Vol 29, No 7 (2022)

Stem cell mobilization is the necessary part of high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation. The primary goal of mobilization is a sufficient CD34 cell dose collection. Mobilization efficacy determines choice of subsequent treatment. Approach to stem cell collection depends on clinical case and previous mobilization outcomes. So, mobilization failure could be a major problem. The combination of plerixafor and G-CSF significantly increases stem cell yield, but high cost of plerixafor limits its clinical use. Chemomobilization is also an effective mobilization strategy. Evaluating its advantages and disadvantages, optimal chemomobilization regimen may be a possible way to collect target stem cell yield. In this review general approaches to the CD34+ cell mobilization, risk factors associated with poor mobilization and its prevention, efficacy data of chemomobilization with cytarabine and etoposide are discussed.

Currently, there are no reliable strategies for personalizing the treatment of patients with early-stage triple-negative breast cancer (TNBC). The advent of immune checkpoint inhibitors in modern oncology has significantly improved survival in some cancers. New evidence suggests that tumor-infiltrating lymphocytes (TILs) are associated with response to both chemotherapy and immunotherapy in patients with TNBC. Why hasn’t such a simple and cheap biomarker as TILs entered into routine practice? There are still problems to be solved.

Bladder cancer (BC) is one of the most common malignant neoplasms in urology. Recently, approaches to the treatment of muscle-invasive bladder cancer have undergone significant changes: from radical cystectomy to combined treatment with bladder sparing; from open surgery to endoscopic minimally invasive surgery and robot-assisted surgery. This article provides an overview of modern methods of treatment of muscle-invasive bladder cancer.

Background. Cushing’s disease (CD) is a severe neuroendocrine pathology caused by adrenocorticotropic hormone (ACTH) hypersecretion by a pituitary tumor. Modern methods of treating CD include neurosurgical intervention, radiation and drug therapy. Drug therapy is an alternative treatment option for persistent or relapsing disease. With CD, the most pathogenetically justified drugs that act on corticotropinoma are somatostatin analogues (pasireotide) and D2-dopamine receptor agonists (cabergoline). Combination therapy is a valuable and understudied treatment option for CD. Objective. Improvement and optimization of the tactics of choosing drug therapy for patients with persistent or recurrent CD. Methods. The work was performed according to the design of an interventional study. The study involved 51 patients with confirmed CD in the active stage of persistent and relapsing course, with indications for the appointment of drug therapy with drugs of the central type of action. By random number method, all patients were divided into 3 comparable groups of 18, 18 and 15 persons, respectively. The first group was prescribed pasireotide (1.2 mg/day), the second - cabergoline (2.0 mg per week), the third - their combination (0.6 mg/day and 1.0 mg per week). The patients were followed-up for 6 months. Assessment of laboratory and instrumental indicators of the activity of endogenous hypercortisolism, as well as the presence of adverse events, was carried out at the beginning of the study and 6 months after the start of therapy. Results. Statistically significant results of therapy efficacy were obtained in the pasireotide monotherapy group in terms of the dynamics of a decrease in the salivary cortisol at 23:00 (P=0.004), blood cortisol (P=0.03) and ACTH (P=0.03) levels. When assessing the decrease in the urinary free cortisol (UFC) level, there was no significant difference in this group (P=0.07). There was a statistically significant decrease in the levels of UFC (P=0.03) and salivary cortisol at 23:00 (p=0.05) in the combination therapy group without a significant decrease in ACTH (p=0.325) and blood cortisol (p=0.135) levels. In the cabergoline group, there was no significant decrease in the ACTH (p=0.468), blood cortisol (p=0.367) and urine cortisol (p=0.226) levels. Normalization of the UFC level in the pasireotide group reached 30%, in the cabergoline group - 22%, in combination therapy - 67% of patients. When assessing adverse events, statistically significant differences were noted in the occurrence of newly diagnosed diabetes mellitus (P=0.0007), hyperglycemia (P=0.0000001), cholelithiasis (P=0.004), bradycardia (P=0.001) in the pasireotide group. Orthostatic hypotension (P=0.003) was more common in the cabergoline group. In the combination therapy group, diabetes mellitus (P=0.003) and hyperglycemia (P=0.000002) occurred statistically significantly more frequently. Gallstone disease (GSD) occurred more frequently in the pasireotide group (44.44%; 8) compared with cabergoline group (0.00% 0; P=0.009); in the combination therapy group, GSD occurred in 26.67% (4) of patients and did not reach statistical significance compared to cabergoline group (p=0.07). Conclusion. When analyzing the effectiveness of various options for drug therapy in patients with CD, the advantage of using somatostatin analogues both in the form of monotherapy and combination therapy was demonstrated. The rationality of prescribing combination therapy was confirmed due to comparable efficacy with greater safety in the treatment of CD with an extension of the terms of use.

