卷 26, 编号 4 (2024)

Estrogen receptors are detected in more than 70% of cases of metastatic breast cancer (mBC). Currently, various hormonal therapy options are used to treat these tumors. However, modern oncology faces an acute problem of acquired resistance to hormonal therapy, including late lines of therapy for HR-positive (HR+) and HER2-negative (HER2-) mBC. The common causes of resistance include mutations in the ESR1 gene that are usually absent in the primary tumor. These mutations are associated with aggravation of the disease. Until recently, their detection was only of prognostic value and was not taken into account when choosing the treatment regimen. As the new data become available on the role of mutations in the ESR1 gene and their possible impact on the choice of mBC therapy, it seems appropriate to consider the main criteria for testing and test methods to detect the mutations in routine clinical practice. This review article addresses issues related to optimal treatment for progression of HR+/HER2- mBC during endocrine therapy, taking into account the accumulated data on mutations in the ESR1 gene. We also consider the available data on the studied oral selective estrogen receptor destructors as drugs that significantly increase survival in late lines of therapy for hormone-dependent tumors.

Despite advances in the early diagnosis of breast cancer (BC), the identification of locally advanced forms continues to be relevant. This is a complex category of patients whose treatment includes the complex use of various methods with significant medical and economic costs, long-term treatment and rehabilitation. A particular difficulty is the treatment in cases of progression of locally advanced forms. Patients with locally advanced BC require a multidisciplinary approach. In the absence of an effect after neoadjuvant drug treatment and the impossibility of performing surgical intervention, patients are treated with induction radiation therapy. The article describes the features of induction radiation therapy in the treatment of progression of primary inoperable BC in a specific clinical example. In case of recurrence of triple negative type of BC, the patient underwent various drug treatment regimens with the inclusion of immunotherapy. Due to the lack of effect from 3 lines of systemic drug treatment, it was decided to conduct radiation therapy. In connection with the identified carrier of a mutation in the BRCA1 gene, targeted therapy with PARP inhibitors was prescribed. Two months after radiation therapy and 1 month after the start of targeted therapy, the patient showed complete resorption of the tumor conglomerate on the anterior chest wall. The use of conformal radiation therapy in case of recurrence of the disease and the absence of the effect of systemic treatment made it possible to completely resorb an exophytic tumor with ulceration and achieve remission within the next 6 months.

Aim. To determine the overall survival (OS) and progression-free survival (PFS) rates of patients with ovarian cancer (OC) of stages I–IV, depending on a number of clinical and morphological factors: age, stage of the disease, histological type of tumor, mutations in the BRCA1/2 genes.

Materials and methods. A retrospective analysis of the medical records of 910 patients with OC of stages I–IV who received treatment in the period from 2004–2021 on the basis of the Primorsky Regional Oncological Dispensary was carried out. Data processing, calculations of indicators of OS and time to progression, median life expectancy and PFS, preparation of graphic material were carried out using the Microsoft Excel 2019 and IBM SPSS Statistics 26 software package in the Windows 11 operating system environment. The Kaplan–Meier method was used, the evaluation of Cox proportional hazard models (single-factor) with the calculation of relative risks and 95% confidence interval. The significance of the coefficients of the model was estimated by the Wald criterion.

Results. It has been shown that the age, stage of OC and BRCA status of patients are important clinical and morphological factors determining survival rates and time without tumor progression. The highest rates of OS and PFS were demonstrated by young patients under 50 years of age with stage I–II OC, patients with low-grade serous carcinoma and serous carcinoma without indicating the degree of malignancy. Patients with a mutation in the BRCA1/2 genes had an advantage in terms of OS compared to patients without mutations. The maximum OS and PFS were in patients under 50 years of age, the median OS was 146.0±27.3, the 5-year-old OS was 76.4±2.8% and the median time to progression was 67.0±9.9 months, the 5-year-old PFS was 53.0±3.2%, respectively. In the analysis of survival depending on the histological structure of the tumor, advantages were noted in patients with low-grade serous carcinoma, median pancreas was 143.0±20.5 months, 5-year OS reached 70.2±4.4%, compared with patients with high-grade serous ovarian carcinoma, median pancreas was 70.0±5.5 months, 5-year OS – 55.5±2.7%. Also, benefits in overall survival were observed in patients with BRCA-associated OC, the median pancreas was 82.0±13.8 months versus 58.0±9.0 months in BRCA1/2-negative patients.

