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Purpose Pasireotide is the first pituitary-directed approved therapy for Cushing’s disease (CD), effective in reducing 24 h urine free cortisol (UFC) > 50% in more than half of patients, with beneficial effects and with a relatively high incidence of hyperglycemia. The aim of this study was to evaluate efficacy and safety of long-term treatment with pasireotide (PAS) in CD patients, also according to gender. Methods We retrospectively evaluated 19 consecutive CD patients (13F; age at diagnosis: 34.9 ± 11.7 yrs) treated with PAS, referred to and followed-up at the Endocrine Unit of the University Hospital of Messina, from 2013 to 2023. We evaluated and compared, in the whole cohort and after gender stratification, anthropometric, clinical, neuroradiological, hormonal and metabolic parameters, along with CD-related comorbidities, before PAS treatment and at last follow-up visit. Side-effects and adverse events related to treatment were also assessed. Results Under PAS treatment: overall, 52.6% of patients achieved a normalization of UFCxULN from baseline without any difference in terms of UFC reduction and/or response to treatment according to gender; two females out of the 19 patients experienced tumor shrinkage. In the whole cohort, at last follow-up visit as compared to baseline: body weight, BMI, total cholesterol, LDL-cholesterol were significantly improved, while HbA1c significantly increased. Prevalence of CD-related comorbidities did not change significantly, while the number of patients with IGF-1 SDS below the sex/age adjusted normal range significantly increased. Stratifying patients by sex, at last follow-up visit vs. baseline, we observed lower total and LDL-cholesterol in men and lower waist circumference in women. Most common adverse events were related to hyperglycemia which led to treatment withdrawal in 3 cases, without any gender difference. Response to PAS correlated with younger age at diagnosis, longer duration of disease, lower Hb1Ac levels and absence of diabetes at baseline. Conclusion: PAS is effective in a significant number of patients with CD, regardless of gender, having a positive impact on lipid profile and on anthropometric parameters. Major adverse events are related to hyperglycemia which is more frequently associated with a worse baseline glycometabolic and lipid profile in both sexes.

Cancer is the second leading cause of death in the western world. In the era of precision medicine, a significant number of cancer patients can be cured with several anti-cancer therapeutic regimens. However, therapy failure may be caused by treatment side effects, such as diarrhea, especially occurring in patients with gastrointestinal or pelvic malignancies. In particular, diarrhea is one of the most frequent gastrointestinal toxicity during cancer treatment and it can result from nearly bot chemo- and radio-therapeutic strategies currently used. Diarrhea has a serious impact on patients' quality of life and treatment dosing and schedule modification due to its severity can negatively influence treatment outcomes. In this context, probiotics may play an interesting role in several human diseases with an inflammatory bowel involvement and, among these, GG (LGG) is one of the most characterized and utilized. In particular, LGG is able to reverse intestinal dysbiosis and moderate diarrhea. Moreover, preclinical studies have documented its effects in reducing chronic inflammation associated with cancer development. This review summarizes the preclinical results of LGG on cancer cells proliferation and tumor invasion as well as the potential role of LGG use in cancer patients for the prevention and management of diarrhea associated with cancer treatment. Overall, these encouraging data support further investigation on the use of LGG in stratified patients undergoing specific therapeutic protocols, including chemotherapy and pelvic radiotherapy, in order to reduce the development of severe diarrhea and thus improve the adherence to the therapy and patients' quality of life.

Endogenous Cushing’s syndrome (CS) is rare, with an incidence of 0.7–2.4 per million population per year according to population-based studies. However, evaluation of patients presenting disorders potentially related to cortisol excess, and therefore with a ‘high risk of clinical suspicion’ profile, could bring out several unrecognized cases. CS represents one of the most challenging endocrine diseases, with clinical features overlapping with those of common conditions affecting general population, invariably resulting in potential mis- or delayed diagnosis with negative consequences in terms of morbidity and mortality. CS is remarkably prevalent among young females, variably presenting with menstrual irregularities and/or signs and symptoms of hyperandrogenism. Herein we briefly reviewed literature on prevalence and clinical impact of menses abnormalities, acne and hirsutism -also coexisting in the context of a polycystic ovary syndrome- in CS, aiming at clarifying if, when and how to screen for hypercortisolism young women with these disorders.