Background. The thymus is a lymphoid organ where mature and naive T-lymphocytes are synthesized. A number of factors (age, stress, toxic effects, including chemotherapy, radiation therapy, surgery, hormone therapy, etc.) can lead to a violation of its structure and functional activity in cancer patients. This manifests itself in the form of hyperplasia, which can be interpreted as a residual tumor, or a recurrence of the disease. Due to the plasticity of the thymus, this process is reversible. Objective. Evaluation of the role of PET/CT in the diagnosis of thymic hyperplasia after drug therapy for lymphomas. Methods. We performed a retrospective analysis of the results of PET/CT with 18F-fluorodeoxyglucose in 103 patients with stage II-III Hodgkin’s lymphoma and non-Hodgkin’s lymphoma after drug treatment for 2018-2020. PET/CT scanning was performed on an Optima PET/CT 560 (GE) tomograph at various stages of treatment and follow-up. Results. Thymus hyperplasia was detected in 10 patients (9.7%) in the age group from 26 to 56 years, the median was 35.7 years. The vast majority of patients were under the age of 40 years - 8/80%, among them 9 women and 1 man. Hodgkin’s lymphoma was observed in 7 patients, non-Hodgkin’s lymphoma - in 3 cases. Patients underwent polychemotherapy according to BEACOPP schemes for Hodgkin’s lymphoma or R-CHOP immunochemotherapy for non-Hodgkin’s lymphomas. Thymus hyperplasia was detected, according to PET/CT data, 5-12 months (on average 8.4 months) after complete clinical and metabolic remission. The maximum standardized uptake value SUVmax ranged from 1.98 to 3.28; median - 2.52. Patients were followed-up for an average of 26 months, with no signs of recurrence of the disease. Conclusion. Thymus hyperplasia after effective drug therapy in patients with lymphomas was observed in 9.7% of cases. It was characterized by the appearance of a volumetric formation in the anterior superior mediastinum, which had a triangular shape, the apex facing the sternum, a heterogeneous or soft tissue structure with fixation of 18F-fluorodeoxyglucose. The median SUVmax was 2.52. Hyperplasia developed after an average of 8.4 months after completion of therapy. PET/CTis considered the method of choice for the differential diagnosis of thymus hyperplasia and the exclusion of the progression of the tumor process.

Background. The increase in the incidence of neuroendocrine neoplasms creates the need for an active search for factors that determine both the prognosis of the disease and the effectiveness of antitumor treatment. Markers of chronic systemic inflammation are a predisposing factor for many features of malignancy, including neuroendocrine tumors. Thus, the determination of inflammatory biomarkers is highly relevant. Objective. Evaluation of the prognostic role of the neutrophil to lymphocyte ratio (NLR), derived neutrophil to lymphocyte ratio (dNLR), platelet to lymphocyte ratio (PLR) and lymphocyte to monocyte ratio (LMR), the effect of the above factors on progression-free survival (PFS) and overall survival rate in patients with gastrointestinal neuroendocrine tumors (GINET) who received treatment at the City Clinical Oncological Dispensary from 2015 to 2020 (NET Register). Methods. The analysis of data of 69 patients with I-IV stage GINET was carried out. All patients received treatment according to standard protocols from 2015 to 2020. The demographic data of all patients, their baseline levels of leukocytes, neutrophils, lymphocytes, monocytes and platelets were analyzed. Results. The relative number of peripheral blood lymphocytes at the stage of initial assessment was the only independent factor influencing the PFS of patients: relative number of lymphocytes ŒŒŒŒ≤30% significantly increased the risk of disease progression (RR=0.97, 95% CI: 0.94-0.99; P=0.0344). Conclusion. The results obtained indicate the possibility of using indicators characterizing systemic inflammation to predict the course of GINET.

Background. Due to the achievements of modern medicine, the survival rate of patients after complex therapy of malignant brain tumors, including medulloblastoma, the most common solid malignant tumor of childhood, has significantly increased in recent years. Description of the clinical case. Patient Z., 21 years old. Medulloblastoma was diagnosed at 6 years of age. Surgical removal of the tumor, radiation and polychemotherapy were performed. After polychemotherapy, sensorineural hearing loss developed. In the Clinic of Endocrinology of the Sechenov University, the patient was diagnosed with multiple endocrine disorders. Somatotropic insufficiency was confirmed by the results of the test with glucagon: growth hormone <0.05 ng/ml at all points of the study; hypocorticism was excluded during the test with 1-24 ACTH (initial cortisol - 521 nmol/l [119-618], stimulated cortisol - 1200 nmol/l [119-618]); patient was diagnosed with type 2 diabetes mellitus: HbA1c - 7.4%, glycemia 16.9 mmol/l, negative antibodies specific for autoimmune diabetes mellitus (to pancreatic в-cells, insulin, glutamate decarboxylase, tyrosine phosphatase); preserved reserve of pancreatic в-cells. Thyroid ultrasonography and subsequent fine needle aspiration biopsy revealed left and right lobe nodules suspicious of papillary cancer (Bethesda V). Postoperative histological examination revealed papillary and follicular thyroid cancers. Data for postoperative hypoparathyroidism was not obtained, levothyroxine was prescribed in a suppressive dose. The patient continues follow-up at the endocrinology clinic. Conclusion. Considering the prevalence of endocrine and metabolic disorders after complex treatment of malignant brain tumors, timely detection of pathology and compensation of endocrine consequences is necessary.