Mutations in the BRCA1/2 genes are oncogenic, since their carriers are associated with an increased risk of developing malignant neoplasms of the mammary glands, ovaries, fallopian tubes, peritoneum, as well as breast cancer in men and, less often, pancreatic cancer. When oncogenic mutations are detected, the information obtained should be used in the formulation of personal recommendations on possible effective lifestyle measures and modifications to reduce the predicted cancer risks. The article contains data from the European Society of Medical Oncology (ESMO), including an indication of the strength of the recommended measures. To manage these risks, timely risk-reducing salpingo-oovarectomy, risk-reducing mastectomy, as well as annual selective screening of diseases of the mammary glands, ovaries and, if indicated, other organs are recommended, informing the patient about the risks at the time of treatment and personalized strategies aimed at reducing them.
Aim. To compare the efficacy and toxicity of regorafenib therapy and the repeated use of anti-EGFR monoclonal antibodies (mAb) combined with chemotherapy (CT) in the third-line treatment of patients with left-sided metastatic colorectal cancer (mCRC) with wild-type RAS and BRAF genes who received anti-EGFR targeted therapy in the first line of treatment. Materials and methods. The database of patients with mCRC from 5 clinics in the Russian Federation was retrospectively analyzed. The study had 3 arms depending on the third-line therapy: regorafenib, reintroduction and rechallenge with the combination of CT and anti-EGFR mAb. In this paper, we present data comparing reintroduction and regorafenib therapy. Results. 132 patients with morphologically confirmed left-sided mCRC with wild-type RAS and BRAF genes who received at least 3 lines of drug therapy from 2014 to 2023 were identified: the first-line therapy included anti-EGFR mAb; 61 patients were reintroduced with a combination of CT with anti-EGFR mAb, and 71 patients received regorafenib in the third-line therapy. Disease control in the reintroduction group was achieved in 43 (70.5%) patients, compared with 18 (25.5%) in the regorafenib group (p = 0.0001). The six-month overall survival (OS) was 76% in the reintroduction group and 55% in the regorafenib group. The median OS in the reintroduction group was 18 months (95% confidence interval [CI] 11.9-24.0 months) and 10 months in the regorafenib group (95% CI 5.3-14.6 months; p = 0.05 according to the log-rank test; p = 0.013 according to the Breslow-Wilcoxon test; p = 0.024 according to the Tarone-Ware test; risk ratio 1.1, 95% CI 0.886-1.408; p = 0.349). Progression-free survival (PFS) was higher in the CT reintroduction group with anti-EGFR mAb (6 months [95% CI 5.3-6.6 months] than in the regorafenib group (3 months [95% CI 2.2-3.7 months]; p = 0.0001 according to the log-rank test, risk ratio 1.23, 95% CI 0.997-1.529; p = 0.053). We found no difference in the incidence of all-grade adverse events between the study groups (p = 0.19), nor in the incidence of grade 3-4 adverse events (p = 0.781). Conclusion. Compared with regorafenib therapy, re-administration of a combination of CT with anti-EGFR targeted therapy in the third-line treatment of patients with left-sided mCRC with wild-type RAS and BRAF genes was associated with a higher rate of disease control and better PFS and 6-month OS.
Background. The risk of second primary malignancies in prostate cancer (PC) is increasing due to the increase in life expectancy and the widespread use of advanced imaging techniques. Increased expression of the prostate-specific membrane antigen (PSMA) ligand in gastrointestinal tumors enables detection on positron emission tomography combined with computed tomography (PET/CT). Aim. To assess the diagnostic performance of PET/CT with 18F-PSMA-1007 in the detection of gastric cancer (GC) in patients with PC and the correlation of tumor metabolism with clinical parameters. Materials and methods. The results of PET/CT with 18F-PSMA-1007 were retrospectively analyzed in 520 patients with histologically confirmed stage I–IV PC during primary staging, assessment of the therapeutic effect, and follow-up. The imaging was performed using a combined GE Discovery PET/CT 710 system. SUVmax was correlated with some clinical parameters. Results. GC as a primary tumor was detected in 7 of 520 (1.3%) patients aged 65 to 77 years, with a median of 73 years. The diagnosis was established endoscopically, histologically, and immunohistochemically to exclude metastatic disease. Adenocarcinomas of various degrees of differentiation prevailed: poorly differentiated (n = 4), moderately differentiated (n = 2), and well-differentiated (n = 1). In 5 patients, the tumor was located in the body of the stomach, and in 2, in the antrum. Depending on the time of GC detection after diagnosis of PC, synchronous tumors were diagnosed in 3 (42.9%) cases, and metachronous tumors in 4 (57.1%). The latency period ranged from 4 to 99 months, with a mean of 36.8 months. Semiotics of GC according to PET/CT is represented by diffuse hyperuptake of the radiopharmaceutical in the walls, with thickening of the mucous membrane from 18 to 30 mm, with a mean of 22.14 mm, up to 75 mm. The SUVmax coefficient ranged from 8.79 to 34.57, with a mean of 21.45. In synchronous tumors, the median SUVmax was 27.74, in metachronous tumors, 18.04. A significant positive correlation (r = 0.56) between SUVmax and the T index was found. Conclusion. The presence of second tumors, including GC, in patients with PC is a challenging differential diagnostic problem. PET/CT with 18F-PSMA-1007 enables the timely detection of such neoplasms in 1.3% of cases at both therapeutic and diagnostic stages.