Purpose scientific literature highlights risk factors linked to the onset of psychopathology in different medical pathological contexts. Acromegaly is a rare condition, particularly noteworthy due to the associated clinical psychological features. This research aimed at understanding the main psychopathological outcomes related to acromegaly, with particular emphasis to anxiety and depression. Methods In January 2024, in line with PRISMA guidelines, a systematic search based on PubMed, Scopus, Web of Science and PsycInfo was conducted to detect studies considering anxiety, depression and alexithymia in patients suffering from acromegaly. The Keywords used for the search phase were “Acromegaly” AND “Depression” OR “Anxiety” OR “Alexithymia”. Results Fifty-five studies were eligible. Anxiety and depression were significantly present in patients with acromegaly, with prevalence rates variable based on disease status and psycho-diagnostic instruments. None of the included studies reported alexithymia in patients with acromegaly. No significant difference was found regarding anxiety and depressive symptoms in patients with acromegaly in comparison with patients suffering from different pituitary diseases and chronic conditions. Anxiety and depression were associated with lower perceived HR-QoL, presence of comorbidity, joint issues, delayed diagnosis, disease duration and body image concerns. Conclusions Anxiety and depression may be encountered in patients with acromegaly, impacting HR-QoL and the course of the disease. This systematic review suggests that a deeper evaluation of clinical psychological features in patients suffering from acromegaly is needed. Particularly, the early detection of clinical psychological symptoms may lead to multi-integrate interventions promoting individuals’ well-being and a better HR-QoL.

We conducted a large, multicenter, retrospective survey aimed to explore the impact of tumor bone involvement in Non-Small Cell Lung Cancer.Data on clinical-pathology, skeletal outcomes and bone-directed therapies for 661 deceased patients with evidence of bone metastasis were collected and statistically analyzed. Bone metastases were evident at diagnosis in 57.5% of patients. In the remaining cases median time to bone metastases appearance was 9 months. Biphosphonates were administered in 59.6% of patients. Skeletal-related events were experienced by 57.7% of patients; the most common was the need for radiotherapy. Median time to first skeletal-related event was 6 months. Median survival after bone metastases diagnosis was 9.5 months and after the first skeletal-related event was 7 months. We created a score based on four factors used to predict the overall survival from the diagnosis of bone metastases: age >65 years, non-adenocarcinoma histology, ECOG Performance Status >2, concomitant presence of visceral metastases at the bone metastases diagnosis. The presence of more than two of these factors is associated with a worse prognosis.This study demonstrates that patients affected by Non-Small Cell Lung Cancer with bone metastases represent a heterogeneous population in terms of risk of skeletal events and survival.

Abstract Context Because of the rarity of adrenocortical cancer (ACC), only a few population-based studies are available, and they reported limited details in the characterization of patients and their treatment. Objective To describe in a nationwide cohort the presentation of patients with ACC, treatment strategies, and potential prognostic factors. Methods Retrospective analysis of 512 patients with ACC, diagnosed in 12 referral centers in Italy from January 1990 to June 2018. Results ACC diagnosed as incidentalomas accounted for overall 38.1% of cases, with a frequency that increases with age and with less aggressive pathological features than symptomatic tumors. Women (60.2%) were younger than men and had smaller tumors, which more frequently secreted hormones. Surgery was mainly done with an open approach (72%), and after surgical resection, 62.7% of patients started adjuvant mitotane therapy. Recurrence after tumor resection occurred in 56.2% of patients. In patients with localized disease, cortisol secretion, ENSAT stage III, Ki67%, and Weiss score were associated with an increased risk of recurrence, whereas margin-free resection, open surgery, and adjuvant mitotane treatment were associated with reduced risk. Death occurred in 38.1% of patients and recurrence-free survival (RFS) predicted overall survival (OS). In localized disease, age, cortisol secretion, Ki67%, ENSAT stage III, and recurrence were associated with increased risk of mortality. ACCs presenting as adrenal incidentalomas showed prolonged RFS and OS. Conclusion Our study shows that ACC is a sex-related disease and demonstrates that an incidental presentation is associated with a better outcome. Given the correlation between RFS and OS, RFS may be used as a surrogate endpoint in clinical studies.

In addition to identifying alterations suitable for molecularly targeted therapy (TT), comprehensive genomic profiling (CGP) may convey prognostic/predictive information in advanced non-small-cell lung cancer (aNSCLC). We investigated the impact of tumor suppressor gene alterations (TSGAs) on aNSCLC patients’ outcome in a real-world setting. The IMMINENT clinical-genomic database, which provides data on molecular and clinico-pathological features, treatment history, and patients’ outcomes of aNSCLC patients who underwent CGP using tissue- or blood-based next-generation sequencing (NGS) between May 2019 and November 2022 was interrogated to assess overall (OS) and progression-free survival (PFS). The Cox proportional hazard model was used to assess the prognostic and predictive role of genomic features. Two hundred and one patients were included in the analysis. Genomic alterations in STK11, KEAP1 , and MYC were associated with poorer OS, while ALK alterations were associated with better OS; after adjustment, STK11 and KEAP1 alterations retained their independent negative prognostic impact. Moreover, KRAS:STK11 and KRAS:KEAP1 co-mutations cooperated to negatively influence OS. In terms of predictive performance, CDKN2A/B alterations predicted worse PFS on chemotherapy (CT) and TP53 alterations predicted worse PFS on TT, while both CDKN2A/B and TP53 , as well as KRAS , alterations predicted better PFS on immunotherapy (IO). Extended CGP, encompassing TSGAs, provides valuable prognostic and predictive insights for aNSCLC, thereby adding to the mere identification of potential targets for TT. Our findings also underline the complexity of the lung cancer molecular landscape and suggest the need for studying a personalized therapeutic approach in patients with TSGAs.

