for Instagram and 42% for Twitter. While social media increasingly serves as a medium for conversation between patients and their providers, the use by Gynecologic Oncology providers has not been described. The purpose of this study is to examine the presence of designated NCI-designated Cancer Centers' Gynecology Oncology divisions on social media and to characterize the content posted by them. <h3>Methods:</h3> The 71 NCI-Designated cancer centers and their Gynecology Oncology divisions were searched on both Instagram and Twitter. Search was performed using the cancer center names independently and in gynecology oncology context. Once a social media account was identified, information about number of followers and posts was recorded, and content was reviewed and divided into categories including: marketing, patient education and awareness, patient engagement, clinical and research updates and fellowship recruitment. <h3>Results:</h3> Of 71 NCI-Designated Cancer Centers, 29 (40.8%) had Instagram accounts and 64 (90.1%) had twitter accounts with a range of 17-101,000 followers. When searched on Instagram, 4 (6%) Gynecology Oncology divisions had Instagram accounts with number of followers ranging from 60-219 and average number of posts of 32. When searched for Gynecology Oncology divisions on Twitter, 8 (12%) departments were identified with a range of 0-791 followers and average of 110 posts. When analyzing the content of Gynecology Oncology Divisions social media accounts, 5 used their account for marketing, 4 for patient education and awareness, 1 for patient engagement, 4 for clinical and research updates and 3 for fellowship recruitment (Table1). <h3>Conclusions:</h3> Social media has become a powerful form of communication and engagement. While 90% of NCI-designated Cancer Centers have social media presences, Gynecology Oncology divisions are under-utilizing this medium to reach and educate patients. Greater participation by gynecology oncologists may increase patient education, raise awareness and engagement.

Antisense Oligonucleotide-Based Therapeutic against Menin for Triple-Negative Breast Cancer Treatment.

The tumor suppressor menin has dual functions, acting either as a tumor suppressor or as an oncogene/oncoprotein, depending on the oncological context. Triple-negative breast cancer (TNBC) is characterized by the lack of expression of the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (ERBB2/HER2) and is often a basal-like breast cancer. TNBC is associated with a dismal prognosis and an insufficient response to chemotherapies. Previously, menin was shown to play a proliferative role in ER-positive breast cancer; however, the functions of menin in TNBC remain unknown. Here, we have demonstrated that menin is expressed in various TNBC subtypes with the strongest expression in the TNBC Hs 578T cells. The depletion of menin by an antisense oligonucleotide (ASO) inhibits cell proliferation, enhances apoptosis in Hs 578T cells, highlighting the oncogenic functions of menin in this TNBC model. ASO-based menin silencing also delays the tumor progression of TNBC xenografts. Analysis of the menin interactome suggests that menin could drive TNBC tumorigenesis through the regulation of MLL/KMT2A-driven transcriptional activity, mRNA 3′-end processing and apoptosis. The study provides a rationale behind the use of ASO-based therapy, targeting menin in monotherapy or in combination with chemo or PARP inhibitors for menin-positive TNBC treatments.

The Role of microRNA Let-7d in Female Malignancies and Diseases of the Female Reproductive Tract.

microRNAs are small noncoding RNAs that regulate gene expression at the posttranscriptional level. Let-7d is a microRNA of the conserved let-7 family that is dysregulated in female malignancies including breast cancer, ovarian cancer, endometrial cancer, and cervical cancer. Moreover, a dysregulation is observed in endometriosis and pregnancy-associated diseases such as preeclampsia and fetal growth restriction. Let-7d expression is regulated by cytokines and steroids, involving transcriptional regulation by OCT4, MYC and p53, as well as posttranscriptional regulation via LIN28 and ADAR. By downregulating a wide range of relevant mRNA targets, let-7d affects cellular processes that drive disease progression such as cell proliferation, apoptosis (resistance), angiogenesis and immune cell function. In an oncological context, let-7d has a tumor-suppressive function, although some of its functions are context-dependent. Notably, its expression is associated with improved therapeutic responses to chemotherapy in breast and ovarian cancer. Studies in mouse models have furthermore revealed important roles in uterine development and function, with implications for obstetric diseases. Apart from a possible utility as a diagnostic blood-based biomarker, pharmacological modulation of let-7d emerges as a promising therapeutic concept in a variety of female disease conditions.

On the predictability of postoperative complications for cancer patients: a Portuguese cohort study

Postoperative complications are still hard to predict despite the efforts towards the creation of clinical risk scores. The published scores contribute for the creation of specialized tools, but with limited predictive performance and reusability for implementation in the oncological context. This work aims to predict postoperative complications risk for cancer patients, offering two major contributions. First, to develop and evaluate a machine learning-based risk score, specific for the Portuguese population using a retrospective cohort of 847 cancer patients undergoing surgery between 2016 and 2018, for 4 outcomes of interest: (1) existence of postoperative complications, (2) severity level of complications, (3) number of days in the Intermediate Care Unit (ICU), and (4) postoperative mortality within 1 year. An additional cohort of 137 cancer patients from the same center was used for validation. Second, to improve the interpretability of the predictive models. In order to achieve these objectives, we propose an approach for the learning of risk predictors, offering new perspectives and insights into the clinical decision process. For postoperative complications the Receiver Operating Characteristic Curve (AUC) was 0.69, for complications’ severity AUC was 0.65, for the days in the ICU the mean absolute error was 1.07 days, and for 1-year postoperative mortality the AUC was 0.74, calculated on the development cohort. In this study, predictive models which could help to guide physicians at organizational and clinical decision making were developed. Additionally, a web-based decision support tool is further provided to this end.