Background. Surgery is the primary treatment modality for non-metastatic colorectal cancer (CRC), required in approximately 88% of cases, either as monotherapy or in combination with adjunct therapies. Precise colon resection is essential for optimizing both immediate and long-term outcomes. Several clinical studies have shown that robotic technology reduces intraoperative blood loss and conversion rates. Objective. To evaluate the early experience with the Da Vinci Xi robotic system for the treatment of CRC at Oncology Centre No. 1, Moscow City Clinical Hospital named after S.S. Yudin. Materials and methods. Treatment outcomes were retrospectively analyzed in 157 patients with localized CRC who underwent robotic surgery between August 2024 and December 2025. Results. Conversion to open surgery was necessary in two cases due to large tumor size and injury to the main artery. The duration of surgery ranged from 110 to 767 minutes, with a median of 265 minutes. Intraoperative blood loss ranged from 50 to 400 mL, with a median of 50 mL. Postoperative hospital stay ranged from 4 to 48 days, with a median of 7 days. A total of 67 patients (43%) required transfer to the intensive care unit after surgery. Conclusion. The initial experience at this center demonstrates the feasibility of rapid and effective adoption of the Da Vinci Xi robotic system in colorectal surgery, with acceptable immediate outcomes for localized CRC, provided the operator has sufficient experience in minimally invasive CRC surgery.
Background. The DEFENDOR SPECIAL study (NCT04905329) evaluated the efficacy and safety of combination chemotherapy with empegfilgrastim for the primary prevention of neutropenia in patients with malignancies at high risk of recurrence. This article presents the results of an investigator-initiated analysis assessing the efficacy and safety of empegfilgrastim (Extimia®) in patients with stage II–III HER2-positive breast cancer (HER2+ BC) who received neoadjuvant therapy (NAT) with the TCHP regimen. Aim. To assess the clinical efficacy and safety of prolonged granulocyte colony-stimulating factor empegfilgrastim in patients with early HER2+ BCG treated with NAT as part of the TCHP regimen. Materials and methods. Data from 105 patients were analyzed. For the primary prevention of febrile neutropenia (FN), all patients received subcutaneous empegfilgrastim at a dose of 7.5 mg once per course. The primary endpoint was the relative dose intensity of the NAT courses, and the secondary endpoints included the complete pathomorphologic regression (pCR) rate, residual cancer burden (RCB), and adverse event rate. Comparison of pCR rates in this study and in the external control group of patients with early HER2+ BC of the clinical stage cT2-cT4/cN0-cN3/cM0, who received NAT in the TCHP regimen with filgrastim for the FN prevention from April 2020 to September 2023 at the Loginov Moscow Clinical Scientific Center. The matching based on the initial characteristics was performed using complete matching with the Mahalanobis distance. Results. In the DEFENDOR SPECIAL study, the median age (Q1–Q3) was 53 (43–61) years. The median relative dose intensity (Q1–Q3) was 97.1% (76.8–104.9%). PCR was achieved in 72.5% (76/105) of patients, while RCB-I and RCB-II were observed in 6.6% (7/105) and 15.2% (16/105), respectively. The highest pCR rate was observed in patients with HR-negative/HER2-positive (3+) tumors at 85.3% (29/34). No FN events were reported. Grade III–IV neutropenia occurred in 2.9% (3/105) of patients, grade I–II thrombocytopenia in 34.3% (36/105), and grade III thrombocytopenia in 1.0% (1/105). The probability of achieving pCR with empegfilgrastim was statistically significantly higher compared to filgrastim, with an adjusted odds ratio of 1.73 (95% confidence interval 1.04–2.89; p = 0.0357). Conclusion. Primary prevention of FN with empegfilgrastim offers a significant advantage in achieving pCR compared to filgrastim in patients with early HER2-positive breast cancer receiving a neoadjuvant TCHP regimen.
