Anticancer Drugs-Related Hypogonadism in Male Patients with Advanced Cancers on Active Treatment: A Systematic Review.

BACKGROUND: In male patients with cancer treated with antineoplastic drug, hypogonadism is a neglected cause of diminished quality of life. This condition may be cancer related as well as toxicity related. The role of antineoplastic drug in causing hypogonadism is poorly understood. The aim of this systematic review was to establish the prevalence, nature (primary/secondary), and impact of hypogonadism on quality of life in male patients with cancer on antineoplastic therapy. METHODS: The search strategy used PubMed, Embase, and Cochrane databases to select articles in English language that described hypogonadism in male patients with cancer. The search period was from January 1, 1945 to February 28, 2023. We included observational studies, case reports or case series and excluded studies concerning hematological malignancies, prostate cancer, female patients, and survivors. FINDINGS: Of 4488 records identified, 28 studies met inclusion criteria (17 observational studies, 11 case reports or case series). Anti-angiogenic drugs and crizotinib were found to have a role in the development of hypogonadism. Patients treated with immune checkpoint-inhibitors developed secondary hypogonadism due to immune-related hypophysitis or orchitis. As for active chemotherapy, platinum salts were often associated with hypogonadism, followed by antimetabolites and taxanes. Selected studies were heterogeneous for populations, interventions, and outcomes assessments. Thus, a generalization is difficult. Moreover, the role of concurrent etiologies cannot be excluded in most studies. CONCLUSION: Our research emphasizes the importance of evaluating the gonadal axis before treatment in patients considered at risk and testing it at regular intervals or in case of clinical suspicion.

Regorafenib in advanced solitary fibrous tumour: Results from an exploratory phase II clinical study.

BACKGROUND: To investigate the activity of regorafenib in advanced solitary fibrous tumour (SFT). METHODS: An Italian monocentric investigator-initiated exploratory single-arm Phase II trial was conducted of regorafenib in adult patients with advanced and progressive SFT, until progression or limiting toxicity. Prior treatment with antiangiogenics was allowed. Primary and secondary end-points were: overall response rate (ORR) by Choi criteria, and ORR by RECIST, progression-free survival (PFS), overall survival (OS). RESULTS: From January 2016 to February 2021, 18 patients were enroled [malignant-SFT = 13; dedifferentiated-SFT (D-SFT) = 4; typical-SFT (T-SFT) = 1]. Fourteen patients were pre-treated, in 12 cases with antiangiogenics (median [m-] lines of treatment = 3). Sixteen patients were evaluable for response (one screening failure; one early discontinuation). Six/16 (35.2%) required a definitive dose reduction. ORR by Choi was 37.5% (95% CI: 15.2-64.6), with 6/16 (37.5%) partial responses (PR), 6/16 (37.5%) stable disease (SD) and 4/16 (25%) progressions; 5/6 responses occurred in patients pre-treated with antiangiogenics. No responses were detected in D-SFT. Best RECIST responses were: 1/16 (6.2%) PR, 12/16 (75%) SD, 3/16 (18.8%) progressions. At 48.4 month m-FU, m-PFS by Choi was 4.7 (inter-quartile range: 2.4-13.1) months, with 31.2% patients progression-free at 1 year. CONCLUSION: Regorafenib showed activity in SFT, with 30% patients free-from-progression at one year. Responses were observed also in patients pretreated and refractory to another antiangiogenic agents. However, ORR and m-PFS were lower than reported with other antiangiogenics, and this was possibly due to discrepancies in the patient population and the high-rate of dose reductions.

A real-world study on the prevalence and risk factors of medication related osteonecrosis of the jaw in cancer patients with bone metastases treated with Denosumab.

AIM: Assessing the incidence of Medication Related Osteonecrosis of the Jaw (MRONJ) in cancer patients with bone metastases receiving Denosumab (Dmab) and identifying potential risk factors. METHODS: A retrospective observational study on consecutive cancer patients with bone metastases, who received at least one dose of Dmab and one follow-up visit. MRONJ crude cumulative incidence (CCI) was estimated considering death without MRONJ as competing event. Multiple regression models were used to study the association between MRONJ incidence and potential risk factors: age, cancer diagnosis, previous bisphosphonates, dental treatments before starting Dmab, extraction or other dental treatment during Dmab, chemotherapy, hormone therapy, and antiangiogenic (AA) agents concurrent use. RESULTS: On 780 patients included (median follow-up 17 months), 54% and 18% had, respectively, breast and prostate cancer. The mean number of Dmab administration was 12. Fifty-six patients developed MRONJ with a 24- and a 48-month crude cumulative incidence of 5.7% (95% Cl: 4.2%-7.8%) and 9.8% (95% CI: 7.6%-12.7%), respectively. Higher MRONJ incidence was significantly associated with middle aged group (>56 and ≤73), both at univariate and multivariate analysis (p = 0.029 and 0.0106). Dental treatments (Hazard Ratio [HR] = 3.67; p = 0.0001), dental extractions (HR = 23.40; p < 0.0001), and previous BP administration (HR = 2.62; p = 0.0024) were significantly associated with higher MRONJ incidence at multivariate Cox analysis. Although not statistically significant, MRONJ incidence was lower for patients receiving chemotherapy or hormone therapy and higher for those receiving AAs. CONCLUSIONS: The results confirm a clinically relevant incidence of Dmab-induced MRONJ. Dental treatments, especially extraction, during and before Dmab, constitute a serious risk factor. The role of AA concurrent administration deserves further investigations.

