Journal of Modern Oncology

Oncology is one of the undisputable leaders of the present day medicine in terms of innovations and research. Globalization and a high number of randomized clinical trials generate an ever increasing amount of new data, clinical guidelines on cancer treatment, complications prevention and supportive care. Modern oncology practice demands vast and firm knowledge on venous thromboembolism treatment and prevention. The article is a survey of the present day clinical guidelines and real world data in the field of cancer-associated thrombosis.

Background. Prior to the introduction of new agents — immune checkpoint inhibitors — for inoperable and/or metastatic melanoma (IMM), chemotherapy outcomes were generally poor. The median (Me) overall survival (OS) in IMM was no more than 6-9 months, and the Me of progression-free survival (PFS) was about 2 months. The introduction of immune checkpoint inhibitors and targeted therapy changed the prognosis for the life of IMM patients dramatically. The development, studies, and approval of a new original PD-1 inhibitor, prolgolimab, in Russia in 2020 prompted the professional community to conduct a prospective observational study in the Russian Federation to assess its real-world efficacy and safety.

Aim To evaluate the real-world efficacy and safety of prolgolimab in patients with IMM.

Materials and methods. From October 2020 to October 2022, 700 patients with IMM receiving prolgolimab in real clinical settings in oncological institutions of various levels in the Russian Federation were included in the study. The main inclusion criteria were: pathology-confirmed diagnosis of melanoma; metastatic and/or inoperable type; use of prolgolimab outside of clinical trials; and signed informed consent. Objective response rate in the general population and the Intention-to-treat and Per Protocol populations was considered the main criterion for evaluating the efficacy of therapy, and the safety criterion was the incidence of grade 3-4 adverse events (AEs). PFS and OS rates were also assessed. Statistical analysis was performed using the SPSS 25.0 software package.

Results. The objective response rate for the Per Protocol population (with radiographic assessment available) was 42% (n=235/559). Disease progression was reported in 26.7% (n=149) of patients, stabilization in 31.3% (n=175), and disease control in 73.3% of patients with IMM, regardless of the line of therapy. At the follow-up Me of 12 months (0-36), PFS for all patients regardless of the line of therapy was 8 months (95% confidence interval [Cl] 6.537-9.463), 6-month PFS was 55%, and 12-month PFS was 41%. OS Me for all included patients was 32 months, 6-month OS was 82%, and 12-month OS was 69%. Depending on the line of therapy, the OS Me was: line 1 - not reached, line 2-30 months (95% Cl 16.007-43.993), line 3 and subsequent- 22 months (95% Cl 14.264-29.736); p=0.736. According to the CTCAE 5.0 general terminology criteria for AEs, a total of 136/693 (19.6%) AEs of varying degrees were reported, in particular: grade 1-2 - 105/693 (15.2%), grade 3-4 - 25/693 (3.6%), unknown grade - 5/693 (0.7%), as well as one fatal case (0.1%) due to thromboembolism in the vascular center with an unclear (according to the investigator's assessment) relation with prolgolimab.

Conclusion The results obtained at 12 months of follow-up confirm the high efficacy and satisfactory tolerability of prolgolimab in patients with IMM in real-world practice, regardless of the line of therapy and other characteristics.

Aim To evaluate the safety and toxicity of lenvatinib with pembrolizumab in unselected patients with advanced renal cell carcinoma (RCC).

Materials and methods. The Russian phase IV observational study included 151 patients with advanced RCC who received lenvatinib with pembrolizumab in a standard dose regimen in 36 clinical centers of the Russian Federation. Most patients were diagnosed with clear cell RCC (n=145, 96.0%), with synchronous (n=77,51.0%) metastasesof more than one location (n=111,73.5%), removed primary tumor (n=98, 64.9%) and were classified into intermediate and poor IMDC prognostic groups (n=111, 73.5%). Median follow-up was 9.6 (1—68) months.

