Non-small cell lung cancer (NSCLC) patients with EGFR mutations usually receive continuous treatment with tyrosine kinase inhibitors (TKIs) until disease progression. We evaluated whether surgical excision of residual tumor masses offers a survival advantage when performed before progression on TKI therapy. We conducted a retrospective analysis of 230 patients with locally advanced or metastatic EGFR-mutated NSCLC who were treated with first-line EGFR TKI. Among these subjects, surgical intervention appeared technically feasible in 57 patients, 41 of whom underwent cytoreductive surgery while 16 were not operated for various reasons. Both surgically treated and nonsurgically treated patients received TKI until disease progression. The median duration of TKI treatment before surgery was 7.3 months. There was no perioperative mortality, while 8/41 (19.5%) patients experienced surgery-related complications. The median progression-free survival (PFS) and overall survival (OS) in the surgically treated group were 28.4 months and 46.9 months, respectively. These outcomes were significantly better than in patients with potentially resectable disease who did not undergo surgery (PFS: 15.4 months, p = 0.010; OS: 26.5 months, p = 0.015), or in subjects not amenable to cytoreduction (PFS: 19.0 months, p = 0.006; OS: 31.7 months, p = 0.001). Mutation analysis of residual tumor tissues revealed emerging TKI-resistant clones in 4 of 21 investigated patients. At the time of data cut-off, 12/41 (29%) surgically treated patients remained disease-free. In conclusion, surgical removal of residual tumor masses in EGFR-mutated NSCLC during response to TKI may confer a survival advantage.

106 Background: Neoadjuvant immunotherapy (IO) with anti–PD-1 inhibitors has shown promise in microsatellite instability–high (MSI-H) locally advanced gastric cancer (LAGC), with potential to improve treatment radicality. We evaluated 3-year overall survival in patients with MSI-H LAGC treated with neoadjuvant anti–PD-1 monotherapy without planned surgery. Methods: Among 405 patients with LAGC screened between 2019 and 2025, 27 (6.7%) had MSI-H tumors and received neoadjuvant anti–PD-1 IO. Of these, 9 (33.3%) were not operated and were included in this analysis. Treatment consisted of nivolumab 240 mg IV q2w (n = 4) or pembrolizumab 200 mg IV q3w (n = 5). The median number of cycles was 13 (range, 2–50). Reasons for omitting surgery were patient refusal (n = 7), medical contraindications (n = 1), or disease progression on therapy (n = 1). Tumor response was assessed radiologically and endoscopically with biopsy. Survival was estimated using Kaplan–Meier methodology. Results: Median age was 78 years (range, 56–86); 6 patients were >75 years, and 7/9 were female. Stage was IIB in 4 and IIIB in 5 patients. The objective response rate (ORR) was 7/9, including 6 complete responses (CR) and 1 partial response (PR). Median time to best response was 68 days (range, 33–512). One patient had stable disease (SD), and 1 had progressive disease (PD) after 2 cycles of IO. At data cut-off, 5/9 patients had discontinued IO due to confirmed CR by PET–CT and endoscopic biopsy (n = 2), refusal to continue therapy (n = 1), tumor progression–related death (n = 1), or comorbid pathology (diabetes mellitus with ketoacidosis; n = 1). The median number of treatment cycles was 30 (range, 2–50). Four patients remained on therapy (median, 13 cycles; range, 12–46). Median progression-free survival and overall survival were not reached. Estimated 3-year overall survival was 77.8%. Two patients have been followed for 71.5 and 60 months, respectively, without evidence of disease progression. No grade ≥3 immune-related adverse events or clinically significant treatment-related toxicities were observed. Conclusions: In this highly selected cohort of patients with MSI-H LAGC, non-operative management after neoadjuvant anti–PD-1 IO was associated with high CR rates and durable survival. A 3-year OS of 77.8% suggests that omission of surgery may be feasible for selected MSI-H responders.