Outpatient palliative care referral system (PCRS) for patients with advanced cancer: an impact evaluation protocol.

INTRODUCTION: Early palliative care (PC) in the clinical pathway of advanced cancer patients improves symptom control, quality of life and has a positive impact on overall quality of care. At present, standardised criteria for appropriate referral for early PC in oncology care are lacking. The aim of this project is to develop a set of standardised referral criteria and procedures to implement appropriate early PC for advanced cancer patients (the palliative care referral system, PCRS) and test its impact on user perception of quality of care received, on patient quality of life and on the use of healthcare resources. SETTING: Selected oncology clinics and PC outpatient clinic. METHODS AND ANALYSIS: A scoping literature review and an expert consultation through a nominal group technique will be used to revise existing referral tools and to develop a new one, the PCRS. 25 patients will be enrolled in a pilot study to assess feasibility of the implementation of PCRS; 10 interviews with patients and healthcare professionals will be carried out to evaluate applicability.A pretest-post-test quasiexperimental study involving 150 patients before implementation of the PCRS and 150 patients after implementation will be carried out.Patient satisfaction with care received, quality of life and use of resources, and caregiver satisfaction with care will also be assessed to explore the impact of the intervention. ETHICS AND DISSEMINATION: Ethical approval for the study has been granted by the Institutional Review board of the Fondazione IRCCS Istituto Nazionale Tumori; approval reference INT201/19.Results will be disseminated through open access publications and through scientific communication presented at national and international conferences. TRIAL REGISTRATION NUMBER: NCT04936568.

Managing Care during the COVID-19 Pandemic: The Point of View and Fears of Pediatric Cancer Patients' Families.

(1) Background: When the COVID-19 pandemic arrived, changes had to be made to several management aspects at our Pediatric Oncology Unit. We investigated how the families perceived these changes. (2) Methods: Two questionnaires were developed at the Pediatric Oncology Unit of the Istituto Nazionale dei Tumori in Milan in order to explore how the pandemic had affected the experience of patients who had been or were being treated at our hospital, as well as their families. These questionnaires were administered to three groups of individuals. (3) Results: Between July and October 2020, 120 questionnaires were administered to parents of patients. The impact of school closures and the impossibility of attending sports and social activities outside the hospital were regarded as important, and it was reported that 77.5% of parents judged social distancing to have affected their children. Regarding the changes introduced in the management of the ward and outpatient clinic, most parents' opinions were positive. Differences in the opinions expressed by Groups 2 and 3 were statistically significant on the topics of relationships in the ward and staff workload. The aspect most negatively affected by the pandemic was the support that patients' parents were able to give each other. Regardless of whether patients were treated before the pandemic or after the first lockdown, all parents indicated strong degrees of satisfaction with the care received and the organizational arrangements. (4) Conclusions: The results of our study point us in the right direction to further improve our daily work and better respond to the needs of our patients and their families.

sFlt-1/PlGF ratio in hypertensive disorders of pregnancy in patients affected by COVID-19.

OBJECTIVES: To analyze soluble Fms-like tyrosine Kinase 1 (sFlt-1) and Placental Growth Factor (PlGF) ratio concentrations in COVID-19 pregnant patients with and without Hypertensive Disorders of Pregnancy (HDP), compared with non COVID-19 pregnant patients with HDP and a control group. STUDY DESIGN: We recruited and obtained a complete follow-up of 19 COVID-19 pregnant patients with HDP and of 24 COVID-19 normotensive pregnant patients. Demographic, clinical and sFlt-1/PlGF ratio findings were compared with a group of 185 non COVID-19 pregnant patients with HDP and 41 non COVID normotensive patients. Findings were based on univariate analysis and on a multivariate adjusted model, and a case by case analysis of COVID-19 pregnant patients with an abnormal sFlt-1/PlGF ratio > 38 at recruitment. MAIN OUTCOME MEASURES: sFlt-1/PlGF ratio. RESULTS: We confirmed a significant higher prevalence of HDP in women affected by COVID-19 compared to control population. sFlt-1/PlGF ratio was found high in HDP patients, with and without of Sars-Cov2 infection. COVID-19 patients with worse evolution of the disease showed greater rates of obesity and other comorbidities. sFlt/PlGF ratio proved not to be helpful in the differential diagnosis of the severity of this infection. CONCLUSIONS: COVID-19 pregnant patients showed a higher prevalence of HDP compared to non COVID-19 controls, as well as higher comorbidity rates. In spite of the possible common endothelial target and damage, between Sars-Cov-2 infection and HDP, the sFlt1/PlGF ratio did not correlate with the severity of this syndrome.

