MD-Onco

Chemotherapy-associated nausea and vomiting remain one of the most significant problems in oncology despite development of modern antiemetics. These symptoms decrease patients’ quality of life and treatment compliance and can lead to clinically significant complications including dehydration, electrolyte imbalances, and modification of antitumor therapy.

Pathogenesis of chemotherapy-associated nausea and vomiting is multifactorial and includes activation of both peripheral and central mechanisms, with key being serotoninergic and neuroendocrine NK₁ receptors. This underlies the necessity of using combination antiemetic therapy directed at various parts of vomiting reflex pathogenesis. Modern clinical guidelines make provisions for multicomponent schemes, but their efficacy is limited by low patient adherence and development of adverse effects.

Netupitant and palonosetron combination (NEPA) is a mixture of NK₁ receptor antagonist and 5-HT₃ receptor antagonist which affect the key mechanisms of chemotherapy-associated nausea and vomiting. Pharmacokinetic characteristics of the components allow to use the drug once prior to administration of chemotherapy in combination with dexamethasone which makes therapy more comfortable and increase patients’ compliance.

According to randomized clinical trials, NEPA demonstrates high efficacy in prevention of both acute and delayed chemotherapy-associated nausea and vomiting during moderately and highly emetogenic chemotherapies leading to high rates of complete remission and similar or more favorable safety profile compared to the standard of care. Additional benefits include lower need for salvage therapy and potentially lower treatment costs.

Therefore, the use of NEPA combination is a justified and effective approach to prevention of chemotherapy-associated nausea and vomiting and allows to optimize antiemetic therapy through increased efficacy, safety and treatment adherence.

Background. Sentinel lymph node biopsy (SLNB) is the standard of regional staging in early-stage breast cancer (BC). However, contemporary randomized trials (SOUND, INSEMA, NAUTILUS) demonstrate the feasibility of safe axillary surgical de-escalation in a defined subset of patients with clinically node-negative (cN0) disease. Given the low rate of axillary lymph node metastases and the limited sensitivity of SLNB, this procedure may represent overtreatment in a proportion of patients.

Aim. To evaluate the oncological safety and clinical impact of SLNB omission in patients with early-stage breast cancer and clinically intact axillary lymph nodes, and to define approaches to adjuvant therapy optimization in this cohort.

Materials and methods. A prospective randomized non-inferiority trial is being conducted at the P.A. Herzen Moscow Oncology Research Institute. Patients with early-stage BC (cTis–cT2, cN0) were randomized 1:1 to SLNB or SLNB omission. In patients with cT1c–T2 disease, intraoperative fine-needle aspiration biopsy of the sentinel lymph node was additionally performed using a fan-shaped technique. The primary endpoint is disease-free survival. Secondary endpoints include overall survival, distant metastasis-free survival, locoregional and axillary recurrence rates, and quality-of-life characteristics.

Results. The preliminary analysis included 151 patients. In the cT1a–b cohort assigned to SLNB omission, no lymph node metastases were identified. In the SLNB control group, metastases were detected in 12.5 % of patients, with involvement limited to no more than one lymph node in all cases. In the cT1c–T2 cohort, the metastatic involvement rate was 16.5 %. Intraoperative fine-needle aspiration biopsy of the sentinel lymph node demonstrated a sensitivity of 57.1 %, specificity of 100 %, positive predictive value of 100 %, and negative predictive value of 92.8 %. Favorable biological subtypes (luminal tumors) and low-to-intermediate histological grades predominated in the study population.

Conclusion. Preliminary findings suggest potential oncological safety of SLNB omission in carefully selected patients with early-stage breast cancer and cN0 status. Rigorous preoperative axillary assessment using imaging modalities is a prerequisite. Further patient recruitment and extended follow-up are required to enable definitive evaluation of long-term oncological outcomes and to refine criteria for axillary surgical de-escalation.

Background. Acute lymphoblastic leukemia (ALL) is the most common malignant neoplasm in children. Modern treatment protocols have achieved high survival rates, increasing the significance of investigating early and late therapy-related complications, including endocrine disorders. Dysfunction of the hypothalamic-pituitary axis may develop both during antitumor therapy and prior to its initiation; however, data on the dynamics of pituitary hormone levels in adolescents with ALL remain limited.

Aim. To assess blood levels of pituitary hormones – including luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin, growth hormone (GH), adrenocorticotropic hormone (ACTH), and thyroid-stimulating hormone (TSH) – in adolescents with ALL before treatment initiation and after completion of therapy.

Materials and methods. The study included 40 adolescents of both sexes with ALL (median age 14.55 (11–17) years). The control group consisted of 40 age- and sex-matched apparently healthy children (median age 15.25 (11–17) years). Pituitary hormone levels (LH, FSH, prolactin, GH, ACTH, and TSH) were measured in blood samples before treatment and after the third consolidation phase using standard radioimmunoassay and enzyme-linked immunosorbent assay kits. Mean hormone levels obtained from the control group were used as reference values. Statistical analysis was performed using Statistica 10 software.

