Vol 24, No 3 (2022)

In the Russian Federation, tetrapeptide tyrosyl-D-arginyl-phenylalanyl-glycine amide (Tafalgin), a novel analgesic, selective agonist of μ1-opioid receptors, was developed and approved in 2022. The article presents the first experience of the successful use of Tafalgin in treating chronic pain in a cancer patient with poor tolerance to traditional opioids (tramadol, tapentadol, morphine). At baseline, pain severity, according to the Neurological Rating Scale (NRS), was 5–7 points at rest and up to 9 points in motion out of the maximum 10. The combination of 400 mg/day of tramadol with gabapentin and a non-steroidal anti-inflammatory drug was ineffective; 400 mg/day of tapentadol in combination with gabapentin and a non-steroidal anti-inflammatory drug also was ineffective. Morphine tablets 60 mg/day were effective (NRS score of 2–3), but unrelenting nausea and vomiting were unmanageable and significantly reduced quality of life. Reducing the dose of oral morphine to 20 mg/day mitigated adverse events but reduced the effectiveness of pain relief (resting NRS score of 4 points). Tafalgin 4 mg subcutaneously BID, then TID reduced the pain severity to an average daily NRS score of 1.22 over the first 3 days of treatment with no adverse events. Sleep, appetite, and physical activity improved. The patient received Tafalgin for 84 days, and she gained 5 kg due to improved nutrition during that time. The drug is comparable in efficacy to morphine and is associated with fewer adverse events. A limitation to widespread use is the availability of a formulation for subcutaneous injection only.

Background. Radiation-induced malignancies are one of the long-term complications of radiation therapy, which is widely used to treat some tumors. The latency period before a second tumor develops varies from 3 to 60 years. Epithelial tumors and hemoblastoses occur after low-dose radiation therapy and sarcomas after high-dose radiation therapy.

Aim. To present a case of radiation-induced soft tissue angiosarcoma of the neck after the cure of Hodgkin's disease.

Materials and methods. A 41-year-old patient with Hodgkin's nodular lymphoma with the lymphoid predominance of stage IIIA with involvement of the right cervical and clavicular lymph nodes, mediastinum, and abdominal lymph nodes was followed-up. In 2004 the patient underwent four cycles of polychemotherapy per ABVD regimen followed by radiotherapy of the right cervical and clavicular lymph nodes and mediastinum, with a total focal dose of 40 Gy.

Results. Seventeen years after the treatment for Hodgkin's disease, including radiation therapy, the patient presented with painful swelling of the neck soft tissues in the radiation area with the transition to the anterior thoracic wall and an enlarged cervical lymph node. A lymph node dissection was performed. According to the combined positron emission tomography and X-ray computed tomography (PET/CT), histological and immunohistochemical studies, epithelioid angiosarcoma of soft tissues of the neck and thoracic wall stage IV cT2N1M1G3 with metastases to the skeleton bones, neck lymph nodes, left adrenal gland was established. Surgical treatment was not performed due to advanced disease. The patient received six cycles of polychemotherapy with doxorubicin + ifosfamide. PET/CT confirmed partial tumor regression.

Conclusion. Radiation-induced soft tissue sarcoma is a late iatrogenic complication of radiation therapy for Hodgkin's lymphoma. The tumor occurred in the radiation area. PET/CT is the method of choice in diagnosing and evaluating the extent of cancer and response to treatment. Chemotherapy, as an option for complex treatment, can achieve adequate disease control when surgery is not feasible.

Tumors of the mediastinum is a collective term that includes neoplasms of various degrees of malignancy, different morphogenesis, originating from heterogeneous tissues and combined into one nosological form according to anatomical localization. Angiosarcoma is a rare malignant tumor originating from a vessel wall. In the general structure of sarcomas, its frequency is estimated at 1%. The tumor is characterized by an aggressive course, local recurrence, hematogenous metastasis, poor sensitivity to chemotherapy and radiotherapy. Surgery remains the main treatment for angiosarcomas. The article presents a clinical case. A 55-year-old patient has multiple primary malignant neoplasms: cancer of the body of the uterus pT1aN0M0 IA stage. Surgical treatment from 12.15.2020 – panhysterectomy; angiosarcoma of the anterior mediastinum with lesions of the manubrium, body of the sternum and the 1st rib on the left, invasion into the left brachiocephalic vein with the formation of a tumor thrombus in it, growing into the upper lobe of the left lung, T3N0M0, G1. Surgical treatment from 08.12.2021 – resection of the manubrium and body of the sternum with resection of the anterior segments I, II, III ribs on both sides, resection of the left brachiocephalic vein, removal of an anterior mediastinal tumor, atypical resection of the upper lobe of the left lung en bloc, reconstruction of the sternum and ribs with an individual titanium 3D prosthesis. The patient was discharged from the hospital in a satisfactory condition.