Conclusion. In patients with OC of stages I–IV, the median life expectancy was 87.0±6.59 months, five-year overall survival was 61.8±2.0%; median time to progression was 31.0±2.76 months, five-year PFS was 41.5±2.0%. The survival rate of patients consistently worsens with increasing age and stage of OC, reaching a maximum in patients aged 71 years and older and in patients with stage III–IV. The histological type of tumor causes significant differences in OS and PFS in patients with OC. The lowest rates of survival and PFS are inherent in mucinous carcinoma, clear cell OC, and high-grade serous ovarian carcinoma. The benefits are noted in patients with low-grade serous ovarian carcinoma and serous carcinoma without indicating the degree of malignancy. Patients with BRCA-associated OC had significant benefits in overall survival, while there were no significant differences in PFS.

Differentiated thyroid cancer (DTC) has a fairly favorable prognosis and a high overall survival (OS). However, approximately 10-15% of patients develop distant metastases, primarily to the lungs. No uptake of radioactive iodine ¹³¹I during the first course of radioactive iodine therapy (RAI-T) or the absence of a significant response to RAI-T can be noted in 20-50% of patients with advanced forms of the disease, which enables them to be classified as RAI-T-resistant (RAIR). The prognosis for RAIR patients is less favorable, with a 5-year OS of 50%, compared to 10-year OS of up to 98% in nonaggressive forms of DTC. Currently, multikinase inhibitors, mainly targeting vascular endothelial growth factor receptors, are the standard treatment for these patients. However, recent studies suggest that tumor cells can restore the ability to uptake ¹³¹I in the presence of a mutation in the BRAF V600E gene following prior treatment with BRAF-/MEK inhibitors (tumor redifferentiation). The article presents a case of a 56-year-old patient diagnosed with papillary thyroid cancer. During the observation, the disease progression was noted due to the growth of distant metastases to the lungs after two courses of RAI-T with a total activity of ¹³¹I 9.3 GBq, confirming RAIR. Molecular genetic study of the primary tumor tissue block revealed a mutation of the BRAF V600E gene. An oncological team board was held at the National Medical Research Center for Endocrinology, and the patient was offered therapy with targeted BRAF-/MEK inhibitors. After 6 weeks of therapy, the diagnostic whole-body scintigraphy with ¹³¹I showed increased uptake in the lungs, prompting a repeated course of high-dose RAI-T with an activity of 7.5 GBq. Six months following treatment, radiological improvement was observed: partial response with a reduction in the size of metastatic lung lesions by 40% at the time of data publication. The patient continued targeted therapy due to the absence of severe adverse events. Thus, BRAF-/MEK inhibitors combined with RIT can be considered as an option in patients with RAIR DTC. This strategy can potentially significantly improve both prognosis and and quality of life in patients with aggressive forms of DTC.

Aim. To evaluate the efficacy and safety profile of the pembrolizumab biosimilar, Pembroria, in patients with advanced lung cancer in routine clinical practice.

Materials and methods. The patients eligible for pembrolizumab therapy based on standard clinical indications and without contraindications participated in the multicenter, multicohort, post-marketing, prospective, non-interventional study. The primary endpoint was the best objective response rate (ORR) assessed within six months of treatment initiation. This report presents interim analysis for patients with non-squamous non-small cell lung cancer (nsNSCLC) and squamous non-small cell lung cancer (sNSCLC) using Fleming’s two-stage single-arm design (stages g1 and g2). Thresholds for hypothesis testing and sample size determination were based on established literature benchmarks.

Results

Non-squamous NSCLC. Stage g1 enrolled 20 patients with a median age of 64 years. The follow-up period for assessing the best objective response was 2.57 months. An objective response was achieved in 55% (11/20) of patients, meeting predefined efficacy criteria at stage g1.

Squamous NSCLC. Stage g1 included 23 patients and based on the results of stage g1, the study proceeded to stage g2 with the enrollment of an additional 23 patients in stage g2, yielding a total of 46 participants with a median age of 66 years. An ORR of 47.8% (22/46) was observed, confirming efficacy of the pembrolisumab biosimilar at stage g2. The median follow-up period to the objective response assessment was 2.88 months.