Results. In girls before treatment, the levels of LH, FSH, and TSH, as well as the LH/FSH ratio, were within the reference range (p > 0.05). Prolactin level was elevated 2.9-fold (p < 0.05), whereas GH and ACTH levels were reduced 2.5- and 1.8-fold, respectively (p < 0.05). After the third consolidation phase, LH and FSH levels increased relative to both the baseline and reference values: LH by factors of 2.1 and 1.6, and FSH by factors of 2.3 and 2.2, respectively (p < 0.05). The LH/FSH ratio remained within the reference range. Prolactin level remained elevated, exceeding the reference range by a factor of 2.0 (p < 0.05). GH level increased 1.5-fold compared to the baseline (p < 0.05) but remained 1.6-fold lower than the reference range (p < 0.05). ACTH levels increased 2.1-fold (p < 0.05) and reached the reference values. TSH levels remained within the reference range.

In boys, LH levels were reduced 1.5-fold before treatment (p < 0.05), while FSH levels and the LH/FSH ratio were within the reference range. Prolactin level was elevated 1.8-fold (p < 0.05), and GH level was elevated 3.0-fold (p < 0.05). ACTH and TSH levels showed 1.7-fold decrease each (p < 0.05). After the third consolidation phase, LH levels normalized, increasing 1.6-fold (p < 0.05). FSH level increased 1.8-fold relative to the baseline (p < 0.05) and remained within the reference range. The LH/FSH ratio remained normal. Prolactin level increased 1.6-fold compared to the baseline (p < 0.05) and exceeded the reference range by a factor of 2.9 (p < 0.05). GH level decreased 4.3-fold relative to the baseline (p < 0.05) and was 1.4-fold below the reference values (p < 0.05). ACTH and TSH levels increased by factors of 2.2 and 1.8, respectively (p < 0.05), reaching the reference values.

Conclusion. ALL in adolescents is associated with dysfunction of the adenohypophysis and an imbalance of tropic hormones, with the direction and magnitude of changes depending on sex and treatment stage. Antitumor therapy rarely results in complete normalization of pituitary hormone levels, which is attributable to both the disease itself and the cytotoxic effects of treatment. These findings support the need for dynamic monitoring of LH, FSH, prolactin, GH, ACTH, and TSH levels in adolescents with ALL at all stages of therapy for early detection and timely correction of endocrine disorders.

Meningiomas are the most common primary intracranial tumors in adults, accounting for over 35 % of all intracranial tumors. Moreover, meningiomas occurring in children account for only 0.64 % of all meningiomas, and among intracranial tumors in children, meningiomas account for 1.42–5.00 % of cases. Because the risk of developing meningioma increases significantly with age, the proportion of healthcare costs associated with meningiomas in developed countries will continue to increase as the demographics shift toward an aging population. Compared to malignant glial tumors, meningiomas have been relatively poorly studied in terms of etiologic risk factors. Meningiomas can also be part of hereditary diseases. These tumors are primarily benign and can be observed, but the preferred treatment method is complete tumor resection, which provides good results.

According to the World Health Organization, 5-year survival rate for grade I meningioma is over 80 %. Meningiomas with a heterogeneous morphological picture or located in difficult-to-reach anatomical locations represent a difficult task in terms of treatment and prediction of the outcome. Radiation therapy is often used for atypical, anaplastic, recurrent, and surgically inaccessible benign meningiomas. However, the method, regimen, dose, and timing of radiation therapy remain uncertain and are areas of active research, with clinical trials ongoing. Currently, there are no universal adjuvant chemotherapy agents, so the latest advances in genomic and epigenomic research of meningiomas are being explored for potential targeted therapy. Advances in genomics and molecular characterization of meningiomas have revealed potential for more detailed classification, description of disease progression, prognosis, and estimation of recurrence rates.

This review aims to analyze and summarize current data on meningiomas, their etiology, molecular characteristics, diagnostics, and treatment methods, and lists currently ongoing clinical trials.

Hereditary genetic syndromes are a significant risk factor for development of oncohematological diseases in childhood. Specifically, Down syndrome is associated with a 500-fold increased risk of acute megakaryoblastic leukemia and a 20-fold increased risk of acute lymphoblastic leukemia compared to the general population. The pathogenesis of leukemia in various hereditary syndromes involves three key mechanisms: impaired DNA repair (as seen in Fanconi anemia, Bloom syndrome), congenital genomic instability (characteristic of ataxia-telangiectasia, Li–Fraumeni, Nijmegen breakage syndrome), and constitutive activation of proliferative signaling pathways (RAS/MAPK pathway in Noonan syndrome and neurofibromatosis type 1).

Specificities of pathogenesis explain therapeutic responses and recommended options in this group of patients. For patients with genomic instability syndromes and bone marrow failure syndromes a 50 % dose reduction of chemotherapeutic agents, complete avoidance of alkylating agents, and exclusion of radiotherapy are recommended. Allogeneic hematopoietic stem cell transplantation remains the only curative treatment option but requires modified conditioning regimens. Contemporary fludarabine-based hematopoietic stem cell transplantation protocols achieve 83 % 5-year survival in Fanconi anemia patients. Emerging innovative therapies (PARP inhibitors, JAK-kinase inhibitors, blinatumomab, tisagenlecleucel) represent promising strategies to enhance treatment efficacy while reducing toxicity.