Second Chance for Cure: Stereotactic Ablative Radiotherapy in Oligometastatic Disease.

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.

Obtaining Gene-Modified HLA-E-Expressing Feeder Cells for Stimulation of Natural Killer Cells.

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 CD56brightHLA-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.

Cardiac dose in the treatment of synchronous bilateral breast cancer patients between three different radiotherapy techniques (VMAT, IMRT, and 3D CRT).

PURPOSE: Synchronous bilateral irradiation of both mammary glands and chest wall is a challenging task due to technical difficulties and limited evidence supporting an optimal technique to improve treatment outcomes. We studied and compared the dosimetry data of three radiotherapy techniques to select the most optimal one. METHODS: We compared three-dimensional conformal radiation treatment (3D CRT), intensity-modulated radiation therapy (IMRT), and volumetric modulated arc therapy (VMAT) during irradiation of synchronous bilateral breast cancer in nine patients followed by examination of dose distribution to the cardiac conduction system (SA node, AV node and Bundle of His), myocardium, lungs, left anterior descending artery (LADA) and right coronary artery (RCA) . RESULTS: VMAT is the most sparing technique for SBBC treatment. Even though doses to the SA node, AV node and Bundle of His were higher with VMAT (Dmean were 3.75 ± 0.62, 2.58 ± 0.83 and 3.03 ± 1.18 Gy respectively) compared with 3D CRT (Dmean were 2.61 ± 0.66, 1.52 ± 0.38 and 1.88 ± 0.70 Gy respectively), this difference is statistically insignificant. Doses to the right and left lung (average Dmean = 12.65 ± 3.20 Gy, V20Gy = 24.12 ± 6.25%), myocardium (Dmean = 5.33 ± 1.51 Gy, V10Gy = 9.80 ± 3.83%, V20Gy = 7.19 ± 3.15%, V25Gy = 6.20 ± 2.93%), and LADA (Dmean = 10.04 ± 4.92 Gy, V20Gy = 18.17 ± 13.24% and V25Gy = 15.41 ± 12.19%) were highest with 3D CRT. The highest  Dmean in the cardiac conduction system (5.30 ± 2.23, 3.15 ± 1.61 and 3.89 ± 1.85 Gy respectively) was observed with IMRT, and a similar effect was noted in RCA (Dmean = 7.48 ± 2.11 Gy). CONCLUSION: VMAT is the optimal and satisfactory radiation therapy technique for sparing organs at risk (OARs). With VMAT, a lower Dmean value was noted in the myocardium, LADA, and lungs. The use of 3D CRT significantly increases the dose of radiation reaching the lungs, myocardium, and LADA, which can subsequently cause cardiovascular and lung complications, but not in the cardiac conduction system.