Drainage fluid LDH and neutrophil to lymphocyte ratio as biomarkers for early detecting anastomotic leakage in patients undergoing colorectal surgery.

OBJECTIVES: In this study, we investigated the role of several circulating and drainage fluid biomarkers for detecting postoperative complications (PCs) and anastomotic leakage (AL) in patients undergoing colorectal surgery. METHODS: All consecutive patients undergoing colorectal surgery between June 2018 and April 2020 were prospectively considered. On postoperative days (POD) 1, 3, and 5, we measured lactate dehydrogenase (LDH) in drainage fluid, C-reactive protein (CRP) in serum and drainage fluid, and neutrophil to lymphocyte ratio (NLR). RESULTS: We enrolled 187 patients. POD1 patients with AL had higher serum CRP levels, while on POD3 and on POD5 higher NLR and serum CRP. LDH and CRP in drainage fluid were also significantly higher at both time points. The area under the curves (AUCs) of serum and drainage fluid CRP were 0.752 (0.629-0.875) and 0.752 (0.565-0.939), respectively. The best cut-off for serum and drainage fluid CRP was 185.23 and 76 mg/dL, respectively. The AUC of NLR on POD3 was 0.762 (0.662-0.882) with a sensitivity and specificity of 84 and 63 %, respectively, at a cut-off of 6,6. Finally, drainage fluid LDH showed the best diagnostic performance for AL, with an AUC, sensitivity, and specificity of 0.921 (0.849-0.993), 82 %, and 90 % at a cut-off of 2,186 U/L. Trends in serum parameters between patients with or without PCs or AL were also evaluated. Interestingly, we found that NLR decreased faster in patients without PCs than in patients with PCs and patients with AL. CONCLUSIONS: Drainage fluid LDH and NLR could be promising biomarkers of PCs and AL.

Neratinib as adjuvant therapy in patients with HER2 positive breast cancer: expert opinion.

Neratinib is a tyrosine kinase receptor inhibitor used in the extended adjuvant therapy of early-stage breast cancer. After adjuvant trastuzumab therapy, neratinib reduces the risk of recurrence and, if taken within 1 year from trastuzumab, significantly improves the invasive disease-free survival of patients with early-stage human epidermal growth factor receptor-2 positive (HER2+) breast cancer with no increased risk of long-term toxicity. Diarrhea, the most common adverse event associated with neratinib use, deters some clinicians from prescribing this drug. However, neratinib-related toxicity is predictable, short-lived, mostly limited to the first month of treatment and can be managed with dose-escalation and prophylactic strategies. Thus, close surveillance and prompt management, relying on supportive care and administration schedule modification, allows discontinuation of treatment to be avoided.

Utility of virtual stenting in treatment of cerebral aneurysms by flow diverter devices.

Successful endovascular treatment by stenting of intracranial aneurysms requires proper placement of the device and appropriate choice of its diameter and length. To date, several methods have been employed to achieve these goals, although each has inherent critical issues. Recently developed stent planning software applications can be used to assist interventional neuroradiologists. Based on a 3D-DSA image acquired before stenting, these applications simulate and visualize the final placement of the deployed stent. In this single-centre retrospective study, 27 patients undergoing an intravascular procedure for the treatment of intracranial aneurysms from June 2019 to July 2020 were evaluated according to strict inclusion criteria. Stent virtualization was performed with Syngo 3D Aneurysm Guidance Neuro software. We compared the software-generated stent measurement and measurements taken by the interventional radiologist. Statistical analysis was performed using the STAC web platform. Mean and standard deviations of absolute and relative discrepancies between predicted and implanted stents were recorded. Friedman's nonparametric test was used to refute the null hypotheses, i.e. (I) discrepancies between the size of virtual and implanted stents would occur, and (II) operator influence does not affect the outcome of the virtual stenting process. Based on these observations, it is believed that the virtual stenting process can validly assist interventional neuroradiologists in selecting the appropriate device and reducing peri- and post-procedural complications. The results of our study suggest that virtual reality simulation of devices used for endovascular treatment of intracranial aneurysms is a useful, rapid, and accurate tool for interventional procedure planning.