Background. The indication for radiotherapy in oncological practice are metastases of differentiated thyroid cancer after thyroidectomy, the presence of distant metastases, or stage N1b, or negative dynamics of blood thyroglobulin levels after thyroidectomy for thyroid cancer. The mechanism of action of radiotherapy is based on provoking double-stranded DNA breaks. It is important to study the role of polymorphisms of NFKB1, ATM, ATG16L2 and ATG10 genes, products of which are involved in the processes of DNA damage response pathway and autophagy, in the formation of resistance to radioiodine therapy of thyroid cancer patients.

Aim. To examine the association between NFKB1, ATM, ATG16L2 and ATG10 polymorphisms and resistance to radioiodine therapy in thyroid cancer patients.

Materials and methods. The study included 181 patients (37 men, 144 women; mean age 53.5±15.7 years) with histologically confirmed thyroid cancer and a history of thyroidectomy who received radioiodine therapy. Carriage of single-nucleotide polymorphisms (rs230493) NFKB1, (rs11212570) ATM, (rs10898880) ATG16L2 and (rs10514231, rs1864183, rs4703533) ATG10 was determined by real-time PCR using TaqMan™ kits.

Results. Among 181 patients, resistance to radioiodine therapy was observed in 11 (6.1%) cases. No significant associations between the individual polymorphisms and resistance to radioiodine therapy were obtained, p>0.05. Haplotype analysis showed that carriage of the C-C ATG10 rs10514231-rs1864183 haplotype was associated with an increased risk of developing resistance to radioiodine therapy, p=0.04.

Conclusion. Further studies on large samples of radioiodine therapy-resistant patients using whole-genome sequencing methods are required to specify the role of genetic factors in the response to ¹³¹I therapy.

Background. Transferrin receptor 1 (TfR1) expression has been identified in a number of malignant tumors. It is noted that its overexpression gives growth advantages to cancer cells. Estimation of transferrin receptor expression in breast cancer (BC) might be an important component in disease prognosis, choice of treatment, also might be an attractive target for targeted therapy.

Aim. To evaluate the expression of TfR1 by BC cells and to study its relationship with the clinical, morphological and immunophenotypic characteristics of the tumor.

Materials and methods. This study included 82 patients with BC who received treatment at the Blokhin National Medical Research Center of Oncology (Moscow). The expression of TfR1 on primary tumor cells was studied, the relationship of TfR1 with clinical, morphological and immunophenotypic characteristics of BC was analyzed. Immunophenotyping of the primary tumor was performed by the immunohistochemical method (immunofluorescent staining) on cryostat sections. Antibodies to CD71, CD95, CD54, CD29, MUC1, Pgp170 were used. The reaction was evaluated using a luminescent microscope (AXIOSKOP, Germany). The study was dominated by patients with stage IIB – 54% and IIIB – 21%. Infiltrative ductal BC was diagnosed in 67% (n=55) of patients, infiltrative-lobular – in 22% (n=18) of cases, other types – in 11.0% (n=9).

Results. BC cells expressed TfR1 in most cases (64.4%; n=61). A combination of TfR1 monomorphic expression with MUC1 monomorphic expression (74.4%; n=47) was noted. CD29 is presented both mosaic (38.7%) and monomorphic (51.6%). The Pgp170 antigen was monomorphically observed in 27.5% of cases. As the proportion of TfR+ cells increased, the expression frequency of the adhesion molecule CD54 increased from 10.5 to 33.3%, a positive correlation was established (r=0.293; p=0.008). In the group with TfR1 monomorphic expression, the frequency of tumors expressing the CD95 apoptosis molecule decreased: 25.0% vs 13% (p=0.042).

Conclusion. BC cells overexpress TfR1. TfR1 expression is associated with tumor immunophenotype.

Background. In 15-20% of patients, breast cancer is characterized by the absence or negligible expression in malignant cells of molecular therapeutic receptor targets of three key types: estrogen receptors, progesterone receptors, human epidermal growth factor receptor-2 (triple negative breast cancer – TNBC). At the 2021 conferences of the American and European Societies of Clinical Oncology (ASCO and ESMO) and the San Antonio Breast Cancer Symposium (SABCS), held from December 7 to 10, important advances in new approaches to the treatment of heterogeneous TNBC cohort were announced.

Aim. To find and summarize the most striking results of clinical studies on new treatment options for TNBC patients based on the SABCS 2021.