Background. Interest in combined treatment modalities for signet ring cell carcinoma and other subtypes of poorly cohesive gastric carcinoma has increased in recent years. Objective. To study and compare the effectiveness of two approaches to the treatment of poorly cohesive carcinoma: perioperative chemotherapy (CT) and surgery at the initial stage. Materials and methods. A total of 112 patients with poorly cohesive gastric carcinoma were included. Of these, 40 patients treated between 2018 and 2023 received perioperative chemotherapy with FLOT or mFOLFIRINOX. The historical control group comprised 72 patients treated between 2015 and 2018 who underwent initial surgery, followed by adjuvant XELOX chemotherapy in cases of pT ≥ 2 and pN+. In both groups, the diagnosis of poorly cohesive gastric carcinoma was confirmed by histological slide review of surgical specimens. Results. The five-year overall survival (OS) rate was 56.8% in the perioperative chemotherapy group and 50.8% in the surgical treatment group. Although survival rates favored perioperative treatment, the difference was not statistically significant (Log-Rank test; p = 0.073). The median OS in the surgery group was 67 months, while it was not reached in the perioperative chemotherapy group. Patients in the surgical treatment group presented with more advanced tumor stages, which may have contributed to the observed OS differences. Stage-specific analysis revealed no significant differences in OS between groups at any stage. Univariate Cox regression analysis indicated a trend toward treatment affecting OS (p = 0.081), but multivariate regression identified TNM stage as the only significant predictor of OS. Perioperative chemotherapy was not an independent prognostic factor. No differences in three-year OS were observed among patients with different tumor grades, regardless of perioperative chemotherapy regimen. In the FLOT and FOLFIRINOX groups, the three-year OS rates were 77.7% and 80.5%, respectively (Log-Rank test; p = 0.44). The median OS in the FOLFIRINOX group was 49.7 months, while it was not reached in the FLOT group. Conclusion. The lack of significant differences in survival prevents a definitive conclusion regarding the superiority of perioperative chemotherapy compared to initial surgery in patients with poorly cohesive gastric carcinoma. Further investigation in randomized controlled trials is warranted.
The treatment of metastatic HR+ Her2neu negative breast cancer (BC) is a challenging clinical task that required in-depth study of oncogenesis and the development of several new classes of drugs, which significantly changed the therapeutic arsenal. The results of the MONALEESA-2, -3, and -7 studies demonstrated the efficacy of the combination of ribociclib with endocrine therapy in this cohort of patients, leading to clinically and statistically significant increases in progression-free and overall survival, including in patients with adverse prognostic factors. The results of real-world clinical practice were no less optimistic, as demonstrated by the presented clinical cases. The paper presents three clinical cases of patients with metastatic HR+/HER2- BC in whom ribociclib-based combination therapy provided an unusually long control of the disease. Clinical case 1. A 42-year-old female patient with luminal B HER2- BC and multiple bone metastases received ribociclib in combination with letrozole after ovariectomy. During therapy, a complete metabolic response was achieved, which persisted for more than 97 months. The adverse events were limited to a manageable grade 1 arrhythmia and a neutropenia episode. Clinical case 2. A 70-year-old female patient with late recurrence of BC and metastatic lesions of lymph nodes and bones received ribociclib in combination with letrozole in first-line therapy. Sustained regression of lymphadenopathy and stabilization of bone lesions with a disease control duration of 72 months were achieved. No toxicity was reported, and no dose reduction was required. Clinical case 3. A 64-year-old female patient with visceral and bone metastases and a PIK3CA mutation received ribociclib + fulvestrant in the second-line therapy. Long-term stabilization was achieved within 6.5 years with minimal toxicity. Progression required a change in therapy regimen. The presented cases demonstrate the possibility of long-term control of metastatic HR+/HER2- BC with ribociclib in combination with endocrine therapy, confirming the importance of molecular-specific therapy selection and the potential of an individualized approach in clinical practice.
Background. Robot-assisted gastric cancer surgery has achieved outcomes comparable to laparoscopic interventions and demonstrates specific technical advantages. Several studies report similar results among robotic-assisted, laparoscopic, and open procedures for gastric cancer. Nevertheless, additional data are required to draw definitive conclusions. This study presents the technical aspects of robot-assisted gastrectomies (RAGs) following neoadjuvant chemotherapy (NACT), based on the largest single-center experience with these procedures in Russia. Aim. To demonstrate the technical feasibility and safety of performing RAGs using the Da Vinci Si surgical robot system in patients with locally advanced gastric cancer after NACT, and to propose a standardized RAG technique for implementation in clinical practice. Materials and methods. To date, 96 RAGs have been performed using the Da Vinci Si surgical robot system after NACT in patients with locally advanced gastric cancer, as part of an ongoing prospective study comparing RAG outcomes with those of laparoscopic gastrectomies (LGE). The study aims to enroll 250 patients, divided into two groups: Group 1 (test) includes patients who undergo RAG, and Group 2 (control) includes patients who undergo LGE. Randomization is conducted using the envelope method. Results will be published as the data collection and analysis progress. Results. No intraoperative complications or access conversions were observed in the patient cohort. Early postoperative complications occurred in 7.3% of patients; in one case (1%), a repeat laparoscopic intervention was necessary. There was one death (1%). Conclusion. RAG in patients with gastric cancer following NACT is a technically feasible and safe surgical intervention. The described RAG technique is ergonomic and may serve as a methodological reference for surgical practice.