Across the six-month follow-up period, nine adverse events (AEs) were reported among seven patients (8.4%) in the NSCLC cohort. Four AEs were considered therapy-related and classified as Grade 2 per CTCAE v5.0. No AEs Grade 4/5 were recorded.

Conclusion. In the NSCLC cohort, the pembrolizumab biosimilar (Pembroria) has demonstrated an ORR comparable to that of the reference pembrolizumab reported in clinical trials for both nsNSCLC and sNSCLC, regardless of PD-L1 expression levels or pembrolizumab treatment regimens. These findings support the real-world efficacy and safety of Pembroria in a diverse patient population.

Aim. To study the reasons for prescribing antitumor drugs (ATDs) beyond the registered indications (BRIs) in real clinical practice.

Materials and methods. The study was conducted at the Tula Regional Clinical Oncology Center. For 6 months of 2019, information was analyzed on 919 completed cases of treatment of 201 patients over the age of 18 who received antitumor drug therapy for morphologically verified solid malignant neoplasms in the inpatient department of the medical organization using a regional information system. Completed cases of treatment with ATDs were copied BRIs and in accordance with the registered indications. The analysis of the literature devoted to the study of the causes of the use of ATDs outside the registered indications has been carried out. The reasons for prescribing ATDs BRIs in real clinical practice were studied when analyzing completed cases of treatment of patients receiving appropriate therapy.

Results. In 86.2% of cases, the main reason for the use of antitumor drug therapy BRIs is associated with the presence of antitumor agents in clinical guidelines and recommendations of professional communities. 11.6% of cases of prescribing antitumor agents BRIs were associated with burdened clinical situations: exhaustion of the possibilities of registered therapy; lack of treatment options for rare forms of neoplasms; lack of alternative options with contraindications to standard treatment methods. Other reasons for prescribing the above mentioned treatment were extremely rare and were situational in nature.

Conclusion. In the vast majority of cases, the main reason for prescribing ATDs BRIs is the presence of these agents in clinical guidelines and recommendations of professional communities. The second most common cause is associated with burdened clinical situations. The information obtained indicates that the use of ATDs in cancer patients is an integral part of routine clinical practice and in the future can be used to improve the regulatory regulation of these prescriptions.

Non-Hodgkin's lymphoma can occur anywhere in the human body. A diffuse extensive peritoneal lesion is uncommon and rare. Diffuse large B-cell lymphoma is the most common histological type of extranodal lymphoma in peritoneal lymphomatosis.

A case of isolated peritoneal lymphomatosis is presented. A 23-year-old female patient N. presented with decreased appetite, bloating, pain, and abdominal enlargement. The symptoms persisted for 4 months. Recently, she reported a fever (38.4°C), sweating at night, and decreased body weight. On physical examination, the abdomen was enlarged, tense on palpation, tender in the epigastrium, and dull to percussion in all parts. No signs of specific changes in peripheral lymph nodes were observed. Tachycardia was noted, and blood pressure was within normal range. Five weeks ago, a laparoscopy was performed, which revealed an extensive infiltrative lesion of the parietal and visceral peritoneum of the abdomen and pelvis and the greater omentum with the presence of mesenteric lymph nodes. A biopsy of the peritoneum and greater omentum was performed. Cytological examination of ascitic fluid showed a pattern of non-Hodgkin's lymphoma. Histological examination revealed diffuse large B-cell lymphoma with CD20+ expression. Positron-emission and X-ray computed tomography with 18-fluorodeoxyglucose (FDG) showed diffuse thickening of the parietal and visceral peritoneum, mesentery and omentum with subtotal filling of the abdominal and pelvic cavities with masses with increased radiopharmaceutical uptake. No FDG-active lesions were detected in the liver and spleen parenchyma. Diagnosis: diffuse large B-cell lymphoma, stage IVB; peritoneal lymphomatosis, IPI 3. Polychemotherapy was recommended according to the R-CHOP regimen. The patient refused the proposed treatment due to the change of domicile.

Isolated peritoneal lymphomatosis is a rare manifestation of extranodal non-Hodgkin's lymphoma. There are no specific clinical symptoms. Positron emission and X-ray computed tomography with 18-FDG are an alternative method for diagnosing peritoneal lymphomatosis.

Aim. The objective of the study is to evaluate the clinical efficacy and safety of PRFA (pulsed radiofrequency ablation) of nerve roots in improving general somatic and functional status (Karnofsky score), decreasing pain (NRS) and reducing analgesics consumption (Watkins score) in patients with spine metastatic lesions.