The sFlt-1/PlGF Ratio in Patients Affected by Gestational Diabetes and SARS-CoV-2 Infection.

Low values of the ratio of plasmatic soluble blocking factor FMS-like tyrosine Kinase 1 and placental growth factor (sFlt-1/PlGF) are required for an adequate placental angiogenesis and function. It has been shown that patients affected by gestational diabetes (GD) and patients with pneumonia from SARS-CoV-2 are characterized by an increased sFlt-1/PlGF ratio. The aim of the present study was to evaluate the sFlt-1-PlGF ratio in pregnancies complicated by COVID-19 and GD. We compared the plasmatic sFlt-1/PlGF ratio among the following groups of pregnant women: COVID-19, GD patients; COVID-19, non-GD patients; non-COVID-19, GD patients; and non-COVID-19, non-GD controls. We enrolled 62 women in the present study, who were divided as follows: 14 COVID-19, GD patients; 12 COVID-19, non-GD patients; 11 non-COVID-19, GD patients; and 25 non-COVID-19, non-GD controls. The COVID-19, GD patients presented a higher pre-pregnancy BMI, a higher prevalence of hypertensive disorders of pregnancy as a co-morbidity, and an increased need for medication for their diabetes. Neonatal data were similar between the groups. The controls showed a significantly lower sFlt-1/PlGF ratio compared to pregnancies complicated by GD and SARS-CoV-2 infection. The sFlt-1/PlGF ratio was higher in patients affected by both GD and SARS-CoV-2 infection; these subjects were characterized by a greater incidence of obesity and hypertensive disorders of pregnancy.

Non-invasive Maternal Hemodynamic Assessment to Classify High-Risk Pregnancies Complicated by Fetal Growth Restriction.

Objectives: To verify whether the use of the temporal criterion of 32 weeks' gestation is effective in identifying maternal hemodynamic differences between early- and late-onset fetal growth restriction (FGR), and to test the statistical performance of a classificatory algorithm for FGR. Materials and methods: A prospective multicenter study conducted at three centers over 17 months. Singleton pregnant women with a diagnosis of FGR based on the international Delphi survey consensus at ≥ 20 weeks of gestation were included. FGR was classified as early-onset if diagnosed <32 weeks' gestation and as late-onset if ≥32 weeks. Hemodynamic assessment was performed by USCOM-1A at the time of FGR diagnosis. Comparisons between early- and late-onset FGR among the entire study cohort, FGR associated with hypertensive disorders of pregnancy (HDP-FGR), and isolated FGR (i-FGR) were performed. In addition, HDP-FGR cases were compared to i-FGR, regardless of the temporal cut-off of 32 weeks' gestation. Finally, a classificatory analysis based on the Random Forest model was performed to identify significant variables with the ability to differentiate FGR phenotypes. Results: During the study period, 146 pregnant women fulfilled the inclusion criteria. In 44 cases, FGR was not confirmed at birth, thus limiting the final study population to 102 patients. In 49 (48.1%) women, FGR was associated to HDP. Fifty-nine (57.8%) cases were classified as early-onset. Comparison of the maternal hemodynamics between early- and late-onset FGR did not show any difference. Similarly, non-significant findings were observed in sensitivity analyses performed for HDP-FGR and for i-FGR. In turn, comparison between pregnant women with FGR and hypertension and women with i-FGR, independently of the gestational age at FGR diagnosis, revealed substantial differences, with the former showing higher vascular peripheral resistances and lower cardiac output, among other significant parameters. The classificatory analysis identified both phenotypic and hemodynamic variables as relevant in distinguishing HDP-FGR from i-FGR (p=0.009). Conclusions: Our data show that HDP, rather than gestational age at FGR diagnosis, allows to appreciate specific maternal hemodynamic patterns and to accurately distinguish two different FGR phenotypes. In addition, maternal hemodynamics, alongside phenotypic characteristics, play a central role in classifying these high-risk pregnancies.