Background. Adrenocortical carcinoma (ACC) is a rare malignancy characterized by aggressive behavior and poor prognosis. Radical resection remains the only curative treatment, yet locally advanced disease with invasion of adjacent organs and major vessels frequently necessitates combined and multiorgan resections. Evaluating the outcomes and safety of such aggressive surgical approaches is essential to refine treatment strategies and indications. Aim. To evaluate the outcomes and prognostic factors of combined resections in patients with stage III–IV adrenocortical carcinoma, including procedures with vascular and multiorgan involvement. Materials and methods. This retrospective study was conducted at the Blokhin National Medical Research Center of Oncology and included 192 patients with stage III–IV adrenocortical carcinoma who underwent surgery between 1987 and 2022. A detailed analysis was performed for 115 patients who underwent combined resections involving adjacent organs and/or major vessels. For comparison, data from 42 standard adrenalectomies and 13 exploratory interventions were analyzed; an additional group of 20 patients received non-surgical treatment. Survival was assessed using the Kaplan–Meier method, and independent prognostic factors were identified using Cox proportional hazards regression (p 0.05). Results. Among 115 patients who underwent combined resections, postoperative complications occurred in 55.6% versus 16.6% after standard operations (p = 0.0001); postoperative mortality rates were 11.4% and 2.4%, respectively. Radical (R0) resections were associated with significantly better survival: median overall survival reached 84 months versus 4 months after palliative procedures (p 0.01). In stage IV disease, the best outcomes were observed in patients who achieved R0 resection limited to the abdominal cavity (median 41 months), compared to 8 and 11 months after conditionally radical and R2 resections, respectively (p = 0.004). Multivariate analysis confirmed the prognostic significance of resection radicality as prognostic factor. Conclusion. Radical resection remains the key determinant of survival in patients with stage III–IV adrenocortical carcinoma. Our analysis confirms that combined surgical procedures, despite their technical complexity and higher risk of complications, are justified and provide a significant improvement in long-term outcomes for this patient population.
Background. Cytoreductive surgery is the mainstay of treatment for patients with advanced ovarian cancer (AOC). Bowel resection is often required to achieve complete cytoreductive surgery. However, such interventions are associated with an increased risk of postoperative complications, which may affect the timing of adjuvant chemotherapy and long-term oncological outcomes. Aim. To assess the frequency and structure of postoperative complications in patients with AOC who underwent cytoreductive surgery with bowel resection, and to analyze their impact on the timing of chemotherapy initiation, relapse-free and overall survival. Materials and methods. A retrospective study was conducted on 67 patients with stage IIB–IV ovarian cancer who underwent cytoreductive surgery, including bowel resection, at the Blokhin National Medical Research Center of Oncology from 2018 to 2023. The incidence of complications was assessed using the Clavien–Dindo classification. The impact of complications and timing of chemotherapy initiation on overall and relapse-free survival was studied using the Kaplan–Meier method with the Log-rank test. Results. Postoperative complications were registered in 10.4% of patients; severe (III–IV according to Clavien–Dindo) – in 6%. The median time before the start of chemotherapy was 21 days; in 42% of patients, treatment was started after 21 days. Relapse-free survival after 3 years was about 50%, the overall 5-year survival was 71%. Differences in relapse-free and overall survival between subgroups (with and without complications; with and without delayed chemotherapy) did not reach statistical significance (p 0.1), but there was a tendency for survival to decrease in the presence of complications. Conclusion. Bowel resection as part of operations for AOC provides an increase in the frequency of achieving complete and optimal cytoreduction with an acceptable complication rate. Despite some prolongation of the timing of the start of chemotherapy in case of complications, no statistically significant deterioration in long-term results was recorded. The data obtained confirm the justification of a more aggressive surgical approach with adequate postoperative management of patients.