ER-low, metastatic breast cancer, endocrine therapy, iCDK4/6, chemotherapy

The efficacy of immune checkpoint inhibitors (ICIs) in non-small-cell lung cancer (NSCLC) varies widely across patients. Growing evidence indicates that the gut microbiome, through its interaction with the tumor microenvironment, may influence the response to immunotherapy. To investigate this, we analyzed fecal and tumor samples from 63 patients with inoperable NSCLC undergoing ICI therapy. Based on microbiome profiling using 16S rRNA sequencing, patients were grouped according to treatment benefit, defined as progression-free survival (PFS) of six months or longer. Associations between α-diversity indices, microbial composition at the genus and phylum levels, and a composite Sum Index of Binary Abundance (SIBA) were examined in relation to clinical outcomes. Higher microbial α-diversity was linked to improved response to ICIs (p-value = 0.0078 for the Chao1 index). Multiple specific taxa, such as Ruminococcus gauvreauii (p-value = 2 × 10−4), Ruminiclostridium 9 (p-value = 8 × 10−4), and [Eubacterium] ventriosum (p-value = 9 × 10−4), were enriched in patients with favorable outcomes, whereas Oscillibacter and the Eubacterium hallii group were associated with disease progression (p-value = 2 × 10−3 and 9 × 10−3, respectively). The SIBA index, which reflects the absence of multiple beneficial bacterial taxa, proved to be a stronger predictor of treatment response than individual taxa alone. Median SIBA values were 18 vs. 24 in patients benefiting from IO therapy compared to non-responders (p-value = 9 × 10−7). These findings suggest that gut microbiome diversity and composition are closely tied to immunotherapy outcomes in NSCLC. Composite microbial metrics like SIBA may enhance predictive accuracy and inform personalized treatment approaches.

gastric cancer,neoadjuvant therapy,immunotherapy,targeted therapy

Background/Objectives: Checkpoint inhibitors (ICIs) are key therapies for NSCLC, but current selection criteria, such as excluding mutation carriers and assessing PD-L1, lack sensitivity. As a result, many patients receive costly treatments with limited benefit. Therefore, this study aimed to predict which NSCLC patients would achieve durable survival (≥24 months) with immunotherapy. Methods: A comprehensive ensemble radiomics approach was applied to pretreatment CT scans to prognosticate overall survival (OS) and predict progression-free survival (PFS) in a cohort of 220 consecutive patients with inoperable NSCLC treated with first-line ICIs (pembrolizumab or atezolizumab, nivolumab or prolgolimab) as monotherapy or in combination. The radiomics pipeline evaluated four normalization methods (none, min-max, Z-score, mean), four feature selection techniques (ANOVA, RFE, Kruskal-Wallis, Relief), and ten classifiers (e.g., SVM, random forest). Using two to eight radiomics features, 1680 models were built in the Feature Explorer (FAE) Python package. Results: Three feature sets were evaluated: clinicopathological (CP) only, radiomics only, and a combined set, using 6- and 12-month PFS and 24-month OS endpoints. The top 15 models were ensembled by averaging their probability scores. The best performance was achieved at 24-month OS with the combined CP and radiomics ensemble (AUC = 0.863, accuracy = 85%), followed by radiomics-only (AUC = 0.796, accuracy = 82%) and CP-only (AUC = 0.671, accuracy = 76%). Predictive performance was lower for 6-month (AUC = 0.719) and 12-month PFS (AUC = 0.739) endpoints. Conclusions: Our radiomics pipeline improved selection of NSCLC patients for immunotherapy and could spare non-responders unnecessary toxicity while enhancing cost-effectiveness.

В данном разделе указаны критерии оценки клинической значимости применения дорогостоящей противоопухолевой лекарственной терапии в соответствии со шкалой, разработанной экспертной группой (см. стр. 7). В тексте они обозначены, как магнитуда клинической значимости (МКЗ).

