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Background: Tumor infiltrating lymphocytes (TILs) are a promising inexpensive prognostic and predictive biomarker in breast cancer. High levels of TILs are associated with improved survival and higher probability to achieve pathological complete response in triple-negative breast cancer (TNBC)., Objective: To assess the level of TILs in TNBC samples and analyze the association between the level of TILs and the main pathological parameters, to identify their impact on long-term results., Material and Methods: The study included information on 140 patients with I-III stage TNBC and estrogen receptors <10%. Tumor tissue samples at baseline biopsies were evaluated the histological type, HER2 expression, estrogen expression levels, Ki-67 and TILs. The pathological response was evaluated according to the ypTNM, Miller-Payne, and RCB classifications., Results: The average level of TILs in biopsy specimens before NACT was 29.3±23.1%. Low levels of TILs (<10%) were defined in 21% of cases, intermediate levels (≥10% to ≤40%) in 55% of cases, and high levels (>40%) in 24% of cases. Using the two-tiered system, low TILs (≤40%) were defined in 76% and high TILs (>40%) in 24% of cases. The level of TILs was correlated with histological grade (R=0.187; p =0.027) and estrogen receptor expression level (R=0.211; p =0.012). There were no significant differences depending on the level of TILs and other pathological parameters. Three-year event-free survival (EFS) in patients with high TILs levels was 95% versus 65% in the low TILs group ( p =0.037)., Conclusion: Stromal TILs are an important prognostic biomarker in TNBC. Using a cutoff of 40%, high TILs are significantly associated with longer EFS.

Background: Diffuse large B-cell lymphoma (DLBCL) is the most common (30%-35%) type of B-cell lymphoma. Only about 60% of all newly diagnosed advanced-stage DLBCL can be completely treated with x6 R-CHOP. High-dose chemotherapy (HDCT) followed by autologous hematopoietic stem cell transplantation in the first remission (upfront auto-HSCT) can serve as an option to improve a prognosis in these patients., Aims: This trial aimed to improve prognosis in DLBCL by upfront auto-HSCT., Methods and Results: A group of 105 patients: DLBCL NOS, age 18-65, stage IV, IPI ≥2, CR/PR after x6 R-CHOP/DA-EPOCH-R from 2010 to 2019 at NMRC of Oncology named after N.N.Petrov of MoH of Russia was retrospectively analyzed. The HSCT group included patients with upfront HDCT followed by auto-HSCT (n = 35). The control group included patients with non-invasive follow-up after induction (n = 70). Primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), response rate and relapse rate. The 3-year OS (p = .013) and 3-year PFS (p = .033) were significantly higher in the HSCT group. The 3-year OS was decreased by the occurrence of relapse (p ≤ .001) and weight loss (B-symptom) (p = .04). DEL was the negative prognostic factor for 3-year PFS in all patients (p = .001) and control group (p = .001). DA-EPOCH-R significantly increased the 3-year PFS (p = .041)., Conclusion: Upfront HDCT followed by auto-HSCT can increase 3-year OS and PFS and improve prognosis in DLBCL NOS, age 18-65, stage IV, IPI ≥2 patients., (© 2023 The Authors. Cancer Reports published by Wiley Periodicals LLC.)

The concept of the personalized rehabilitation is based on the principle of applying physical and rehabilitative medicine techniques depending on the factors that mostly influence on rehabilitation efficacy in a particular patient - determinant of effectiveness. Current achievements in the diagnosis and treatment of breast cancer (BC) significantly increased overall patients' life expectancy, updating rehabilitative treatment stage, which is often unmet., Objective: To perform the comprehensive analysis of the efficacy of personalized rehabilitation programs in patients with BC., Material and Methods: The combined comparative multi-centre randomised trial of rehabilitation program efficacy in patients with breast cancer was done. The study included 219 patients aged from 30 to 45 years (median 39.4 year), who were divided into 2 groups. The rehabilitation by programs, that included current personalized rehabilitative techniques (RT) with proved efficiency, based on scientometrical analysis of evidential research was performed in the first group patients. In the second group aftercare was done according to the standard programs. The comprehensive evaluation of treatment efficacy was conducted in several stages: 1) performance analysis of rehabilitative programs; 2) verification of the effectiveness' determinant of rehabilitation; 3) factor analysis to assess the mechanisms of therapeutic effects in experimental groups; 4) comparative analysis of alternative strategies for selecting rehabilitation programs., Results: The use of rehabilitative programs, based on recommended RT, changes the rehabilitation structure, significantly increasing its efficacy by 17%. Furthermore, the percentage of high-efficiency usage of this type programs increases by 17% compared with standard programs. The main determinants, affecting the efficacy of rehabilitation programs, based on selected RT, are anamnestic data, parameters of exercise tolerance and physical activity and ultrasound parameters of upper limb blood flow. The therapeutic effects of personalized rehabilitation programs are realized by correction of clinical rates, increasing exercise tolerance and physical activity, as well as psychophysiological parameters., Conclusion: The use of the evaluation system of anamnestic, clinical, functional and psychophysiological features of patient (the effectiveness' determinant) in realization of personalized rehabilitation programs for women with BC, allows to predict and manage the efficacy of RT applying.

