Objective. To conduct a comparative assessment of the immediate efficacy and safety of endoscopic removal of superficial epithelial lesions of the colon≤25 mm in size using endoscopic mucosal resection (EMR) and underwater endoscopic mucosal resection (UEMR). Material and methods. The study included 109 patients from 5 clinical institutions who underwent removal of 149 superficial epithelial lesions of the rectum and colon. The work was prospective multicenter. Results. Both groups were comparable in all parameters from the side of patients and lesions, however, the size of lesions removed by EMR (n=72) was larger (p=0.004) than those resected by UEMR (n=77), 15 [13; 20] mm and 14 [12; 18] mm, respectively. The complication rates were similar, while direct perforation was observed only in the EMR group, with borderline significance (p=0.052). Prophylactic hemostatic therapy was prescribed significantly more often in the EMR group. The duration of removal was shorter in the UEMR group (p<0.001); 180 [120; 270] versus 240 [180; 400] sec. There were no significant differences in the rates of en bloc removal and R0 (p=0.7 and p=0.5, respectively). Conclusion. Underwater resection has a number of advantages over traditional EMR, such as: theoretical cost-effectiveness (no need to use an injector), higher speed of execution, and probably a lower risk of direct perforation. The rates of en bloc removal and R0 removal for lesions ≤25 mm do not differ. Thus, underwater resection is an effective alternative to traditional EMR for the removal of superficial epithelial lesions ≤25 mm in size. Further studies involving other patient groups and assessing long-term results are needed for subsequent clinical implementation of this technique.
606 Background: CDK4/6 inhibitors are used to treat HR+/HER2- metastatic breast cancer in combination with endocrine therapy. However, there is still a lack of evidence about combined endocrine therapy in neoadjuvant setting. VOG-01 is a phase II randomized trial that evaluated the effects of combination ribociclib plus fulvestrant and GnRH-a as neoadjuvant therapy in premenopausal patients. Methods: Premenopausal women with HR+/HER2-negative stage II-III were randomly assigned to Fulvestrant (500 mg on the 1st, 15th, 28th days of the first cycle, then once every 28 days), Triptorelin (3.75 mg every 28 days) and Ribociclib (600 mg daily, 3 weeks/4) during 16-24 weeks (NET), or Doxorubicin 60 mg/m2 + Cyclophosphamide 600 mg/m2 x4 21-day courses followed by Docetaxel 75 mg/m2 x4 21-day courses (NCT). Primary endpoint was objective response rate. Secondary endpoints were pathological response rate (RCB), frequency of breast-conserving surgery, severity of adverse events and the quality of life (EORTC QLQ-C30). Results: Eighty two patients were recruited. The objective response rate was 83% in the NET and 71% in the NCT (p = 0.2). Complete pathological response (RCB 0) was in 2 cases (5%) in the NET and in 4 cases (10%) in the NCT; RCB I was in 1 case (2.6%) in the NCT and did not occur in the NET; RCB II - 55% in the NET and 62% in the NCT, RCB III was in 40% and 26% respectively. Breast-conserving surgery were not so common in both groups: 37% in the NET and 32% in the NCT (p=0.5). Severe adverse events (CTCAE ver 5 G3-4) were 66% in the NET and 87% in NCT (p < 0.019). Quality of life significantly decreased during NCT compared with NET: the total score was 75.7±22.2, 42.0±19.7, 66.3±12.9 in NCT at visits on 1-12-24- weeks and 76.4±20, 70.7±25.4, 76.1±20.5 in NET at the same visits (p < 0.05). Conclusions: For the first time randomised trial comparing NET and NCT was conducted in premenopausal women with HR+/HER2- early breast cancer. NET was not inferior to standard NCT in terms of objective response rate, complete or pronounced pathological response rate and breast-conserving surgery. At the same time it was associated with a lower severity of adverse events and increased quality of life. Nevertheless new treatment approach requires confirmation of its effectiveness in large studies. Clinical trial information: NCT04753177 .