Results. Any adverse events (AEs) were noted in 109 (72.2%), grade ≥3 AEs-in 26 (17.2%), serious AEs-in 9 (6.0%) of 151 patients. There were no deaths caused by AEs. AEs were an indication for lenvatinib dose reduction in 32 (21.2%), a dose interruptions in lenvatinib treatment in 21 (13.9%), and lenvatinib discontinuation in 2 (1.3%) cases. A dose interruptions in pembrolizumab therapy due to AEs was necessary in 15 (9.9%) cases. Both combination drugs were discontinued due to toxicity in 10 (6.6%) cases. AEs were assessed as immune-mediated in 24 (15.9%) patients (grade 3-4 - n=7, 4.6%) and required the prescription of high doses of glucocorticosteroids in 2 (1.3%) patients.

Conclusions. A Russian observational study confirmed the acceptable safety profile of lenvatinib plus pembrolizumab therapy in patients with advanced RCC.

Background. The use of cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors in combination with endocrine therapy is a key initial treatment for advanced luminal HER2-negative (HR+/HER2-) breast cancer. The approval studies MONALEESA-2 and 7 demonstrated the efficacy and safety of ribociclib in combination with aromatase inhibitors as a first-line treatment in post- and premenopausal patients. In the Phase lllb CompLEEment-1 study, the same treatment regimen was evaluated in an extended patient population in terms of both safety and efficacy. The article presents an analysis of data from a subgroup of patients from Russia.

Materials and methods. The study included 129 patients from Russia who met the inclusion criteria for the CompLEEment-1 study. The primary endpoint was the incidence of adverse events (AEs) at a median follow-up of 25.4 months. Secondary endpoints were median progression-free survival, objective response rate, and disease control.

Results. The efficacy and safety results of the therapy in the subgroup of patients from Russia were consistent with the general population of patients included in CompLEEment-1. The incidence of AEs requiring dose adjustment or treatment interruption was 58.1%, and the permanent discontinuation rate was 15.5%. The most frequently reported treatment-related AEs grade 3 or higher were neutropenia and transaminase increased.

Conclusion Data obtained in a subgroup of patients from the Russian Federation confirm the safety and tolerability of ribociclib in an extended population of patients with HR+/HER2- breast cancer in settings close to the real world.

In the modern world breastfeeding (BF) is considered as a significant factor in reducing the risk of developing malignant tumors of the mammary gland and ovaries. However, the problem of maintenance or refusing BF in malignant neoplasms (malignant neoplasms) still remains open. In recent years, there has been a steady increase in breast cancer (BC), especially in developed countries, with more than 10% of all breast malignancies (BC) diagnosed in women under 40 years of age. The presented article highlights aspects of maintaining lactation in different periods of the relevance of BF in relation to the timing of manifestation of cancer, and also presents data from the multicenter study POSITIVE (Pregnancy Outcome and Safety of Interrupting Therapy for women with endocrine responsIVE breast cancer) on the possibilities of implementing reproductive function and BF in women receiving therapy for hormone-receptor positive (HR+) BC stages I–III. BF with cancer detected in the postpartum period depends on the treatment of the underlying disease. In patients undergoing surgical treatment, BF is not contraindicated, but it is not always technically possible. During chemotherapy, BF is not recommended. When carrying out radiotherapy, it is possible to undergo BF using a healthy mammary gland. There is currently no evidence to suggest that BF woman diagnosed with cancer may have any negative effects. In general, it has been shown that preserving and maintaining lactation in women with a history of cancer is safe for both mother and child.

Aim. To study the rates of repeated disability due to brain malignancies in the female population in Moscow for 2017–2021 and develop measures to prevent morbidity and reduce disability from these causes.

Materials and methods. The study was continuous; the information database of the Single Automated Vertically Integrated Information and Analytics System for Social Security Medical Assessments of the Main Office of Medical and Social Assessment was used based on the results of a re-examination of female patients with brain malignancies (BM) at the Bureau of Medical and Social Expertise for 2017–2021.

Results. The study of repeated disability of the female population due to brain malignancies in Moscow for 2017–2021 showed an increase in the absolute number and percentage of persons repeatedly recognized as disabled; the predominance of persons of working age (63.8%) with an upward trend; the predominance of disabled people of group II with a tendency to increase in absolute number, proportion and level; the predominance of disabled people of groups II–III among women of working age and groups I–II among persons older than working age.

