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Vol 27, No 3 (2022)

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Clinical investigations

High expression of CD8+ T-lymphocytes in the peritumoral zone of renal cancer as a factor of unfavorable prognosis

Bobrov I.P., Lazarev A.F., Cherdantseva T.M., Klimachev I.V., Klimachev V.V., Myadelets M.N., Lepilov A.V., Dolgatov A.Y., Korsikov N.A., Dolgatova E.S., Lushnikova E.L., Bakarev M.A.

Abstract

AIM: To evaluate the prognostic value of quantitative CD8+ T-lymphocyte counts in the peritumorotic zone of renal cell cancer.

MATERIAL AND METHODS: The material of 74 patients after operative treatment for renal cell carcinoma with complete 5-year follow-up was retrospectively analyzed. Of the 74 patients, 56 were alive by the 5-year follow-up, and 18 had died of cancer. After immunohistochemical staining, CD8+ T-lymphocyte distribution density in the peritumorotic zone of carcinomas was determined in 3 representative fields of view at ×400 magnification and correlated with the clinicopathological characteristics of neoplasms and overall 5-year patient survival rate.

RESULTS: The high level of CD8+ T-lymphocyte infiltration in the peritumoral zone of carcinomas was seen in stages III–IV of the disease (p=0.0000001), in tumors >7 cm (p=0.0000001), in Fuhrman grade III–IV anaplasia (p=0.001), in metastases (p=0.0000001) and in the shorter total survival rate of patients (p=0.0003). High CD8+ T-lymphocyte count was also observed in men (p=0.001) and in cases of unclassified cancer.

CONCLUSION: In the light of the need to search for new prognostic criteria in renal cancer, we conclude that a high level of peritumorous zone infiltration by CD8+ T-lymphocytes is an unfavorable prognostic factor. Assessment of peritumorous zone infiltration by CD8+ T-lymphocytes may serve as an additional prognostic factor in renal cell carcinoma.

Russian Journal of Oncology. 2022;27(3):97-105
pages 97-105 views

Intracranial hemangiopericytoma: long-term surgical outcomes

Andrushkevich O.M., Anisimov E.D., Zotov A.V., Gormolysova Е.V., Uzhakova E.K., Kasymov А.R., Abdilatipov А.А., Galushko Е.V., Kalinovskiy A.V.

Abstract

BACKGROUND: According to 2021 WHS Classification, intracranial hemangiopericytomas or solitary fibrous tumors are rare meningeal neoplasms involving blood vessels and soft tissues. Such neoplasms are commonly classified as malignant due to their aggressive growth, metastasizing beyond the cranial cavity, and frequent recurrencies. Since these tumors rarely occur in neurosurgical patients, publications in Russian do not cover big cohorts of patients whose conditions would be assessed during both early and late observation periods.

AIM: The present study analyzed our experience in surgical treatment of hemangiopericytomas and its long-term results.

METHODS: The study was arranged as a single-center, pro-and retrospective trial that included hemangiopericytomas patients (n=17), whose tumors of different grades of malignancy (1–3) were operated at the Federal Neurosurgical Center in Novosibirsk from 2013 to 2021. The follow-up estimates included survivability; physical status (Karnofsky’s Scale); radicality; metastatic foci; need for postoperative chemo-and radiation therapy; adjuvant therapy effect on patients’ survivability, and delaying time to relapse.

RESULTS: In total, 17 patients were included. 11 of them underwent total hemangiopericytomas removal (65%), and 6 — subtotal removal (35%). Their survivability within the first year after the operation was 100%. As for the 5-year follow up, only 8 patients out of 17 were available, their mean observation time comprising 64.7 months. The 5-year survivability was 75% (6 out of 8 patients). A relapse occured in 3 out of 17 (17.5%). The mean delaying time comprised 67 months. 6 out of 17 patients (35%) underwent radiation therapy. Among the patients with total and subtotal removals who underwent postoperative radiation treatment neither a relapse nor tumor growth nor metastases were found.

CONCLUSION: Intracranial hemangiopericytoma is a rare malignant space-occupying neoplasm. Considering our experience and published data, its treatment requires aggressive tactics that includes a radical removal of the tumor followed by early irradiation of the tumor’s residual volume or bed either in a proton accelerator or a gamma-knife facility notwithstanding its malignancy grade. It is also recommended to extend the follow-up period for such patients to 10–15 years that should include annual cancer screening to detect local relapses and metastases.

Russian Journal of Oncology. 2022;27(3):107-116
pages 107-116 views

Reviews

Palliative treatment of pancreatic cancer

Tseimakh A.E., Lazarev A.F., Shoykhet Y.N.

Abstract

Pancreatic cancer is one of the most serious problems of modern oncology. In the Russian Federation, pancreatic cancer, along with a fairly small share in the structure of the incidence of malignant neoplasms — 3%, ranks first in annual mortality (68.2%), and is also a nosology with the most unfavorable prognosis among tumors of the gastrointestinal tract. The current standard of first-line therapy is FOLFRINOX (FOLFIRINOX, a combination of 5-fluorouracil (5-FU), leucovorin, irinotecan, and oxaliplatin) or gemcitabine plus albumin-bound nab-paclitaxel.