Efficacy of recanalization therapy for ischemic stroke: multicenter hospital network experience.

PURPOSE: Stroke is a leading cause of long-term disability with high mortality rate in the first year after the event. In Campania, mechanical thrombectomy treatment significantly increases in the last 3 years, as well as hospitals delivering acute stroke treatments. The aim of this study is to demonstrate how a full opening of our stroke network improves stroke management and stroked patients' survival in Campania. MATERIAL AND METHODS: In Federico II University Hospital of Naples acting as a HUB center of 7 peripheral SPOKE hospitals in regional territory, 68 patients with acute ischemic stroke were evaluated with NIHSS and m-RS clinical scores and neuroradiological ASPECT scores, from January 1 to December 31, 2021. At hospital discharge, NIHSS score and three months after m-RS score were re-assessed to evaluate the therapeutic effects. RESULTS: Forty-two of 68 patients (63%) admitted to our hub center had ischemic acute stroke at CT evaluation; 29 patients had ASPECT score > 7 (69%), and 6 a score < 7 (14%). At admission, NIHSS score mean value was 10.75, and m-RS score mean value was 0.74. At discharge, NIHSS score mean value was 7.09. After three months, m-RS score mean value was 0.74. DISCUSSION: The inter-company agreement between Federico II University and several peripheral hospitals allows an absolute and relative increase in endovascular mechanical thrombectomy and intravenous thrombolysis procedures, with a relative prevalence of mechanical thrombectomy. A regional implementation of the stroke multi-disciplinary care system is hardly needed to ensure the optimum treatment for the largest number of patients, improving patient's outcome.

Multicenter retrospective cohort Italian study on elective laparoscopic cholecystectomy performed by the surgical residents.

PURPOSE: This retrospective multicenter cohort study aimed to evaluate the clinical outcomes (mortality rate, operative time, complications) of elective laparoscopic cholecystectomy (LC) when performed by a surgical resident in comparison to experienced consultant in the backdrop of Italian academic centers. METHODS: Retrospective review of all patients undergoing elective LC between January 2016 and January 2022 at six teaching hospitals across Italy was performed. Cases were identified using the Current Procedural Terminology (CPT) code 5123 (LC without cholangiogram). All cases of emergency surgery, ASA score > 3, or when cholecystectomy was performed with another surgical procedure, were excluded. All suitable cases were divided into 2 groups based on primary surgeon: consultant or senior resident. Main outcome was complication rates (intraoperative and peri/postoperative); secondary outcomes included operative time, the length of stay, and the rate of conversion to open. RESULTS: A total of 2331 cases (1425 females) were included, of which, consultants performed 1683 LCs (72%), while the residents performed 648 (28%) surgeries. The groups were statistically comparable regarding demographics, history of previous abdominal surgery, operative time, or intraoperative complications. The rate of conversion to open cholecystectomy was 1.42% for consultant and none for resident (p = 0.02). A statistically significant difference was observed between groups regarding the average length of stay (2.2 ± 3 vs 1.6 ± 1.3 days p = 0.03). Similarly, postoperative complications (1.7% vs 0.5%) resulted in statistically significant (p = 0.02) favoring resident group. CONCLUSIONS: Our study demonstrates that in selected patients, senior residents can safely perform LC when supervised by senior staff surgeons.

Extended Adjuvant Endocrine Treatment in Luminal Breast Cancers in the Era of Genomic Tests.

In patients with early-stage endocrine receptor-positive (ER+) breast cancer (BC), adjuvant endocrine therapy (ET) for 5 years is the standard of care. However, for some patients, the risk of recurrence remain high for up to 15 years after diagnosis and extended ET beyond 5 years may be a reasonable option. Nevertheless, this strategy significantly increases the occurrence of side effects. Here we summarize the available evidence from randomized clinical trials on the efficacy and safety profile of extended ET and discuss available clinical and genomic tools helpful to select eligible patients in daily clinical practice.