Background. Over the past 10 to 15 years, robot-assisted esophageal resections have transitioned from an experimental technique to a significant component of surgical management for esophageal cancer. International experience has demonstrated that this approach achieves oncological outcomes comparable to those of open and conventional minimally invasive procedures, while also reducing postoperative complications. Aim. To evaluate the outcomes of surgical treatment for esophageal cancer using robot-assisted minimally invasive resections. Materials and methods. A retrospective analysis was conducted on 13 patients with intrathoracic esophageal cancer who underwent surgery between 2024 and 2025. All patients received Lewis and McKeown robot-assisted minimally invasive esophageal resections. The DaVinci Xi robotic platform was utilized during the thoracic stage in all cases. At the abdominal stage, both robotic and standard laparoscopic approaches were employed, with one patient requiring a laparotomy. Results. The mean duration of surgery was 424.2 ± 132.2 minutes (95% confidence interval: 344.2–504.1). Median intraoperative blood loss was 96.2 mL (interquartile range: 50–100). The median intensive care unit stay following surgery was 3 days (interquartile range: 1–2.5). Postoperatively, pneumonia was the most frequent complication, occurring in three patients (23%). The most severe complication was esophagogastric anastomosis dehiscence, observed in two patients (15%). In one case (7.7%), esophagogastric anastomosis dehiscence following Lewis surgery resulted in death. Conclusion. Robot-assisted resection for esophageal cancer represents an advanced and promising surgical approach that integrates oncological radicality with enhanced safety.
Published data suggest that rare (non-ABD-type) insertions in the NPM1 gene, regardless of other mutations and clinical factors, are associated with an unfavorable prognosis. Currently, more than 60 different insertions in exon 12 of the nucleophosmin gene have been identified in acute myeloid leukemia (AML). The article summarizes current information on the types of these mutations and presents two clinical cases of AML with new rare insertions in the NPM1 gene. In an additional molecular genetic study of recurrent mutations in the DNMT3A, NPM1, FLT3, IDH1, and IDH2 genes, in the first clinical case, a patient with AML had IDH1 р.R132C and a new, previously unreported mutation NPM1 р.W288Cfs*12, which corresponds to NM_002520.7(NPM1):c.863_864insTGCT(p.Trp288fs) in the HGVS nomenclature. The patient died from infectious and toxic complications in the second line of the remission induction therapy according to the "7+3" protocol. This clinical case demonstrates the failure of standard treatment, namely the failure to achieve complete remission after the first line of remission induction therapy, which is a significant factor in the poor long-term prognosis of AML and indicates the need to consider allogeneic hematopoietic stem cell transplantation. In the second clinical case, a patient with AML had FLT3-ITD c.612ins102b.p. and a new previously unreported mutation NPM1 p. W290Kfs*10, NM_002520.7(NPM1):c.868_869insAAGC(p.Trp290fs) according to the nomenclature of the Human Genome Variation Society (HGVS). This case is an illustrative example of the rapid achievement of long-term MRD-negative remission using a combination of targeted drugs, and also shows how understanding the molecular and genetic basis of the disease pathogenesis leads to the development of new drugs for targeted therapy of AML, increasing the effectiveness and capabilities of treatment of complex subgroups of patients, as well as allowing to obtain previously unattainable treatment outcomes.
Remote monitoring (RM) of patients involves the continuous or periodic monitoring of a patient’s condition outside the hospital, utilizing modern digital and telecommunication technologies. RM is actively integrated into oncology practice. Modern medical systems offer several basic methods of RM. Modern RM systems enable the real-time recording of various clinically significant complications, automatically notifying medical personnel of critical changes to promptly adjust therapy and reduce the need for emergency medical care. The purpose of the paper is to review the literature data on RM in patients with malignancies. We reviewed publications in the leading scientific databases (PubMed, Google Scholar, and the National Library of Medicine) over the past decade. Data on the most common commercial and applied systems with effectiveness confirmed in several studies and described in open sources are summarized. The characteristics of the included studies – follow-up periods, methods of data collection and analysis, as well as the organization of interaction between doctors and patients – differed significantly, covering periods from 3 to 12 months. The use of Navigating Cancer, ОНКОНЕТ, eRAPID, SCH, Kaiku Health, and other platforms reduced the rate of unscheduled hospitalizations from 32.5% to 20.0% (relative reduction ~38%) and increased patient adherence to therapy to 73–79% (and up to ~92% in the PRO-TECT protocol). According to Kaiku Health, the average response time of the doctor to an alarming event was 19.6 hours. The Russian ONCONET study noted a decrease in the incidence of complications of antitumor treatment, as well as the risk of postponing the dates of the next course of chemotherapy, which significantly improved patient survival. Symptom Care at HOME (PRO-TECT) automated data collection systems significantly improved symptom control and quality of life scores. RM technologies demonstrate convincing efficacy, reducing the need for emergency medical care, improving the control of complications, and, according to some studies, are associated with an increase in the overall survival of cancer patients. Their widespread introduction into the oncological care system is justified, provided that the standardized notification protocols, sustainable funding, and organizational support are available. However, the systematization of the available data presents a significant methodological challenge due to the lack of unified approaches in implementing RM projects, the heterogeneity of methods for assessing effectiveness, and the wide range of conditions and organizational models studied.