Conclusion. The study of repeated disability of the female population due to brain malignancies in Moscow for 2017–2021 showed an increase in the absolute number and percentage of persons repeatedly recognized as disabled; the predominance of persons of working age (63.8%) with an upward trend; the predominance of disabled people of group II with a tendency to increase in absolute number, proportion and level; the predominance of disabled people of groups II–III among women of working age and groups I–II among persons older than working age. It indicates the need for preventive measures, screening for early detection of brain malignancies, primarily of the working-age population, with the expansion of high-tech approaches to patients, observing routing at all stages of medical rehabilitation with the introduction of modern technologies.

Aim. To establish the criteria of selection for extracorporeal partial nephrectomy (EPN) among patients with malignant tumors involving renal parenchyma.

Materials and methods. The study included data of 34 patients undergone 36 EPNs (2 [5.8%] bilateral) for absolute indications in 32 (94.2%) and relative indications – in 2 (5.8%) cases. The median age of the patients was 49 (31–61) years, and 24 (70.6%) were males. 33 (97.1%) patients were diagnosed with renal cell carcinoma, 1 (2.9%) – with primary retroperitoneal leiomyosarcoma involving a solitary kidney. No regional metastases were detected in any patients; 2 patients were diagnosed with solitary metastases in the adrenal gland. In all patients EPN was performed (2 [5.8%] – with adrenalectomy); the surgery was completed in 35 (97.2%) patients. No additional anti-tumor treatment was administered in any patient. The median follow-up was 65.6 months.

Results. The median surgery time was 674 (360–870) min, and the median blood loss was 2100 (500–7000) mL. The rate of postoperative complications of EPN was 82.9% (30/35), including 48.6% (17/35) of grade 1–4 and 8.6% (3/35) of grade 5 complications. Severe acute kidney injury was reported in 68.0% (25/33) of patients with completed EPN. Renal replacement therapy was required in 45.5% (15/33) of cases. The rate of postoperative autograft loss was 17.1% (7/35). One patient received intermittent hemodialysis (7 years after EPN). 5-year overall survival of 33 patients with completed EPN was 64.4%; the 5-year specific and disease-free survival of patients with renal cell carcinoma was 85.5% and 54.3%, respectively, and 5-year hemodialysis-free survival in patients discharged with autograft was 76.2%.

Conclusion. EPN is indicated only for carefully selected patients with absolute indications for organ-preserving treatment, with massive multifocal centrally located malignant tumors in the renal parenchyma, the radical removal of which in situ is technically impossible.

Malignancies remain a serious socio-economic health problem worldwide. Among them, breast cancer (BC) in women ranks 1st in the structure and 4th in mortality. Occult breast cancer accounts for 0.1 to 1% of all BC. In this type, metastases to the scalp are extremely rare. This article presents a case of metastatic lesion of the scalp in occult breast cancer. Patient S., 82 years old, presented with a skin tumor in the parietal region, which she noticed about 2 years ago. It has grown recently, with local alopecia and hyperemia around the lesion. A comprehensive examination was performed. Cytology of the punctate showed malignant cells. Mammography and ultrasound showed no specific changes in the breast and lymph nodes. Spiral computed tomography of the chest and abdomen showed no signs of tumor. The lesion was surgically removed. Histological examination revealed adenocarcinoma metastasis. Immunohistochemical examination revealed tumor cells with diffuse and strong expression of estrogen receptors, diffuse and weak expression of progesterone receptors, strong and focal-diffuse expression of cancer embryonic antigen (CEA), and epithelial membrane antigen (EMA). The proliferative activity index of Ki-67 was less than 20%, Her2-neu 0. Considering the morphology and immunohistochemical data, the lesion was a metastasis of breast cancer with a luminal type A molecular biological variant. Skeletal bone scintigraphy revealed no metastatic lesions. The patient was diagnosed with an occult type of breast cancer, stage IV cTxN0M1, with metastasis to the scalp. Hormone therapy with aromatase inhibitors was administered. There were no signs of recurrence during the follow-up for 6 months. Isolated scalp metastasis in occult breast cancer is extremely rare. Practitioners should consider this type of distant metastasis of malignancies in differential diagnosis.

This publication is the Russian translation of the Plain Language Summary (PLS) of the Cochrane Systematic Review: de Boer AGEM, Tamminga SJ, Boschman JS, Hoving JL. Non-medical interventions to enhance return to work for people with cancer. Cochrane Database Syst Rev. 2024;3(3):CD007569. DOI: 10.1002/14651858.CD007569.pub4