Journal of Modern Oncology

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. 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.

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. 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.

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.