Eyelid tumors are the most common neoplasms in everyday ophthalmic practice and cover a wide range of benign and malignant lesions. Surgical methods, cryodestruction, laser therapy and radiation therapy are used in the treatment of malignant eyelid tumors. Chemotherapy does not occupy a prominent place in the treatment of malignant eyelid tumors, its use is limited to sensitive tumors., Objective: To assess the antitumor activity of the Russian-developed chemical compound 2-[3-(2-chloroethyl)-3-nitrosoureido]-1.3-propandiol (chlonisol) on the models of transplantable tumors of various histogenesis implanted into the lower eyelid., Material and Methods: The study was carried out on 67 mice of lines 129/SN, BALB/c and C57BL/6 that had Ehrlich carcinoma, sarcoma 37, lymphosarcoma LIO-1 and B16 melanoma transplanted into the eyelid. Tumor transplantation was done by injecting 0.05 ml of sterile sodium chloride solution containing 10 6 cells of Ehrlich carcinoma, sarcoma 37, lymphosarcoma LIO-1, or 10% suspension of tumor tissue of B16 melanoma. The injection was performed into the right lower eyelid in the direction from the outer towards the inner corner of the eye using a thin needle (29G). Chlonisol was administered at the maximum tolerated dose of 20 mg/kg or at the lower dose of 15 mg/kg intraperitoneally 24 hours after tumor transplantation., Results: In mice with Ehrlich carcinoma, sarcoma 37, lymphosarcoma LIO-1 and melanoma B16 transplanted under the skin of the lower eyelid, a single intraperitoneal injection of chlonisol at the dose of 20 or 15 mg/kg caused significant inhibition of tumor growth reaching 100%. Chlonisol significantly increased overall survival in animals with Ehrlich carcinoma (log rank test, p =0.0464), sarcoma 37 (log rank test, p <0.0001), lymphosarcoma LIO-1 (log rank test, p =0.0122) and B16 melanoma (log rank test, p <0.0001); the proportion of animals that were fully healed was 25, 78, 67 and 25%, respectively., Conclusion: Chlonisol has a pronounced antitumor effect in mice with Ehrlich carcinoma, sarcoma 37, lymphosarcoma LIO-1 and B16 melanoma transplanted into the eyelid.

Lessons Learned: Melatonin did not increase the efficacy of systemic chemotherapy in melanoma. Metformin did not increase the efficacy of systemic chemotherapy in melanoma., Background: Current data support the possibility of antitumor activity of melatonin and metformin., Methods: From March 2014 to December 2016, 57 patients with disseminated melanoma received dacarbazine (DTIC) 1,000 mg/m 2 on day 1 of a 28-day cycle, either as monotherapy (first group) or in combination with melatonin 3 mg p.o. daily (second group) or metformin 850 mg two times a day p.o. daily (third group) as the first-line of chemotherapy. The primary endpoint was objective response rate (ORR). Secondary endpoints were time to progression (TTP), overall survival (OS), immunologic biomarkers, and quality of life., Results: ORR was 7% and did not differ among the treatment groups. Median TTP was 57, 57, and 47 days, respectively, in the first, second, and third groups (р = .362). Median OS was 236, 422, and 419 days, respectively (p = .712). Two patients from the combinations groups showed delayed response to therapy. The increase of CD3 + CD4 + HLA-DR + lymphocytes (p = .003), CD3 + CD8 + HLA-DR + (p = .045), CD3 + CD8 + lymphocytes (p = .012), CD4 + CD25 high CD127 low lymphocytes (p = .029), and overall quantity of lymphocytes (p = .021) was observed in patients with clinical benefit., Conclusion: No benefit was found in either combination over DTIC monotherapy. Delayed responses in melatonin and metformin combination groups were registered. The increase of lymphocyte subpopulations responsible for antitumor immune response demonstrates the immune system's potential involvement in clinical activity., (© AlphaMed Press; the data published online to support this summary is the property of the authors.)