In the article «The reasons for prescribing antitumor drugs beyond the registered indications in real clinical practice: A retrospective study», published in the Journal of Modern Oncology, Vol. 26, No.4, 2024 (DOI: 10.26442/18151434.2024.4.203108), errors were made: The number of used medicinal products (MPs) was corrected in the sentence "The use of 47 MPs was reported, including 46 antitumor agents and drugs with antitumor activity as part of 73 antitumor drug therapy regimens". Correct wording of the sentence: "The use of 46 MPs as part of 73 antitumor drug therapy regimens was reported". The names of 3 drugs and 1 applied regimen in 4 rows of the table have been corrected. Table row: The correct version: 36 Palbociclib + fulvestrant Palbociclib 36 Palbociclib + fulvestrant Cyclophosphamide Table row: The correct version: 46 Docetaxel + carboplatin + trastuzumab Cyclophosphamide 46 Docetaxel + carboplatin + trastuzumab Calcium folinate Table row: The correct version: 47 Capecitabine + bevacizumab Calcium folinate 47 Capecitabine + bevacizumab – Table row: The correct version: 70 FOLFIRINOX + bevacizumab (oxaliplatin, irinotecan,calcium folinate, fluorouracil, bevacizumab) – 70 FOLFOXIRI + bevacizumab (oxaliplatin, irinotecan,calcium folinate, fluorouracil, bevacizumab) – The errors were corrected at the request of the authors' team. The publisher replaced the original version of the published article with the corrected one; the information on the website was also corrected. The publisher apologizes to readers and authors for the errors and is confident that the correction of errors will ensure the correct perception and interpretation of the results of the study described in the text.
Triple-negative breast cancer (TNBC) is the most unfavorable subtype of breast cancer. Achieving pathological complete responce (pCR) is an important prognostic factor in patients diagnosed with TNBC, as it is associated with increased overall and disease-free survival. Currently, clinical parameters and pathological examination of resection tissue after surgery are used to evaluate the effectiveness of neoadjuvant drug chemotherapy (NAC). Traditional clinical and instrumental methods used in routine practice (examination, palpation, ultrasound of the mammary glands and regional areas, mammography, and MRI of the mammary glands) often do not allow for an accurate assessment of the treatment effect. The rate of detection of complete responses may be lower with clinical and instrumental assessment of the effect compared to pathological examination. In this regard, there is growing interest in assessing the effect of NAC based on changes in circulating tumor DNA (ctDNA) levels in the blood, which is characterized by the presence of genetic alterations specific to tumor tissue, i.e., liquid biopsy. This study examines two clinical cases of TNBC, determining the dynamics of ctDNA level changes during treatment and comparing these results with the severity of pathological tumor responce after NAC. In one case, pathological complete responce was achieved, while in the second, significant residual tumor was detected. Mutations for tracking ctDNA level dynamics were selected based on bioinformatics analysis of whole-exome sequencing of tumor biopsy samples and patient’s blood. Plasma ctDNA levels were assessed using digital PCR (dPCR). We obtained quantitative results for ctDNA determination in the plasma of patients with TNBC at five points and compared the dynamics of ctDNA level changes with the results of NAC. The study discusses the possible relationship between the observed ctDNA dynamics and treatment response (achievement of complete pathological tumor regression) and the feasibility of using liquid biopsy in predicting tumor response to NAC.