Materials and methods. This study involved the analysis of 230 patients with pain syndrome related to metastatic lesions in the spine. Those patients were divided into two groups. The first group included 156 patients who underwent Pulsed RFA of nerve roots in order to relieve pain. There were 69 men and 87 women. The second group, which received only drug treatment with non-opioid and opioid analgesics, consisted of 74 patients, including 30 men and 44 women. The performance status was evaluated with the Karnofsky score (%), pain degree was assessed with the Numerical Rating Scale from 0 to 10 (NRS), and analgesics consumption reduction was assessed by the Watkins scale. Overall treatment satisfaction in patients and physicians was evaluated with the Likert scale.

Results. In the pulsed RFA group, 124 (79.5%) patients out of 156 had effective therapy in the form of NRS decrease of at least 50% and at least 1 point decrease by the Watkins scale. The performance status improved by at least 10% according to the Karnofsky index in 121 (77.6%) patients. As for the control group, the effectiveness of pharmacotherapy based on NRS was achieved in 65 (87.8%) out of 74 patients, and the general somatic status was improved in 60 (81.1%) patients. The maximum analgesic effect of the nerve root RFA is achieved on the 10th day after the procedure, maintaining for up to 90 days without dynamics. The level of statistical significance was p<0.001. In the RFA group, 153 (98.01%) patients experienced no complications, and in the control group, complications were seen in 64 (86.5%) cases, manifested themselves in the form of adverse events from analgesics used for pain control. Originally, prior to the study, all 100% of patients in both groups expressed pain therapy dissatisfaction before consulting a vertebrologist. The unsatisfactory score proportion on the Likert scale during the treatment in the RFA group decreased to 20.5% (32), and in the pharmacotherapy group – to 28.4% (21), respectively.

Conclusion. Pulsed radiofrequency ablation of nerve roots is highly effective and safe, minimally invasive neuromodulatory method for pain treatment in cancer patients with nerve roots compression caused by the spine metastases. This method allows within a short period to reduce or decrease the severity of pain syndrome in 79.5% of patients, contributing to their physical activity increase and improving the quality of life in 77.6% of patients. Pulsed RFA of nerve roots has advantages over conservative treatment in various aspects: decrease in pain syndrome intensity, enhanced patients satisfaction with treatment results, significant pharmacological stress and its associated complications reduction, improved patients physi-cal activity and quality of life.

Metastases of malignant neoplasms into the penis from various primary locations are extremely rare. These lesions are due to the disseminated tumor. In most cases, the primary tumors are located in the genitourinary system (75%), gastrointestinal tract (21%), and lungs (7%). The prognosis is poor, with most patients dying within a year of diagnosis. The purpose of the article is to present a rare case of metastatic lesion of the penis in adrenocortical cancer. A 59-year-old patient with a stage III right adrenal tumor pT3N0M0 had undergone an adrenalectomy. Histological and immunohistochemical studies showed the classic version of adrenocortical cancer with Ki-67 40%. Mitotane with polychemotherapy according to the EP-M scheme was administered for the adjuvant purpose. In 3 months, the patient developed induration and local soreness in the root of the penis. Magnetic resonance imaging of the pelvic organs showed a hypodense zone in the cavernous bodies. Combined positron-emission and X-ray computed tomography with 18-fluorodeoxyglucose showed a mass in the left cavernous body with increased radiopharmaceutical uptake. Specific lesions were found in the mediastinal and retroperitoneal lymph nodes, liver, bed of the removed tumor, and soft tissues of the lumbar region. Tumor generalization with multiple synchronous metastases, including the penis, was established. Cytological examination of the punctate showed malignant cells. Palliative polychemotherapy was administered according to the EDP-M regimen with glucocorticoids. The treatment had no effect. The patient died 7 months after the establishment of penile metastasis. This case of a penile metastatic lesion in a patient with primary adrenocortical cancer is presented for the first time in the available literature. The main symptoms of the disease are the presence of a tumor in the area of the root of the penis and local pain. Magnetic resonance imaging and combined positron emission and X-ray computed tomography with 18-fluorodeoxyglucose are methods of choice for medical imaging that reliably determine the tumor extension. The location of the primary tumor outside the pelvis in a patient with penile metastases is usually accompanied by multiple synchronous metastases involving other organs.