Luteinised unruptured follicle syndrome: pathophysiological background and new target therapy in assisted reproductive treatments.

Luteinised unruptured follicle syndrome (LUFS) is a cause of infertility consisting in the unruptured of the dominant follicle after the LH-surge. In fact, during assisted reproductive treatments (ART) clomiphene citrate and letrozole are frequently administered in order to achieve ovulation. However, considering the pathophysiology of LUFS, new possible therapy can be proposed. On this scenario, we performed a review of the literature searching for LUFS recurrency and its impact in infertility and ART. An inflammation theory has been proposed that can be fuel for further therapeutic possibilities. In particular, considering the increase in granulocytes accumulation, the granulocyte colony-stimulating factor (G-CSF) administration has been proposed as target therapy in IUI cycles hampered by LUFS. Although data are encouraging, randomised controlled trials are needed in order to confirm the efficacy of G-CSF administration for LUFS patients.

Feasibility and Safety of Laparoscopic Complete Mesocolic Excision (CME) for Right-sided Colon Cancer: Short-term Outcomes. A Randomized Clinical Study.

OBJECTIVE: The aim of this prospective clinical study is to compare short-term outcome of laparoscopic right hemicolectomy using the Complete Mesocolic Excision (CME group) with patients who underwent conventional right-sided colonic resection (NCME group). SUMMARY BACKGROUND DATA: Although CME with central vascular ligation in laparoscopic right hemicolectomy is associated with a significant decrease in local recurrence rates and improvements in cancer-related 5-year survival, there may be additional risks associated with this technique because of increased surgical complications. As a result, there is controversy surrounding its use. METHODS: In this randomized controlled trial, several primary endpoints (operative time, intraoperative blood loss, other complications, conversion rate, and anastomotic leak) and secondary endpoints (overall postoperative complications) were evaluated. In addition, we evaluated histopathologic data, including specimen length and the number of lymph nodes harvested, as objective signs of the quality of CME, related to oncological outcomes. RESULTS: The CME group had a significantly longer mean operative time than the NCME group (216.3 minutes vs 191.5 minutes, P = 0.005). However, the CME group had a higher number of lymph nodes (23.8 vs 16.6; P < 0.001) and larger surgical specimens (34.3 cm vs 29.3 cm; P = 0.002). No differences were reported with respect to intraoperative blood loss, conversion rate, leakage, or other postoperative complications. CONCLUSIONS: In this study laparoscopic CME were a safe and feasible technique with improvement in lymph nodes harvesting and length of surgical specimens with no increase of surgical intraoperative and postoperative complications.

Post-Progression Treatments after Palbociclib plus Endocrine Therapy in HR+/HER2- Metastatic Breast Cancer Patients: What Is the Better Choice?

BACKGROUND: To date, a consensus has not yet been reached about the therapy sequence after disease progression (PD) on CDK4/6 inhibitors in patients with HR+/HER2- metastatic breast cancer (MBC). OBJECTIVES: The present study assesses, in a real-world setting, the activity of different subsequent therapies in patients who experienced a PD on palbociclib (P) + endocrine therapy (ET), to evaluate the best therapy sequence. METHODS: This is a multicenter retrospective observational study. Records of consecutive HR+/HER2- MBC patients from January 2017 to May 2019 were reviewed. The primary endpoint was the evaluation of progression-free survival (PFS) according to subsequent treatment lines after progression on P+ET. Toxicity data were also collected. RESULTS: The outcomes were analyzed in 89 MBC patients that had progressed on previous P+ET: 17 patients were on hormone therapy (HT) and 31 patients on chemotherapy (CT) as second-line treatments; seven patients were on HT and 34 on CT as third-line therapies. PFS of patients treated with HT as second-line therapy is significantly improved when compared with patients treated with CT (p=0.01). Considering third-line settings, the difference in PFS was not statistically different between HT and CT. A better outcome in terms of toxicity is observed among HT patients for both second- and third-line therapies. CONCLUSIONS: patients who were progressive on P+ET could still benefit from a subsequent ET. In patients who experienced a good efficacy from prior ET, without visceral metastatic sites, HT seems the most suitable option, when compared to CT, also in terms of safety.