Gemcitabine is quite effective in the treatment of brain tumors, although this drug has a limited ability to overcome the blood-brain barrier (BBB). Aim of study is to assess the therapeutic efficacy of gemcitabine and other drugs with different permeability of BBB in the model of intracranial tumor. The therapeutic activity of gemcitabine, carmustine, cyclophosphamide and cisplatin was studied in mice with intracranially implanted Ehrlich tumor, and also gemcitabine in various doses - with intramuscularly implanted tumor. On intracranial tumor model gemcitabine (25 mg/kg) increased the life span (ILS) by 60-89% (p<0.001), despite the fact that its permeability of the BBB is about 10%. Therapeutic activity of carmustine, cyclophosphamide and cisplatin (ILS were 44, 22 and 11%, respectively) corresponds with the BBB permeability for these drugs (90, 20 and 8%, respectively). On intramuscular tumor model, gemcitabine showed significant antitumor effect at both 25 and 2.5 mg/kg, indicating a wide range of therapeutic doses of this drug. Pronounced therapeutic effect of gemcitabine on intracranial tumor most likely is due to the small but sufficient concentration of the drug that overcomes the BBB., Competing Interests: The authors declare that there is no conflict of interest., (© Georg Thieme Verlag KG Stuttgart · New York.)

Modern approaches to the organization of diagnosis and treatment of elderly and senile patients with malignant tumors allow to maintain the necessary level of health, improve the quality of life and increase life expectancy. Assessment of geriatric status in Oncology allows: to predict complications during the complex treatment, including drug treatment; to modify treatment to reduce the risk factors of adverse outcomes; to select patients for specialized treatment using standard schemes. So, timely assessment of geriatric syndromes and their correction can expand the indications for specialized treatment of elderly and senile patients.

HER2-positive breast tumors are found in 25-30% of patients with breast cancer and are characterized by aggressive course and reduced sensitivity to both chemotherapy and hormone therapy. The aim of the work was to study the possibilities of enhancing the therapeutic effect of anti-estrogen drug toremifene by combining it with biguanide, metformin, on the HER2-positive breast cancer model in FVB/N HER-2/neu transgenic mouse. Male FBV/N mice with intramuscularly transplanted HER2-positive mammary gland tumor from a female mouse of the same strain have been given toremifene (30 mg/kg, orally daily) or metformin (100 mg/kg, orally daily) that had a moderate antitumor effect (decrease the area under the kinetic curve of tumor growth by 1.6 and 1.5 times, respectively, when compared with intact control). Co-administration of these drugs in the same doses had a more pronounced effect (the area under the kinetic curve of tumor growth decreased by 3.1 times compared to intact control; p<0.05). After 10 days, in group receiving toremifene all 10 mice developed inguinal-scrotal hernias, and in group that received toremifene plus metformin - only 5 of 10 (p=0.0325). By the 15 th day after the start of treatment, the hernias was also determined in all mice treated with the combination of toremifene and metformin, but the size of the hernial sac was significantly smaller than in those receiving only toremifene - 537 ± 96 mm 3 and 1309 ± 120 mm 3 , respectively (p=0.0001). A possible explanation is the manifestation of collagen-degrading effect of toremifene., Competing Interests: The authors declare that there is no conflict of interest., (© Georg Thieme Verlag KG Stuttgart · New York.)

A combined antitumor effect of a single injection of doxorubicin and the indole hormone melatonin was investigated in the model of transplantable Ehrlich carcinoma in female SHR mice. Animals received melatonin either subcutaneous 10 mg/ kg in the evening or with water 10 mg/l at night (from 20 pm to 8 am) for 3 weeks. The results of an experiment showed that combined use of doxorubicin and melatonin both subcutaneous and with water leads to statistically significant inhibition of tumor growth compared with control and doxorubicin alone.

The aim of the study was to assess efficacy and safety of combined therapy with dacarbazine and melatonin or metformin in comparison with dacarbazine alone in the 1st line of therapy of cutaneous melanoma. Thirty-six patients with disseminated melanoma, therapy naïve, were included between March 2014 and December 2015. Patients received DTIC 1000 mg/m2 in day 1 of 28-day cycle either as monotherapy (group 1) or in combination with melatonin 3 mg PO daily (group 2) or metformin 850 mg 2 times a day PO daily (group 3). Thirty-four patients were randomized (15-in group 1, 8 - in group 2, 13 - in group 3) and received 119 cycles of therapy. Response rate was 11% in groups 1 and 2, and 8,3% - in group 3 (p=0,57). Median time to progression was 52, 79 and 63 days, respectively in the 1st, 2nd and 3rd group (р=0,468). Two patients from the 2nd and 3rd group showed delayed response to therapy. No adverse events of grade 3-4 were seen. Thus, DTIC with melatonin or metformin was well tolerated. No meaningful increase of adverse event incidence was seen. No benefit of either combination was shown in this interim analysis. Delayed responses in melatonin and metformin combination groups were registered. This suggests immunologic effect of both drugs and warrants further study.