Background. Recent clinical trials have demonstrated the potential efficacy of immune checkpoint inhibitors as monotherapy or in combination for the treatment of patients with advanced cervical cancer (CC). At the same time, the effectiveness and safety of this treatment approach in domestic clinical practice remain largely unexplored. Aim. To evaluate the efficacy and safety of immune checkpoint inhibitors in patients with advanced CC in real clinical practice. Materials and methods. From January 2018 to June 2023, a retrospective analysis of the efficacy and safety of pembrolizumab therapy was performed in 96 patients, all with histologically confirmed CC: squamous cell (n=81), adenocarcinoma (n=12) and adenosquamous cancer (n=3). At the start of immunotherapy, 21.9% of patients had locoregional relapse and 78.1% distant metastases. The proportion of patients with de novo metastatic CC was 12.5%. The vast majority had a satisfactory somatic condition at the start of therapy – ECOG 0-1 (80.2%). The response to therapy was assessed according to the iRECIST criteria. Statistical analysis was performed using StatTech v. 4.8.11. Patient survival function was estimated using the Kaplan–Meier method. Results. The objective response rate was 29.2% (n=28), disease control was achieved in 52.1% (n=50) of patients. The median time to response was 3.0 months (1.8–16.0 months), the median duration of response was 14.0 months (1.9–53.2 months). Median рrogression-free survival was 7.6 months (95% confidence interval – CI 5.0–11.0), the median overall survival was 24.0 months (95% CI 15.0–32.4). The median overall survival in the local recurrence group was 11.5 months (95% CI 3.4–22.2), in the group with metachronous metastases – 32.4 months (95% CI 21.4–72.2), and in the group with initially metastatic cancer – 7.8 months (95% CI 5.2–28.5). Conclusion. Monotherapy with pembrolizumab has shown high efficacy and manageable safety in patients with advanced CC. However, these advantages are primarily observed in the group of patients with metachronous distant metastases. The presence of an unresected or unirradiated primary or recurrent tumor contributes to poorer outcomes with immunotherapy.
Aim. To identify mutational profile differences of non-muscle-invasive (NMIUC) and muscle-invasive urothelial carcinoma (MIUC) of the bladder, assessed through isolating alterations in deoxyribonucleic (DNA) and ribonucleic (RNA) acids by a next-generation sequencing (NGS) method using a panel of 523 genes. Materials and methods. Tumor tissue and medical data of 72 patients with histologically confirmed bladder UC were studied. NMIUC was diagnosed in 40 (55.6%) patients, and MIUC in 32 (44.4%) patients. In 25 (34.7%) samples the tumor grade was assessed as low: 24 (33.3%) with NMIUC and 1 (1.4%) with MIUC, and in 47 (65.3%) as high: 16 (22.2%) with NMIUC, 31 (43.1%) with MIUC. In isolated tumor cells DNA and RNA alterations were detected by NGS using a panel of 523 genes. Results. NMIUC, compared to MIUC, was characterized by a lower median mutational burden (9.9 mut/Mb vs. 11.8 mut/Mb, respectively; p=0.037) and was associated with a higher rate of mutations of the FGFR/FGF (p=0.059) and STAG2/IRF (p=0.055) signaling pathways genes, as well as the FGFR3 (p=0.001) and STAG2 (p=0.026) genes with a lower rate of aberrations of the p53 signaling pathway genes (p=0.005), TP53 (p=0.001) and FGF4 (p=0.057). The low grade NMIUC samples had a lower rate of high mutational burden (vs. high grade NMIUC, p=0.004; vs high grade MIUC, p=0.067) and were also associated with a higher rate of FGF/FGFR signaling pathway gene mutations (vs. high grade MIUC, p0.0001; vs. high grade NMIUC, p0.0001), mainly due to FGFR3 alterations (vs. high grade NMIUC; p0.0001; vs. high grade MIUC; p0.0001). Low grade NMIUC, compared to high grade MIUC, had a higher rate of PIK3CA (p=0.027) and KDM6A (p=0.001) mutations. The mutational profile of high grade NMIUC and high grade MIUC did not differ significantly. High grade MIUC, compared to low grade NMIUC had a higher rate of mutations of the p53 pathway genes (p=0.008), including TP53 (p=0.001), and a significantly lower rate of alterations of the FGF/FGFR signal pathway genes (p0.0001), including FGFR3 (p0.0001), as well as the STAG2/IRF pathway genes (p=0.035) and the PIK3CA gene (p=0.027). Conclusion. Differences of the histological structure and natural history of low grade NMIUC, high grade NMIUC, and high grade MIUC are due to significant differences in their mutational status. NMIUC has a high rate of mutations in genes of the FGF/FGFR signaling pathway and inactivating mutations in STAG2 and KDM6A genes. MIUC typically has driver mutations that inactivate the p53 signal pathway. High grade NMIUC has alterations typical for both NMIUC (FGF/FGFR pathway gene mutations) and MIUC (p53 pathway gene mutations).