Materials and methods. We searched the databases of the digital medical education platform MEDtalks (Hilversum, The Netherlands) and the PubMed/Medline database and analyzed the results published in 2021-2022.

Results. We systematized some results of clinical studies on drug therapy in patients with TNBC, discussed at SABCS 2021 (December 7-10, San Antonio, USA). There are now promising results from innovative clinical studies worldwide to identify the optimal approach to the selection of differentiated targeted and immunotherapies for the treatment of TNBC patients: OlympiA, KEYNOTE-522, cTRAK TN Phase II, KEYNOTE-355, NIMBUS, TROPION Phase I study.

Conclusion. Considering the molecular and histological heterogeneity of TNBC, it is reasonable to identify subgroups of patients with some quantitative and qualitative clinical characteristics for further identification of effective personalized treatment regimens. Additional clinical studies and multivariate analysis of data in the subgroups of patients with TNBC, as well as individualized treatment cases, using current methodological tools will contribute to solving the issues in the management of this category of patients.

Among the multiple primary malignant tumors, breast cancer is the most common and in most cases it is combined with the second mammary gland, uterine body, stomach, colon, skin and ovary. Breast angiosarcoma is a very rare disease with unfavorable prognosis. Radiation therapy to the area of the breast is considered to be the main risk factor for the radiation-induced angiosarcoma. Diagnosis is based on the clinical aspect, the results of morphological and immunohistochemical findings. There are no uniform standards for the treatment of this pathology; a surgical method, systemic therapy, and radiation therapy are used. The article presents a clinical case of a female patient born in 1952, who was diagnosed with synchronous multiple primary cancer in 2014: stage 2A left breast cancer (cT2N0M0); bladder cancer – stage I (cT1cN0M0). After the complex treatment, the patient received adjuvant endocrine therapy with Tamoxifen. In December 2018, single bluish formations appeared in the area of the postoperative scar, followed by a rapid growth of formations on the skin within a month, with a tendency to merge and necrosis. The patient was sent for biopsy of the formations with suspected recurrence of the disease. Immunomorphological patterns correspond to the angiosarcoma in the skin of the mammary gland. A simple mastectomy was performed. After 3 months, growth of angiomyosarcoma in the soft tissues of the anterior chest wall continued. Excision of the tumor in the soft tissues of the chest was performed and the patient underwent postoperative course of radiation therapy with a single focal dose (SFD) 2.5 Gy, total boost isodose of 50 Gy. At follow-up examinations held from January to December 2021, there is no evidence for continued growth and recurrence of the disease. The presented clinical observation demonstrates the experience of diagnostics and treatment of radiation-induced angiosarcoma in the patient with multiple primary synchronous lesions of the breast and bladder.

Rectal cancer (RC) is one of the leading tumor location in the structure of the incidence of malignant neoplasms in the Russian Federation and the world. And the standard approach to the treatment of patients with locally advanced forms of RC is preoperative chemo-radiotherapy (CRT) with delayed surgery. The use of such sort of approach in the recent decades has led to the reduction of the frequency of local recurrence up to 10% and even less. However, approximately a third of patients die of distant metastases. In this regard, one of the main tasks in the treatment of patients with locally advanced forms of RC with adverse prognostic factors is the prevention of distant metastasis formation. Early initiation of the systemic therapy before surgery is aimed at solving this issue. Conducting neoadjuvant chemotherapy (NCT) instead of CRT in RC treatment allows to avoid radiation reactions and injuries, occurring in some patients. Two-component oxaliplatin-containing regimens are the most well studied types of NCT in the treatment of patients with non-metastatic RC. In this connection, despite the differences in the treatment regimens and the number of cycles, a good tolerability of the method as well as no effect on the frequency of postoperative complications and in general a satisfactory results comparable to the effects of CRT were observed. The use of NCT in combination with targeted treatment modalities as well as three-component chemotherapy regimens are promising and encouraging treatment options for patients with RC with adverse prognostic factors.

This publication is the Russian translation of the Plain Language Summary (PLS) of the Cochrane Systematic Review: Grobbee EJ, Wisse PHA, Schreuders EH, van Roon A, van Dam L, Zauber AG, Lansdorp-Vogelaar I, Bramer W, Berhane S, Deeks JJ, Steyerberg EW, van Leerdam ME, Spaander MCW, Kuipers EJ. Guaiac-based faecal occult blood tests versus faecal immunochemical tests for colorectal cancer screening in average-risk individuals. Cochrane Database Syst Rev. 2022;6(6):CD009276. DOI: 10.1002/14651858.CD009276.pub2