Enhanced angiogenesis in the 3D dynamic responsive implant for inguinal hernia repair ProFlor.

Biologic response to hernia prostheses represents a continuous source of debate. Conventional hernia meshes, in their typical static, passive configuration have been used for decades to reinforce the herniated abdominal wall. These flat implants, mainly fixated with sutures or tacks, induce poor quality fibrotic ingrowth that shrinks the mesh. In groin hernia repair, flat meshes are applied in the delicate inguinal surrounding where uncontrolled development of a scar plate can impair movement and may incorporate the sensitive nerves crossing this area. Complications deriving from mesh fixation and nerve entrapment are frequent and unpleasant for patients. To remedy these problems, a multilamellar shaped 3D device with a dynamic responsive behavior has recently been developed to repair inguinal hernia. Its inherent dynamic compliance during inguinal movements has shown to induce enhanced biological response with ingrowth of newly formed connective tissue, muscle fibers, and nerves. The function of these highly specialized tissue structures is supported by the contextual development of newly formed arteries and veins. The scope of the study was to assess quantity and quality of vessels, which had ingrown in the 3D hernia device in the short-term, medium-term, and long-term post-implantation, in biopsy specimens gathered from inguinal hernia patients operated with the 3D device. Starting from an early stage, widespread angiogenesis was evident within the 3D structure. Arteries and veins increased in quantity showing progressive development until full maturation of all specific vascular components throughout the mid-term, to long-term, post-implantation. High quality biologic ingrowth in hernia prosthetics needs an adequate vascular support. The broad network of mature arteries and veins evidenced herewith seems to confirm the enhanced biological features of the dynamic responsive 3D device whose features resemble a regenerative scaffold, an ideal feature for the treatment of the degenerative source of inguinal hernia disease.

FOXP1 circular RNA sustains mesenchymal stem cell identity via microRNA inhibition.

Stem cell identity and plasticity are controlled by master regulatory genes and complex circuits also involving non-coding RNAs. Circular RNAs (circRNAs) are a class of RNAs generated from protein-coding genes by backsplicing, resulting in stable RNA structures devoid of free 5' and 3' ends. Little is known of the mechanisms of action of circRNAs, let alone in stem cell biology. In this study, for the first time, we determined that a circRNA controls mesenchymal stem cell (MSC) identity and differentiation. High-throughput MSC expression profiling from different tissues revealed a large number of expressed circRNAs. Among those, circFOXP1 was enriched in MSCs compared to differentiated mesodermal derivatives. Silencing of circFOXP1 dramatically impaired MSC differentiation in culture and in vivo. Furthermore, we demonstrated a direct interaction between circFOXP1 and miR-17-3p/miR-127-5p, which results in the modulation of non-canonical Wnt and EGFR pathways. Finally, we addressed the interplay between canonical and non-canonical Wnt pathways. Reprogramming to pluripotency of MSCs reduced circFOXP1 and non-canonical Wnt, whereas canonical Wnt was boosted. The opposing effect was observed during generation of MSCs from human pluripotent stem cells. Our results provide unprecedented evidence for a regulatory role for circFOXP1 as a gatekeeper of pivotal stem cell molecular networks.

Inguinal Hernia: Defect Obliteration with the 3D Dynamic Regenerative Scaffold Proflor™.