Введение. На фоне возрастающего объема используемой специфической лекарственной терапии по всей стране создаются рекомендации и инструкции по использованию противоопухолевых препаратов, а также внедряются кабинеты и отделения централизованного разведения, однако результаты такой работы отражены в единичных публикациях за короткий промежуток времени. Цель. Проанализировать целесообразность создания и эффективность работы отделения централизованного разведения в городском онкологическом медицинском учреждении на примере Санкт-Петербургского клинического научно-практического центра специализированных видов медицинской помощи (онкологический) им Н.П. Напалкова. Материалы и методы. Анализ проведен с использованием имеющихся электронных и бумажных носителей (журналов) отделения, заявок на выполнение разведения и данных аптеки по закупке лекарственных препаратов за период 2014-2024 гг. Результаты. Создание отделения позволило повысить безопасность персонала и пациентов при проведении химиотерапии, уменьшить количество ошибок при выполнении назначений, повысить контроль за назначением лекарственных средств и их списанием, уменьшить нагрузку на медицинских сестер клинических отделений и повысить качество приготавливаемых растворов. Работа отделения позволяет экономить 10 % от закупки лекарственных препаратов, относительно децентрализованного разведения. Остается потребность в нормативной базе, рекомендациях по работе кабинетов/отделений централизованного разведения, а также контроле качества приготовленных растворов. Выводы. Работа отделения централизованного разведения лекарственных препаратов в ГБУЗ «СПб КНПЦСВМП(о) им Н.П. Напалкова» пример эффективного использования противоопухолевых препаратов, особенно в условиях возрастающей стоимости лечения пациентов и дефицита бюджета здравоохранения. Практика онкологического центра им. Н.П. Напалкова может использоваться в других медицинских организациях для более рационального применения химиотерапевтических препаратов.

e20571 Background: Checkpoint inhibitors (ICI) are an important part of the NSCLC treatment algorithm. Existing criteria for ICI efficacy prognostication rely on exclusion of activating mutations carriers and PD-L1 expression. Still the sensitivity of this approach is not sufficient and significant percentage of patients receive ineffective expensive treatment with an elevated risk of side effects. We aimed to define whether additional information drawn from the baseline CT scans and interpreted with a machine learning model might help to improve the accuracy of selection for IO clinical benefit. Methods: We included patients with inoperable NSCLC treated in 1 st or 2 nd line with ICI (pembrolizumab and bioanalogues, atezolizumab, nivolumab or prolgolimab) either as monotherapy or a combination. Clinical benefit was defined as overall survival equal or above 24 months. Tumor volume was marked by a certified radiologist using 3D Slicer. Our radiomics pipeline integrated four types of normalization (none, MinMax, Z-score, Mean), preprocessing methods (ANOVA, RFE, KW, Relief), ten classifiers (SVM, LDA, Logistic Regression, AdaBoost, Gaussian Process, AE, Random Forest, LR-Lasso, Decision Tree, Naïve Bayes), and instruction to classifiers to select 2–20 radiomics features. This resulted in construction of 6,080 models using Feature Explorer (FAE) programmed with Python and utilizing NumPy, pandas and scikit-learn modules. Results: We included CT scans from 239 sequential patients with inoperable NSCLC. The best prognostically performing model was selected based on the AUC, accuracy, MCC, PPV and NPV in the validation datasets and independent internal test set. An optimal model was achieved by combining z-score normalization, the removal of outcome-unassociated features by ANOVA, and LASSO feature selection. It included only two out of 2141 calculated radiomics features: wavelet-LLL-NGTDM-strength and Logarithm-GLSZM-SizeZoneNonUniformityNormalized. Such small model improved the model’s ability to generalize to unseen data, achieving an AUC of0.792, accuracy of 84.7%, MCC of 0.533, PPV of 0.471 and NPV of 0.962 in the independent internal test set. The best-performing model (age, platelet count) including only clinicopathological features achieved a predictive AUC of 0.680 and an accuracy of 72.3%, while the best model combining both clinicopathological and radiomics features reached the AUC of 0.816 with an accuracy of 81.2%. Conclusions: Overall, our study highlights that radiomics can achieve very good performance in the prognostication of clinical benefit, defined as prolonged overall survival in patients with lung cancer treated with ICI. Prognostic models developed in this study may potentially provide a clinical predictor of disease outcome outperforming routinely used clinicopathological parameters.

Purpose This research work evaluates monotherapy with checkpoint inhibitors (CPI). as a neoadjuvant treatment for patients with Microsatellite Instability-High (MSI-H) locally advanced gastric cancer. Methods Here we present the results of the retrospective study from Napalkov Cancer Center over 4.5 years on patients with MSI-H locally advanced gastric cancer. A total of 566 patients were analyzed, 18 of whom were included in the research, focusing on clinical response rate, surgical pathology, 'watch and wait' strategy, and safety outcomes on an exploratory basis. Patients were assigned to four to eight neoadjuvant cycles of CPI, followed by surgery. Results The objective response to neoadjuvant CPI in patients with MSI-H gastric cancer was 77.8%. Complete response was achieved in five (27.8%) and partial response in nine (50%) patients, accordingly. Surgery was performed on 14 patients. Complete margin-free (R0) resection rates were 100%. Downstaging was observed in 12 out of 14 patients. Histopathologic complete response rates (pathologic complete response or Tumor Regression Grade-major response (TRG1)) were achieved in eight (57.1%) patients. No disease progression was detected with a median follow-up of 33.7 months (4.4-55.7 months). Clinically significant adverse events were not observed. Conclusion CPI in a neoadjuvant setting for patients with MSI-H locally advanced gastric cancer is highly effective and safe.