Using of radiochemotherapy improves short-term and long-term results of treatment in patients with primary Hodgkin’s lymphoma (HL) comparing with treatment by chemotherapy alone. The rates of 5-year, 10-year OS and DFS are 88%, 83% and 90%, 86% in case of radiochemotherapy, versus 73%, 66% and 72%, 68% using chemotherapy alone. The 5-year and 10-year OS, DFS estimates in treatment with ABVD are 84% and 83%, 75% and 74%; BEACOPP-baseline - 83% and 82%, 82% and 81% (p<0.05). At the same time ABVD chemotherapy develops less toxicity (p<0.001). The treatment with 6 cycles of ABVD is considered as the most appropriate in primary Hodgkin’s lymphoma patients with extranodal lesions. Comparison of complications rate during chemotherapy with MOPP, ABVD, BEACOPP-baseline, BEACOPP-escalated reveals major hematologic toxicity and infectious complications rate in BEACOPP-escalated program (p<0,05). The age ≥45 years, hemoglobin <105g/l, B symptoms, fibrinogen >5g/l, involvement of 3 and more areas of lymph nodes, liver involvement, inguinal lymph nodes are defined by the multiple-factor analysis as adverse prognostic factors of patients with primary Hodgkin’s lymphoma (HL) with extranodal lesions (p<0.05). Allocation of group of high risk is proved by correlation between survival and the Prognostic Score (PS). The 5-year and 10-year DFS, OS for patients with PS-0-2 estimates are 88% and 86%, 89% and 83%, for patients with PS-3-4 - 78% and 69%, 80% and 77%, for patients with PS-5-6 - 43% and 42%, 60% and 38% respectively (p<0.001).

The aim of this study was to create a multi-dimensional correlation matrix of determinants giving information on the degree of influence on survival of young adults with Hodgkin’s lymphoma each variable as well as the effect of the interaction of these variables with each other. 87 patients with Hodgkin’s lymphoma at the age of 19 to 29 years (mean age 24 ± 4 years) were included in the study. Multiple matrix containing the coefficients of correlation of survival and correlation coefficients of 35 analyzed factors was of 5 significant determinants (volume of tumor lesion, stage IV of disease, E-damage, accelerated erythrocyte sedimentation rate, leukocytosis). Construction of the correlation matrix in order to select factors to be included in the equation, which contained the pair correlation coefficients of overall survival and each of factors, showed that only the volume of tumor lesion (correlation coefficient 0.2570, p = 0.026) influences on sign-result. Multiple regression equation is represented as follows ȳ=0,166667-0,227273x[volume]; R2=0,0643674507. This equation allows for given values of the factor «volume of tumor lesion” to have theoretical values of resultant sign (survival), substituting the actual values of the factor in it.

Gemcitabine is known to exert a therapeutic effect on brain tumors despite the limited permeability of the blood-brain barrier (BBB). In our experimental research single intraperitoneal (i.p.) injection of gemcitabine 25 mg/kg provided increase in median survival of mice with intracranially transplanted Ehrlich carcinoma by 41-89% (p < 0.001). In this experimental model i.p. administration of gemcitabine (permeability of the BBB of less than 10%), carmustine (good permeability of the BBB), cyclophosphamide (poor permeability of the BBB) and cisplatin (doesn't penetrate through the BBB) increased median survival of mice by 88% (p < 0.001), 59% (p = 0.001), 35% (p = 0.005) and 18% (p = 0.302) respectively. Considering strong correlation between antitumor activity of the drugs (carmustine, cyclophosphamide and cisplatin) and their permeability of the BBB, efficacy of gemcitabine in intracranial tumors could be due to its wide range of therapeutic doses.