Prosthetic inguinal hernia repair presents significant challenges. Some of these, such as mesh fixation and quality of the biologic response, are still debated among surgeons. For example, there is no strong consensus regarding a specific condition that characterizes the surgical procedure during herniorrhaphy. This issue concerns management of the hernia defect, which in conventional hernia repair with flat meshes remains patent. However, a critical analysis of typical postoperative complications after inguinal hernia repair reveals that some of these adverse events are related to patency of the hernial opening. Postoperative discomfort, pain with specific movements and even hernia recurrence can be caused by incomplete or defective management of the hernia defect. For this reason, a deeper understanding of this topic would be useful for improving postoperative outcomes. A recently updated concept for inguinal hernia repair takes this technical aspect into consideration. It is based on the use of a newly developed 3D scaffold-ProFlor™ (Insightra Medical, Inc., Clarksville, TN, USA)-that is intended to be deployed into the defect. This novel hernia repair device has interesting and original features, such as dynamic responsivity in compliance with inguinal movement, fixation-free mode and regenerative behavior that counteracts the degenerative effects of the disease. Another additional proprietary feature of this 3D scaffold is the full and permanent obliteration of the defect, which is a crucial aspect to improve outcomes by avoiding the typical adverse effects of this surgical procedure. Obliteration of the hernia defect with the 3D dynamic regenerative scaffold ProFlor™ appears to be superior to coverage by means of static (passive) flat meshes/plugs used in conventional hernia repair. This report highlights the principles of this procedural approach.

Metabolic syndrome and early stage breast cancer outcome: results from a prospective observational study.

PURPOSE: Obesity and insulin resistance have been associated with poor prognosis in breast cancer (BC). The present prospective study aimed to investigate the impact of metabolic syndrome (MetS) and its components on early BC (eBC) patients' outcome. METHODS: MetS was defined by the presence of 3 to 5 of the following components: waist circumference > 88 cm, blood pressure ≥ 130/≥ 85 mmHg, serum levels of triglycerides ≥ 150 mg/dL, high density lipoprotein < 50 mg/dL and fasting glucose ≥ 110 mg/dL. Seven hundred and seventeen patients with data on ≥ 4 MetS components at BC diagnosis were enrolled. Study population was divided into two groups: patients with < 3 (non-MetS) vs. ≥ 3 components (MetS). Categorical variables were analyzed by Chi-square test and survival data by log-rank test and Cox proportional hazards regression model. RESULTS: Overall, 544 (75.9%) and 173 (24.1%) women were categorized as non-MetS and MetS, respectively. MetS patients were more likely to be older, postmenopausal, and insulin-resistant compared to non-MetS patients (p < 0.05). In multivariate analysis, MetS patients had a numerically higher risk of relapse [disease-free survival (DFS), hazard ratio (HR) 1.51, p = 0.07] and a significantly higher risk of death compared to non-MetS patients [overall survival (OS), HR 3.01, p < 0.0001; breast cancer-specific survival (BCSS), HR 3.16, p = 0.001]. Additionally, patients with 1 to 2 components of MetS had an increased risk of dying compared to patients with 0 components (OS, HR 4.90, p = 0.01; BCSS, HR 6.07, p = 0.02). CONCLUSIONS: MetS correlated with poor outcome in eBC patients. Among patients without full criteria for MetS diagnosis, the presence of 1 or 2 components of the syndrome may predict for worse survival.

Innate Immunity Effector Cells as Inflammatory Drivers of Cardiac Fibrosis.

Despite relevant advances made in therapies for cardiovascular diseases (CVDs), they still represent the first cause of death worldwide. Cardiac fibrosis and excessive extracellular matrix (ECM) remodeling are common end-organ features in diseased hearts, leading to tissue stiffness, impaired myocardial functional, and progression to heart failure. Although fibrosis has been largely recognized to accompany and complicate various CVDs, events and mechanisms driving and governing fibrosis are still not entirely elucidated, and clinical interventions targeting cardiac fibrosis are not yet available. Immune cell types, both from innate and adaptive immunity, are involved not just in the classical response to pathogens, but they take an active part in "sterile" inflammation, in response to ischemia and other forms of injury. In this context, different cell types infiltrate the injured heart and release distinct pro-inflammatory cytokines that initiate the fibrotic response by triggering myofibroblast activation. The complex interplay between immune cells, fibroblasts, and other non-immune/host-derived cells is now considered as the major driving force of cardiac fibrosis. Here, we review and discuss the contribution of inflammatory cells of innate immunity, including neutrophils, macrophages, natural killer cells, eosinophils and mast cells, in modulating the myocardial microenvironment, by orchestrating the fibrogenic process in response to tissue injury. A better understanding of the time frame, sequences of events during immune cells infiltration, and their action in the injured inflammatory heart environment, may provide a rationale to design new and more efficacious therapeutic interventions to reduce cardiac fibrosis.