One of the main obstacles to the action of chemotherapeutic drugs is the microenvironment of fibro-solid stromal tumors, which include pancreatic cancer. In order to potentiate the action of chemotherapy and combat the tumor microenvironment, at the present stage, drugs are being considered for influencing the programmed death 1 (PD-1) gene and cytotoxic T-lymphocyte antigen 4 (CTLA-4). Approximately 10–15% of malignant neoplasms of the pancreas are believed to be associated with hereditary mutations, while all neoplasms have somatic mutations in different combinations of driver genes. One of the most common mutations are BRCA1/BRCA2 gene mutations. Poly-ADP-ribose polymerase inhibitors, like cisplatin, have shown promise as a treatment for tumors with BRCA mutations.

Another subtype of pancreatic cancer is characterized by microsatellite instability. Unlike the above mutations and phenotypes, which affect only a small proportion of patients with pancreatic cancer, mutations in KRAS (Kirsten homologous rat sarcoma viral oncogene) are found in 90–95% of cases of pancreatic malignancy and may be a significant factor in pancreatic tumorigenesis. Another frequently mutating gene for a number of malignancies is ARID1A, which encodes a tumor suppressor protein, a subunit of the SWI/SNF chromatin remodeling complex.

The future of conservative therapy for pancreatic cancer is a complex treatment that includes both chemotherapy and targeted therapy and immunotherapy, the implementation of which is impossible without a deeper study of genetic mutations, molecular mechanisms of invasion and development of pancreatic malignant neoplasms, as well as extensive testing for genetic mutations in the clinical practice of specialized institutions.

Russian Journal of Oncology. 2022;27(3):117-126
pages 117-126 views

Modern outlook for the use of photosensitizers with aggregation-induced emission in treatment of malignant tumors

Tseimakh A.E., Lazarev A.F., Shoykhet Y.N.

Abstract

Photodynamic therapy (PDT) is actively developing, becoming one of the important methods of non-invasive treatment of various oncological and infectious diseases. It is usually carried out using three main components: a photosensitizer, light, and oxygen. The key factors for the effective use of PDT are reactogenic oxygen species, which are produced during the oxidation of photosensitizers under the influence of light irradiation.

To increase the production of reactogenic oxygen species, a technique was proposed for creating photosensitizers with aggregation-induced emission. At the present stage in oncology, the following PDT methods using photosensitizers with aggregation-induced emission are distinguished: PDT, absorbing near infrared radiation; enzyme- or glutathione-activated PDT; hypoxic PDT, and synergistic therapy.

Compared to visible light, near infrared radiation (700–1700 nm) has been shown to be more effective and safer due to reduced photodamage, less scattering, and deeper light penetration. The development of activated photosensitizers is an effective way to overcome the uncontrolled phototoxicity of photosensitizers during long-term PDT in vivo, providing controlled death of tumor cells. The oxygen concentration in tumor tissue varies depending on tumor progression, angiogenesis, metabolism, and metastasis. Therefore, the development of photosensitizers capable of effectively fluorescing under hypoxic conditions, including catalyzing intracellular substrates with the formation of oxygen and stimulating the production of reactogenic oxygen species through the type I mechanism, has become a potential solution to the problem of PDT of solid tumors.

The therapeutic efficacy of a single PDT method, as well as most treatment methods in modern oncology, is limited. Therefore, a significant direction is the development of multifunctional treatment systems for synergistic therapy of tumors. Synergistic chemotherapy and PDT is an important area of treatment in oncology. The combination of PDT and immunotherapy is also a promising direction in the treatment of malignant neoplasms.

There are obvious prospects for PDT in oncology not as a separate method of treatment, but as part of a complex multimodal treatment, including chemotherapy, radiation therapy, surgical treatment, and immunotherapy.

Russian Journal of Oncology. 2022;27(3):127-135
pages 127-135 views

Case Reports

Surgical treatment of primary synovial lung sarcoma: a case report

Novikov D.V., Chekini A.K., Novikova A.О.

Abstract

Synovial sarcoma is a rare aggressive malignant mesenchymal tumor that accounts for 2.5–10.0% of all sarcomas and is most often found in the soft tissues of the extremities, especially near large joints. Primary synovial lung sarcoma is quite rare and accounts for 0.5% of all primary malignant lung neoplasms. The tumor is sensitive to chemotherapy, but the main method of treatment of synovial lung sarcoma remains surgical. Publications devoted to this topic, are presented by clinical observations due to the rare occurrence of the disease, therefore, each such observation is of scientific and practical interest.

We present a clinical case 65-year-old patient with a tumor of the right lung with a diameter of more than 25 cm. Repeated attempts to perform transthoracic puncture both in our department and in other hospitals for the biopsy were unsuccessful. Taking into account the progression of the disease, the appearance and increase of the respiratory failure clinic, the impossibility to exclude the malignant nature of the process and the good functional status of the patient, a decision for surgery was made. The patient underwent right pneumonectomy with mediastinal lymph node dissection. The postoperative period was complicated by intrapleural bleeding, for which a rethoracotomy was performed. After recovery, the patient was discharged from the hospital in a stable condition.

Russian Journal of Oncology. 2022;27(3):137-142
pages 137-142 views


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