In the randomized phase 2 study there was evaluated the efficacy of neoadjuvant endocrine treatment (anastrozole, exemestane) in comparison with chemotherapy (doxorubicin plus paclitaxel). Preoperative endocrine therapy was well tolerated. There was a trend towards higher overall rates of objective response and breast conserving surgery (BCS) among patients with tumors expressing high levels of ER (luminal A) in endocrine therapy group compared with chemotherapy group (43% vs 24%; p = 0,054). In HER2-positive breast cancer patients the addition of trastuzumab to neoadjuvant chemotherapy improved the overall and pathological complete response. Trastuzumab made possible an increasing number of breast conserving surgery (23% vs 13%; p = 0,022). No patient treated with trastuzumab and with chemotherapy had a local recurrence after BCS.

Cancer stem cells (CSCs) possess self-renewal and heterogeneous cancer cell lines formation. Numerous data confirm the existence of a model in which CSCs have an important role in cancer initiation, progression and clinical outcome. Analysis of CSCs role in metastasis, in contrast, remains mainly conceptual and hypothetical. Recent data are summarized in this review which support the CSCs theory as a source of breast cancer metastatic lesions with noting the key role of the microenvironment.

The purpose of this study was to establish the role of scintimammography with 99mTs-technetril for predicting pathological status of regional lymph nodes after neoadjuvant chemotherapy. In 123 primary patients with locally advanced breast cancer stage cT1-4N0-3M0 there was performed scintimammography: before treatment and after 2-3 cycles of neoadjuvant chemotherapy 63 patients; after 2-3 cycles of neoadjuvant chemotherapy and before surgery--in 5 patients; after 4-6 cycles of neoadjuvant chemotherapy--55 women. All patients were divided into 2 groups: the first included 68 patients whom scintimammography was performed before and after 2-3 cycles of neoadjuvant chemotherapy; the second--60 women whom scintimammography was performed before treatment and before surgery. In patients of the first group positive results were obtained in 16 (23.5%), negative--26 (38.3%), false positive--16 (23.5%) and false negative--10 (14.7%) cases. Sensitivity, specificity, overall accuracy, positive predictive value and negative results were 61.5%, 61.9%, 61.7%, 50% and 72.2%, respectively. During the scintimammography after 4-6 cycles of neoadjuvant chemotherapy positive results were observed in 17 (28.3%) negative--18 (30%), false positive--19 (31.7%) and false negative--6 (10%) of patients. Thus, the sensitivity, specificity, overall accuracy, positive predictive value and negative results amounted to 73.9%, 48.6%, 58.3%, 47.2%, 75% respectively.

Endogenous intoxication and immune insufficiency accompany neoplastic process. Complex therapy for cancer worsens these pathologic conditions by its adverse effects (AE) and thus complicates treatment. Efferent therapy can provide continuity of antineoplastic therapy with normalization of hemostasis and decreasing the rate of AE and their intensity. Efferent therapy meaningfully increases patient's quality of life and decreases the needed drug support when used as a part of complex therapy. Proper use of efferent therapy can markedly increase efficacy of surgical treatment, radiation therapy and drug therapy.

Rehabilitation of a cancer patient should be aimed not only at eliminating the disease itself and restore natural functions of the body but also at the maximum acceptable recovery of the human abilities to live with the disease and after it. Rehabilitation is carried out by efforts various professionals who in their work should take into account the state of a cancer patient and the features of his personality. Rehabilitation is one of factors in improving the quality of life of cancer patients.

Breast carcinomas caused by inheritance of cancer-predisposing germ-line mutations have specific bioclinical features. This study aimed to analyze the efficacy of conventional cytotoxic treatment in BRCA1 and CHEK2 mutation carriers and non-carriers. The study included 415 Russian breast cancer patients aged 50 years or younger, who were subjected to various standard schemes of neoadjuvant therapy. The choice of therapy was done without the knowledge of the mutations status, because DNA testing was performed retrospectively using the archival tissue samples. 19 BRCA1 (4.6%) and 8 CHEK2 (1.9%) heterozygous genotypes were identified. BRCA1 mutation carriers achieved pathological complete response more frequently than non-carriers [6/19 (31.6%) vs. 46/388 (11.9%), p = 0.024]; this effect was limited to women treated by anthracycline-based therapy without taxanes [5/9 (55.6%) vs. 28/247 (11.3%), p = 0.002] and was not observed in any of 7 BRCA1 carriers receiving taxane-containing regimens. CHEK2 heterozygotes did not experience pathological complete response and showed lower frequency of objective clinical responses as compared to mutation non-carriers [4/8 (50%) vs. 333/388 (85.5%), p = 0.020]; the efficacy of neoadjuvant therapy was particularly poor in CHEK2 carriers receiving anthracyclines without taxanes. This study provides evidence for distinct sensitivity of BRCA1 and CHEK2 mutation-driven breast carcinomas to standard chemotherapeutic schemes.