Background. Current information of the prognosis of mixed-type gastric cancer (GC) is poor. A few studies have shown that mixed GC differs from other types in the Lauren classification by more frequent of the lymph nodes metastasis and an aggressive behavior. Aim. To study the prognosis of mixed GC versus other Lauren GC types and evaluate the prognostic value of the predominant component in mixed carcinoma. Materials and methods. 315 patients with GC were reviewed by using a semi-quantitative assessment of the proportion of the diffuse and intestinal components of the tumor after surgical treatment by evaluation of the specimens slides to clarify the type of GC according to the Lauren classification, as well as the proportion of each component in the mixed GC. 166 patients (52.7%) with GC had the intestinal type, 72 (22.8%) had the diffuse type, 60 (19.0%) had the mixed type, and 17 (5.4%) had an unclassified type. Results. Mixed-type GC exhibited more aggressive behavior than intestinal and diffuse types of GC. It was characterized by deeper invasion of the gastric wall and more extensive lymphogenic metastasis. Early cancer (pT1b) was diagnosed in only 1 (1.7%) case, while in intestinal and diffuse types, it was detected in 18.6% and 29.2% of patients (p0.01), respectively. Invasion into the serous membrane of the stomach was reported in 56.7% of cases versus 45.1% (p=0.1270) and 27.7% (p=0.0008), respectively. Mixed GC metastasized to regional lymph nodes metastasis more frequently than intestinal or diffuse cancer (80% vs. 59.0% and 29.2%, respectively; p0.004). The average number of lymphogenic metastases was significantly higher than in intestinal and diffuse GC types (6.73±7.51 vs 3.58±5.04 and 2.15±4.39, respectively; p0.001). More frequently lymph node involvement in patients with mixed GC was observed with a similar depth of tumor invasion in the compared groups. In the study population, the 5-year overall survival (OS) in patients with mixed-type GC was significantly lower than in patients with intestinal and diffuse-type GC: 26.4% vs. 58.7% (p=0.00000) and 51.1% (p0.03). Stage-by-stage analysis showed significant differences in OS between mixed and intestinal GC in the largest group of patients with stage III disease and found no significant differences between mixed and diffuse GC at any stage. If the diffuse component was prevailed in patients with mixed-type GC, the 5-year OS rate was 37.9%; if the intestinal component prevailed, there were no survivors 5 years after surgery, and the 3-year OS rate was 12.8% (Log rank test; p=0.022). The frequency of metastatic lesions of regional lymph nodes in subgroup 1 was lower than in subgroup 2 (74.4% vs. 94.1%; p=0.0856). Conclusion. Mixed GC is diagnosed in later stages compared to other types of GC according to the Lauren classification, which translates into lower OS rates. This histological type shows a higher rate of lymphatic metastases, even with the same depth of tumor invasion. In a step-by-step analysis, OS in patients with mixed GC was significantly worse than that in the intestinal type, and was comparable to the results of treatment of diffuse GC. The predominant component assessment in mixed carcinoma may prove to be an additional prognostic factor.
Multiple myeloma (MM) is a clonal malignant lymphoproliferative disease with a continuously recurrent course. There has been a significant evolution of approaches to MM therapy, including the use of new induction regimens with not three, but four drugs with different mechanisms of action. This approach applies to patients both eligible and non-eligible for autologous hematopoietic stem cell transplantation (auto-HSCT). Thus, an international randomized clinical trial has shown the efficacy and safety of adding isatuximab (an anti-CD38 monoclonal antibody) to triplet therapy in patients with newly diagnosed MM. The publication presents two authors’ clinical cases of the use of the Isa-VRd induction regimen in patients with newly diagnosed MM. In a 61-year-old patient to undergo auto-HSCT (transplantation is not scheduled as initial therapy), after 4 induction cycles with Isa-VRd regimen, the combined positron-emission and X-ray computed tomography showed a pronounced decrease in the metabolic activity of tumor tissue, a negative status of minimal residual disease was achieved with the sensitivity of the NGF (next generation flow) method of 10⁻⁵; currently, maintenance therapy is ongoing. In a 63-year-old patient, a candidate for auto-HSCT, after completing 3 cycles of induction therapy with Isa-VRd quadruplet and an auto-HSCT, strict complete remission of the disease was achieved according to the International Myeloma Working Group (IMWG) 2016 criteria. Maintenance therapy is currently ongoing.
Overexpression and ligand-dependent internalization of prostate-specific membrane antigen (PSMA), followed by its accumulation in prostate cancer (PCa) cells, make this glycoprotein a good target for radionuclide-based targeted therapy. Currently, the only drug in this group with efficacy proven in a large randomized clinical study in patients with metastatic castration-resistant PCa is 177Lu-PSMA-617. The article presents an overview of the data on the mechanism of action and the results of completed studies of radioligand therapy (RLT) with 177Lu-PSMA for PCa, the current indications for this type of treatment in patients with a castration-resistant phase of the disease, and practical guidelines for RLT, including its planning, implementation, monitoring of effectiveness, and radiation protection measures. Clinical cases of patients with partial response/stabilization of the disease during RLT, significant improvement/complete response, and progression of PCa are presented.