e20553 Background: PD-(L)1 inhibitors are approved immunotherapy agents in treatment for mNSCLC, however, limited data exists about switching between different anti-PD1 antibodies. Our study aimed to evaluate the safety and efficacy of the interchangeability of nivolumab, pembrolizumab, and atezolizumab in patients (pts) with mNSCLC in the 2nd and 3rd line. Methods: We retrospectively evaluated data of pts with mNSCLC treated in four oncology centers in Moscow and SaintPetersburg (Russia). Inclusion criteria were as follows: histologically confirmed mNSCLC with no driver mutations, performance status ECOG 0-2, monotherapy of anti-PD(L)1 antibody, and switching to another PD(L)1 inhibitor for any reason except progression disease or toxicity after initiating of immunotherapy. The primary end-point was progression-free survival (PFS), and secondary end-points were the rate of all grades and grade 3-4 adverse events (CTC AE 5.0). A sample size of 83 achieves 80% power to detect an equivalence difference of 15% in 3-months PFS after the change of anti-PD1 antibody with a one-sided significance level of 0,05. Results: A total of 103 patients (27% female) were included with a mean age of 66 years (33-93). 0-1, 2, and ≥3 organs with metastases have 70 (68%), 17 (17%), and 16 (16%) pts, respectively. Performance status ECOG 0, 1, and 2 was in 16 (16%), 70 (68%), and 17 (17%) pts, respectively. 50 (48%) patients received pembrolizumab, 40 (39%) pts received nivolumab, and 13 (13%) pts – atezolizumab. 48 (47%) pts were switched to atezolizumab, 28 (27%) pts were switched to nivolumab, 26 (25%) pts – to pembrolizumab. The median duration of treatment with the first anti-PD(L)1 antibody was 6 months (1-53 months), with the second PD(L)1-inhibitor was 3 months (1-41 months). Within 3 months after 1 replacement of the drug, there were 77 (74,7%) pts without progression. With the median follow-up of 8 months (1-41), the estimated 3-month PFS was 79,3%. The efficacy of switching was not associated with the agent (HR 0,97, 95CI 0,68-1,38, p = 0,9). There were 2 cases of AEs of 3-4 grades when switching to the second drug. Conclusions: Switching from one anti-PD(L)1 antibody to another in pts with mNSCLC is possible in case of limited access to PD(L)1 inhibitors.

Background. The use of cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors in combination with endocrine therapy is a key initial treatment for advanced luminal HER2-negative (HR+/HER2-) breast cancer. The approval studies MONALEESA-2 and 7 demonstrated the efficacy and safety of ribociclib in combination with aromatase inhibitors as a first-line treatment in post- and premenopausal patients. In the Phase lllb CompLEEment-1 study, the same treatment regimen was evaluated in an extended patient population in terms of both safety and efficacy. The article presents an analysis of data from a subgroup of patients from Russia. Materials and methods. The study included 129 patients from Russia who met the inclusion criteria for the CompLEEment-1 study. The primary endpoint was the incidence of adverse events (AEs) at a median follow-up of 25.4 months. Secondary endpoints were median progression-free survival, objective response rate, and disease control. Results. The efficacy and safety results of the therapy in the subgroup of patients from Russia were consistent with the general population of patients included in CompLEEment-1. The incidence of AEs requiring dose adjustment or treatment interruption was 58.1%, and the permanent discontinuation rate was 15.5%. The most frequently reported treatment-related AEs grade 3 or higher were neutropenia and transaminase increased. Conclusion Data obtained in a subgroup of patients from the Russian Federation confirm the safety and tolerability of ribociclib in an extended population of patients with HR+/HER2- breast cancer in settings close to the real world.