Laparoscopic adrenalectomy: preoperative data, surgical technique and clinical outcomes.

BACKGROUND: laparoscopic adrenalectomy has become the standard treatment for adrenal lesions. The better clinical outcoms of laparoscopic technique are valid for treatment of small benign masses (< 5-6 cm), instead there are still open questions in literature regarding the correct management of larger lesions (> 6 cm) or in case of potentially malignant adrenal tumors. The aim of this study is to evaluate the outcomes of laparoscopic adrenalectomy in a referral surgical department for endocrine surgery. METHODS: at the University Hospital Policlinico "P. Giaccone" of Palermo between January 2010 and December 2017 we performed a total of 81 laparoscopic adrenalectomy. We created a retrospective database with analysis of patients data, morphologic and hormonal characteristics of adrenal lesions, surgical procedures and postoperative results with histological diagnosis and complications. RESULTS: Mean size of adrenal neoplasm was 7,5 cm (range 1.5 to 18 cm). The mean operative time was 145 min (range 75-240). In statistical analysis lenght of surgery was correlated to the lesion diameter (p < 0.05) but not with pre-operative features or histological results. 5 intraoperative complications occurred. Among these patients 4 presented bleeding and 1 a diaphagmatic lesion. No conversion to open surgery was necessary and no intraoperative blood transfusion were required. Mean estimated blood loss was 95 ml (range 50-350). There was no capsular disruption during adrenal dissection. Mean length of hospital stay was 3.7 days (range 3-6 days). CONCLUSIONS: Laparoscopic adrenalectomy is a safe procedure with low rate of morbidity. An accurate preoperative radiological examination is fundamental to obtain a stringent patients selection. The lesion diameter is related to longer operative time and appeares as the main predictive parameter of intraoperative complications but these results are not statistically significant. On the other side secreting adrenal tumors require more attention in operative management without increased rate of postoperative complications.

Metabolic and anthropometric changes in early breast cancer patients receiving adjuvant therapy.

Weight gain and metabolic changes have been related to survival of early breast cancer patients (EBC). ''However, factors influencing metabolism post-diagnosis are not fully understood. We measured anthropometric [body mass index (BMI), body weight, waist and hip circumferences, and waist-to-hip ratio] and metabolic (levels of insulin, glucose, H1Ac, total, HDL, and LDL cholesterol, triglycerides, and the homeostasis model assessment score [HOMA]) parameters in 433 pre- and post-menopausal women with EBC at diagnosis and 3, 6, 9, 12, and 24 months thereafter. At diagnosis, compared with post-menopausal women, pre-menopausal patients were more likely to be leaner and to have a lower BMI, smaller waist and hip circumferences, and waist-to-hip ratio. They had also lower glucose, HbA1c, and triglyceride levels and a lower HOMA score. Furthermore, they were more likely to have an estrogen- and/or progesterone-positive tumor and a higher proliferating breast cancer. During the first two post-diagnosis years, all women showed a significant increase of weight (+0.72 kg/year, P < 0.001), waist circumference (+1.53 cm/year, P < 0.001), and plasma levels of LDL cholesterol (+5.4 mg/dl per year, P = 0.045) and triglycerides (+10.73 mg/dl per year, P = 0.017). In patients receiving chemotherapy only, there was a significant increase in hip circumference (+3.16 cm/year, P < 0.001) and plasma cholesterol levels (+21.26 mg/dl per year, P < 0.001). We showed that weight, body fat distribution, and lipid profile changed in EBC patients receiving adjuvant therapy. These changes occurred during the first 2 years after diagnosis and were not specifically related to chemotherapy, menopausal status, or initial body weight.

Multiple Ipsilateral Inguinal Hernias: More Frequent Than Imagined, If Undetected Source of Discomfort, Pain, and Re-interventions.