Studies of drugs from the group of cyclin-dependent kinase 4/6 (CDK4/6) inhibitors as first-line therapy are currently not limited to the group of patients with metastatic luminal Her2-negative (ER+/HER2-) breast cancer. A number of preclinical and clinical studies have demonstrated the potential of CDK4/6 inhibitors in the treatment of HER2-positive breast cancer with positive expression of hormone receptors («triple-positive» subtype). However, in these studies, CDK4/6 inhibitors were used together with monoclonal antibodies (Trastuzumab, Pertuzumab). This article presents a case of using a combination of an aromatase inhibitor and a CDK4/6 inhibitor without chemotherapy and monoclonal antibody (MAB) drugs as a first-line treatment for metastatic Her2-positive breast cancer in the St. Petersburg City Clinical Oncology Dispensary.
Background. Hyperglycemia (HG) is an on-target effect of ALP, and prophylactic with metformin was shown to decrease the rate and severity of HG. Here we present efficacy and safety of ALP in a large cohort of patients with rational approach to metformin usage based on risk factors of HG. Material and Methods. Patients (pts) with HR+/HeR2- PIK3CAmut ABC were treated with ALP 300 mg orally and FUL 500 mg IM until disease progression or intolerance. the primary endpoints were progression free survival (PFS) and rate of grade 3/4 HG in different risk groups. Pts were stratified to risk groups of HG based on the algorithm before starting ALP and received MET for prevention of HG. Results. a cohort comprised 139 pts. the median PFs (mPFS) on ALP – was 7.0 (CI 95 %: 5.0–8.9). the risk of HG was assessed in 138 pts: low (47), moderate (46), and high (42) risk, and 3 pts with type 2 diabetes mellitus. any grade HG was reported in 62 % pts, no cases HG G4 were detected. HG G3 was reported in 13 % pts; 10 % pts required ALP dose reduction to 250 mg due to HG G3; 3 pts (2 %) discontinued ALP due to HG. the mPFS in our analysis was longer than in BYlieve trial in cohort C: 7.0 vs 5.6 mo. We suggest that prophylactic of HG allowed maintenance of full dose of ALP in most patients and thus increased the efficacy of ALP. Furthermore, in contrast to the METALLICA trial we distinguished a low risk group (33 %) of pts who do not need the prophylactic use of MET. Conclusion. Rational use of MET in pts with moderate and high risk of HG reduces the frequency and severity of HG, decreases the rate of ALP dose reductions and as a result may increase the efficacy of ALP. Pts with low risk of HG don’t need MET for HG prevention.
Neuroendocrine tumors (NETs) include heterogeneous neoplasms that can be functional or symptomatically active (functioning) or non-functioning. The overall incidence of NETs is growing faster than the incidence of all human malignancies. NETs are the second most common gastrointestinal cancers, characterized by frequent liver metastasis, which is a major factor affecting the quality of life and significant survival of patients. Cytoreductive treatment of liver metastases (NELM) is the method of choice aimed at ensuring prolongation of patient survival and improving control of hormonal symptoms resistant to conservative therapy. Surgical resection of metastases is indicated in patients with well-differentiated (G1/G2) tumors, while its feasibility and complexity in severity dictate the degree of liver involvement. As a result of advances in surgical techniques in recent years, 1- and 2-stage or repeat liver resections are performed safely and effectively by surgeons with the treatment of NETs. The wide range of interventional radiological treatments for NELM with limitations requires reasons, which is the basis for adjunctive or alternative surgery. In general, liver-directed therapies can precede the administration of systemic molecular targeted agents and chemotherapy for patients with metastatic stage and severe liver disease, which leads to the fact that patients continue to be treated only with somatostatin analogues (SAA). Cytoreductive surgery of NETs is not limited to liver metastases, but is also used in peritoneal carcinomatosis. The large variability of clinical manifestations and the prevalence of the tumor process determine the need for an individual regimen for each patient within the framework of the MDT. In this article, we discuss the surgical approach to metastatic small bowel NETs: primary tumor, liver metastases and peritoneal carcinomatosis.