BackgroundLow-grade serous ovarian and peritoneal cancer (LGSC) is a rare disease and few data on the clinical and genomic landscape have been published.MethodsA retrospective analysis of patients diagnosed with LGSC between 1996 and 2019 was conducted in MITO centers. Objective Response Rate (ORR) to treatments, progression-free survival (PFS) and overall survival (OS) were assessed. Additionally, the tumor molecular profile of 56 patients was evaluated using the Next Generation Sequencing (NGS) FoundationOne CDX (Foundation Medicine®).ResultsA total of 128 patients with complete clinical data and pathologically confirmed diagnosis of LGSC were identified. ORR to first and subsequent therapies were 23.7% and 33.7%, respectively. PFS was 43.9 months (95% CI:32.4–53.1) and OS was 105.4 months (95% CI: 82.7–not reached). The most common gene alterations were: KRAS (n = 12, 21%), CDKN2A/B (n = 11, 20%), NRAS (n = 8, 14%), FANCA (n = 8, 14%), NF1 (n = 7, 13%) and BRAF (n = 6, 11%). Unexpectedly, pathogenetic BRCA1 (n = 2, 4%), BRCA2 (n = 1, 2%) and PALB2 (n = 1, 2%) mutations were found.ConclusionsMITO 22 suggests that LGSC is an heterogenous disease for both its clinical behavior in response to standard therapies and its molecular alterations. Future prospective studies should test treatments according to biological and molecular tumor’s characteristics.Clinical trial registrationThis study is registered under NCT02408536 on ClinicalTrials.gov.

PurposeThe evaluation of skeletal fragility in Cushing’s syndrome (CS) is a clinical challenge, since dual-energy X-ray absorptiometry (DXA) does not capture abnormalities in bone microstructure induced by glucocorticoid excess. Hypercortisolism was shown to increase bone marrow adiposity, but it is still unknown whether high bone marrow fat (BMF) as measured by vertebral magnetic resonance spectroscopy may predict fracture risk in this clinical setting. In this cross-sectional study, we evaluated the association between BMF and vertebral fractures (VFs) in patients with CS.MethodsTwenty patients (5 M, age 44 ± 13 years) with active CS were evaluated for morphometric VFs, lumbar spine BMF, and bone mineral density (BMD). Fifteen healthy volunteers (4 M, age 43 ± 12 years) acted as control group for BMF evaluation.ResultsBMF was significantly higher in CS patients vs. controls (52.0% vs. 27.0%, p < 0.01), and was directly correlated with patients’ age (p = 0.03), 24-hours urine-free cortisol (p = 0.03), midnight serum cortisol (p = 0.02), and serum CTX (p = 0.01). Patients with VFs (13 cases) showed significantly higher BMF vs. patients without VFs (65.0% vs. 24.0%, p = 0.03). Fractured patients with either normal BMD or osteopenia showed comparable BMF to fractured patients with either osteoporosis or low BMD for age (p = 0.71). When the analysis was restricted to patients with normal BMD or osteopenia, VFs were still significantly associated with higher BMF (p = 0.05).ConclusionsThis study provides a first evidence that vertebral adiposity may be a marker of hypercortisolism-induced skeletal fragility and measurement of spine BMF could have a role in the diagnostic work-up for the assessment of fracture risk in CS.

Background: In real-world practice, eribulin mesylate provides significant survival benefit, with a manageable safety profile in heavily pretreated patients with metastatic breast cancer (MBC). Methods: In this prospective, open-label, multicentre, observational study we evaluated the effectiveness and tolerability of eribulin as third-line treatment in a homogeneous population. The primary endpoints were the safety profile and response in metastatic sites; secondary endpoints included the response in different subtypes, overall response rate (ORR), progression-free survival (PFS) and overall survival (OS). Results: From 2013 to 2016, 118 women were treated in 21 Sicilian institutions; the median age was 58 years (range 29–79), with 69% of patients under 65. The median cycles of eribulin were 5.5 (range 1–26). The most common adverse event was neutropenia (9.3%, 3 cases of grade 3, 4 of grade 4); only 1 case of QT prolongation was reported. Eribulin was effective in controlling metastatic disease in all sites, and it achieved the highest ORR in brain (16%) and liver (14.9%). Median OS was 31.8 months (95% CI 27.9–34.4) and median PFS 5.5 months (95% CI 4.2–6.6). PFS was 5.2 months (95% CI 2.8–8.4) in patients with triple-negative subtype. Median PFS was longer in patients over 65 years (6.1 months, 95% CI 4.4–8.3). In patients who had visceral metastases PFS was 5.5 months (95% CI 95% 3.5–6.6) and OS 33.9 months (95% CI 29.8–40.8). Conclusions: Eribulin as third-line treatment shows an acceptable safety profile and a substantial antitumour activity in the treatment of MBC, even in elderly patients and in those with visceral disease.