The article reports the incidence of multiple inguinal protrusions in the same groin in a patient collect who underwent open hernia repair. Multiple ipsilateral inguinal hernias compose an almost neglected topic that, if not identified during hernia repair, could lead to unclear discomfort, pain, and reoperation. A collect of 100 consecutive open anterior inguinal hernia procedures was analyzed. The patients were divided into two subsets-A: patients with a single protrusion and B: patients with more than one protrusion simultaneously arising from the inguinal floor. The single hernias from cohort A and the multiple hernias from cohort B were further categorized using the Nyhus classification system. Eighty-eight single unilateral hernias were detected and 12 multiple inguinal hernias were ipsilaterally arising from the same groin. Nine percent of the multiple protrusions were double (three double indirect and six in combination direct + indirect). Three patients (3%) presented with triple protrusions; of those two individuals, one had a combination of double indirect, one had a direct hernia, and the third patient showed a tricomponent protrusion (hernia of the fossa supravescicalis + hernia of the fossa inguinalis media + indirect hernia). These numbers demonstrate that multiple ipsilateral inguinal hernias are more frequent than imagined. If undiscovered during a herniorrhaphy, the "forgotten" protrusion may generate unclear groin pain requiring reoperation. Consequently, is to envisage that many re-interventions will likely involve false "recurrences." Therefore, during hernia repair, more attention and adhesiolysis is essential during inspection of the inguinal floor. In fact, a careful exposure of the anatomical structures of the groin could be very advantageous in properly managing such conditions. This kind of surgical approach can help to prevent patient's discomfort and re-interventions.

Sacituzumab Govitecan for the treatment of advanced triple negative breast cancer patients: a multi-center real-world analysis.

Objective: The objective of this multicenter, observational, retrospective analysis was to evaluate the safety and efficacy of sacituzumab govitecan in metastatic triple-negative breast cancer (mTNBC) patients managed according to common clinical practice in Italy. Methods: Data were retrieved by 7 sites. Triple-negative BC was defined by the lack of expression of estrogen receptor (ER <1%), progesterone receptor (PgR <1%) and human-epidermal growth factor receptor-2 (HER2 0, 1+, 2+ ISH-not amplified) according to standard ASCO-CAP criteria. Demographic and clinical characteristics were collected. Premedication, dose modifications and treatment schedule were based on the approved label of the product. Adverse events (AEs) were assessed according to NCI-CTCAE v5.0. Results: Fifty-seven eligible patients who received sacituzumab govitecan for mTNBC were included. Median age was 53 years (range 25-75). Approximately 70% of patients had an initial diagnosis of TNBC. Median time from the diagnosis of metastatic BC to start of sacituzumab govitecan was 17 months (range 0-97) and median number of previous therapies was 3 (range 1-7). The most common sites of metastasis were lymph nodes (63.1% of patients), lung (57.9%), bone (50.8%) and liver (38.6%). Eight (14.0%) patients had a disease-free interval ≤12 months. A total of 32 (56.1%) deaths were observed and the median overall survival (OS) was 12.43 months (95% CI, 7.97 months-not reached). At a median follow-up of 10.6 months, 45 patients (78.9%) had progression and the median progression-free survival (PFS) was 4.9 months (95% CI, 3.7-7.1 months). Partial tumour response was observed in 19 patients (33.3%), stable disease in 16 (28.1%) and disease progression in 22 patients (38.6%). The most common treatment-related AEs were anemia (66.6% of patients), alopecia (66.6%), neutropenia (59.6%), nausea (42.1%) and diarrhea (38.6%). Neutropenia was the most common serious treatment-related AE: 21.0% and 8.7% of patients experienced grade 3 or 4 neutropenia, respectively. Twenty-two patients (38.6%) reduced the dose and 5.3% permanently discontinued treatment. Conclusion: The results of this real-world analysis showed that both safety and efficacy of sacituzumab govitecan in mTNBC patients are consistent with that previously reported in regulatory trials. The use of premedication and supportive measures was associated with a satisfactory toxicity profile.