Highly precise dose delivery to the target (tumor or cancerous tissue) is a key point when brain diseases are treated applying recent stereotactic techniques: intensity-modulated, image-guided radiotherapy, volumetric modulated arc therapy, Gamma knife radiosurgery. The doses in one single shot may vary between tens and hundreds of Gy and cause significant cell/tissue/organ damages. This indicates the need for implementation of quality assurance (QA) measures which are realized performing treatment dose verification with more than one calibrated quality assurance method or tool, especially when functional radiosurgery with a high dose (up to 40 Gy in our case) shall be delivered to the target using small 4 mm collimator. Application of two dosimetry methods: radiochromic film dosimetry using RTQA2 and EBT3 films and dose gel dosimetry using modified nPAG polymer gels for quality assurance purposes in stereotactic radiosurgery treatments using Leksell Gamma Knife© Icon™ facility is discussed in this paper. It is shown that due to their polymerization ability upon irradiation nPAG gels might be potentially used as a quality assurance tool in Gamma knife radiosurgery: they indicate well pronounced linear dose response in hypo-fractionated (up to 10 Gy) dose range and are sensitive enough to irradiation dose changes with a high (at least 0.2 mm) spatial resolution. Dose assessment sensitivity of gels depends on parameters of a dose evaluation method (optical or magnetic resonance imaging), however, is similar to this estimated using film dosimetry, which is set as a standard dosimetry method for dose verification in radiotherapy.

Background: Locally advanced rectal cancer (LARC) treatment selection between neoadjuvant intensified chemotherapy (NIC) and standard chemoradiotherapy (CRT) lacks validated predictive biomarkers. Interleukin-1β (IL1B) polymorphisms modulate IL-1β expression and may influence treatment-specific outcomes through tumor microenvironment remodeling. Methods: In this prospective, single-center, randomized, open-label noninferiority trial (NCT05378919), 150 patients with stage II–III rectal cancer were randomized 1:1 to NIC (FOLFOX4, 8 cycles; n=68) or CRT (50 Gy/25 fractions with concurrent fluoropyrimidine; n=82). The primary endpoint was 5-year disease-free survival (DFS; noninferiority margin HR ≤1.29, NIC vs. CRT). IL1B rs1143634 and rs16944 were genotyped by TaqMan assay. Treatment–genotype interactions were assessed using Cox regression with multiplicative interaction terms. Results: Noninferiority was not demonstrated: 5-year DFS was 54.4% (NIC) versus 68.1% (CRT) in the ITT population (HR 1.52, 95% CI 0.90–2.56; p=0.114), with the upper CI bound exceeding the prespecified margin of 1.29. Per-protocol DFS was significantly inferior for NIC (62.5% vs. 82.1%; HR 2.27, 95% CI 1.06–4.76; p=0.029). Overall survival and cancer-specific survival (CSS) did not differ significantly between arms. A statistically significant treatment–genotype interaction was identified for rs1143634 in CSS (interaction p<0.001): T-allele carriage (CT+TT) was associated with inferior CSS exclusively in the NIC arm (HR 4.84, 95% CI 1.04–22.43; p=0.044), with no prognostic effect in the CRT arm (HR 0.69; p=0.494). A DFS interaction was also significant (p=0.047). rs16944 showed a borderline CSS interaction (p=0.082). Conclusions: NIC (FOLFOX4) did not achieve DFS noninferiority versus CRT in unselected LARC patients. IL1B rs1143634 demonstrates a treatment-arm-specific prognostic effect on cancer-specific survival, with a highly significant treatment–genotype interaction (p<0.001) identified within a prospective randomized design with prespecified translational hypotheses, satisfying the formal criterion for predictive biomarker classification. Prospective validation in an adequately powered, biomarker-stratified trial is warranted.