Alexey I. Popodko

Background. Oligometastatic disease (OMD) represents an intermediate state between localized and disseminated cancer, characterized by a limited number of metastases (typically 1–5). Stereotactic ablative radiotherapy (SABR) is a precise local treatment modality capable of delivering ablative doses to metastatic lesions of various sites with minimal toxicity. Despite growing clinical evidence, the impact of primary tumor type and metastatic site on survival outcomes after SABR remains insufficiently explored. Aim — to evaluate overall survival (OS) and progression-free survival (PFS) in patients with oligometastatic disease treated with SABR, and to analyze the association of these outcomes with the localization of the primary tumor and distant metastases. Methods. This retrospective cohort study included 68 patients with 1–5 metastatic lesions treated with SABR at the European Medical Center (Moscow) between 2015 and 2024. Total radiation doses ranged from 16 to 60 Gy in 1–7 fractions, depending on tumor histology and anatomic site. The median follow-up was 51 months (range: 11–75). Forty-nine patients (72%) received systemic therapy — chemotherapy, immunotherapy, or targeted therapy — selected individually according to treatment guidelines for each tumor type and clinical status. Treatment toxicity was evaluated according to CTCAE v4.0. Results. The 1-, 3-, and 5-year OS rates were 97.1%, 83.6%, and 73.4%, respectively; corresponding PFS rates were 57.3%, 36.6%, and 28.0%. Patients with bone metastases demonstrated a tendency toward improved OS (p = 0.049), whereas the localization of the primary tumor had no significant impact on survival (p = 0.41). Grade ≥ 2 toxicity occurred in 5.8% of patients. Conclusions. SABR was associated with favorable survival outcomes and acceptable tolerance in patients with oligometastatic disease. The site of metastases may represent a prognostic factor influencing long-term outcomes. Further prospective studies are warranted to validate these findings and to refine patient selection criteria for SABR as part of combined-modality treatment.

PURPOSE: Local ablative therapy, such as radiotherapy or surgery, plays a key role in treatment of patients with oligometastatic disease. Stereotactic ablative body radiotherapy (SABR) comes to the fore as a safe and effective treatment for patients with a limited number of metastases, even those located in hard-to-reach body sites. Many researchers have suggested that metastatsis-directed therapy could improve long-term progression-free survival (PFS) and overall survival (OS) in patients with oligometastases. PATIENTS AND METHODS: This was a retrospective, single-arm, observational study conducted between July 2015 and February 2022. In our institute, 60 patients with controlled primary tumors and one to five metastases were treated with SABR. Prescribed radiation doses ranged from 12 to 60 Gy administered in one to seven fractions. We aimed to determine whether metastatic-directed therapy using SABR for all oligometastases affects OS and PFS and whether the primary tumor or metastatic site influences OS/PFS. RESULTS: The most common primary malignancy types were prostate (n = 14), colorectal (n = 10), lung (n = 7), and breast cancers (n = 6). The median follow-up was 30 months, ranging from 9 to 79. The 1-, 3-, and 5-year PFS and OS rates were 54.9%, 37.0%, and 37.0% and 98.3%, 84.4%, and 73.8%, respectively, and the median time to first progression was 15 (range, 2-32) months. Twenty-four (40%) patients had no recurrence. In our analysis, primary tumor site was not an independent prognostic factor. The metastatic site may influence on patient outcome in cases of localized bone and liver metastases. CONCLUSION: In our retrospective analysis, SABR was associated with favorable levels of PFS and OS in patients with oligometastases. The limitations of our study were lacking high-level evidence, and randomized studies to compare SABR and palliative standard of care are mandatory.

Human cytomegalovirus (HCMV)-specific adaptive NK cells are capable of recognizing viral peptides presented by HLA-E on infected cells via the NKG2C receptor. Using retroviral transduction, we have generated a K562-cell-based line expressing HLA-E in the presence of the HLA-E-stabilizing peptide, which has previously shown the capacity to enhance adaptive NK cell response. The obtained K562-21E cell line was employed to investigate proliferative responses of the CD57⁻ NK cell subset of HCMV-seropositive and seronegative donors. Stimulation of CD57⁻ NK cells with K562-21E/peptide resulted in an increased cell expansion during the 12-day culturing period, regardless of the serological HCMV status of the donor. The enhanced proliferation in response to the peptide was associated with a greater proportion of CD56^brightHLA-DR⁺ NK cells. In later stages of cultivation, the greatest proliferative response to K562-21E/peptide was shown for a highly HCMV-seropositive donor. These expanded NK cells were characterized by the accumulation of CD57⁻KIR2DL2/3⁺NKG2C⁺NKG2A⁻ cells, which are hypothesized to represent adaptive NK cell progenitors. The K562-21E feeder cells can be applied both for the accumulation of NK cells as therapeutic effectors, and for the study of NK cell maturation into the adaptive state after the HLA-E peptide presentation.