Matea Lekić

Ultrahypofractionated whole-breast radiotherapy reduces treatment burden but increases the importance of accurate dose delivery at each fraction. This retrospective single-center study evaluated cone-beam computed tomography-guided online adaptive radiotherapy in 55 patients with early-stage breast cancer treated with 26 or 27 Gy in five fractions. Dosimetric analysis was available for 52 patients and 259 paired scheduled and adapted fractions. Linear mixed-effects models with a patient-specific random intercept were used to account for repeated fractions within individual patients. The adapted plan was selected for 242 out of 260 delivered fractions (93.1%). Mean planning target volume V95% increased from 93.52 ± 2.94% with the scheduled plan to 98.13 ± 1.04% with adaptation (p < 0.001), with reduced interfraction variability. Ipsilateral lung V30% increased modestly from 13.94% to 14.96% (p < 0.001). In left-sided cases, no significant differences were observed for heart V25% (1.400% vs. 1.395%; p = 0.3825) or left anterior descending coronary artery D0.03 cm³ (1.771 vs. 1.873 Gy; p = 0.1390). Acute grade 1 toxicity occurred in five patients (9.1%), with no grade ≥ 2 events. Mean treatment-session duration was 28 min. Online adaptation significantly improved daily target coverage and was technically feasible within a five-fraction whole-breast workflow. Acute toxicity was limited in this cohort, while longer follow-up and cumulative dose analyses are needed to further define its impact on organ-at-risk exposure and clinical outcomes.

Background/Objectives: Metastatic melanoma increasingly includes clinical scenarios in which metastasis-directed treatment may complement systemic immunotherapy, particularly in oligometastatic disease. We evaluated outcomes of stereotactic body radiotherapy (SBRT) combined with immunotherapy in patients with metastatic melanoma, focusing on local control, survival, treatment sequencing, and safety. Methods: In this retrospective single-center study, 63 patients underwent SBRT for 97 extracranial metastatic lesions while receiving immune checkpoint inhibitors. The primary endpoint was local control (LC), while secondary endpoints included progression-free survival (PFS), overall survival (OS), and treatment-related toxicity. Results: LC rates at 12, 24, and 36 months were 95.9%, 89.7%, and 89.7%, respectively, demonstrating durable long-term control of treated lesions. Median OS was 47 months, while median PFS was not reached. A numerical trend toward longer PFS was observed among patients receiving SBRT during immunotherapy, although the differences were not statistically significant. No significant differences in LC were identified across oligometastatic disease subcategories. Combined treatment was well tolerated, with predominantly low-grade toxicity and no signal of increased immune-related adverse events. Conclusions: SBRT combined with immunotherapy appears to be a feasible and effective metastasis-directed treatment strategy in selected patients with metastatic melanoma. Durable local control, encouraging survival outcomes, and favorable tolerability support further prospective studies to optimize treatment sequencing and the integration of local and systemic therapies.

Online adaptive radiotherapy mitigates errors in absorbed dose delivery due to daily anatomical changes during hypofractionated breast treatment, particularly when comprehensive nodal therapy includes the internal mammary chain. To illustrate this, we present a case of a 65-year-old woman with left-sided luminal B invasive carcinoma, who underwent segmentectomy and level 1–2 dissection. Pathology revealed an 18 × 15 × 13 mm primary tumor with lymphovascular invasion, two of eleven axillary nodes positive, and intramammary metastasis, staged pT1cN1a. She received adjuvant docetaxel–cyclophosphamide followed by letrozole. Hypofractionated radiotherapy (40 Gy in 15 fractions) was administered in an inspiration breath-hold setting using a CBCT-guided online-adaptive platform. Adaptive planning improved V95% coverage over the planned treatment for all targets: on average, whole breast coverage increased from 88.4% to 96.3%, supraclavicular from 93.0% to 97.1%, axilla from 90.6% to 96.7%, and internal mammary from 91.8% to 95.9%. Organ-at-risk metrics remained within limits: the mean heart dose increased slightly (from an average of 0.12 Gy in scheduled to 0.15 Gy in adaptive plans). At the same time, the LAD D0.03 cm³ decreased, and the heart V4 Gy fell modestly (from 13.3% in the scheduled plan to 8.2% in the adaptive plan), reflecting low-dose redistribution without exceeding constraints. Lung and thyroid mean doses remained comparable. The patient tolerated treatment well, with no acute toxicity or local recurrence. This case highlights the importance of daily adaptation for complex left-sided radiation treatment involving internal mammary nodes, demonstrating target recovery without exceeding absorbed dose constraints and supporting future studies on control, toxicity, and quality of life.

Background: The aim of this retrospective, single-arm study was to present the technique and preliminary efficacy and safety results of a single-fraction SBRT for LAPC using total intravenous anaesthesia and optical surface guidance as motion management. Methods: Fifty-five patients with locally advanced pancreatic cancer were treated with SBRT with a single-fraction receiving a median BED₁₀ = 128.9 Gy. Forty-two patients received systemic treatment. End points were OS, FFLP, PFS, and toxicity. Actuarial survival analysis and univariate analysis were investigated. Results: The median follow-up was 15 months, mean OS was 18 months (95% CI: 16.7 to 19.3), and the one-year FFLP and 1-year OS were 100% and 90.9% (95% CI: ± 1.5%), respectively. Median PFS was 12 months (95% CI: 9.5 to 14.4), and 1-year PFS was 85.5% (95% CI: ± 1.4%). Thirty-five patients (63.6%) were alive at the time of analysis. No acute/late toxicity > G2/G1 was reported. Conclusions: SBRT for LAPC using total intravenous anaesthesia and optical surface guidance presented as an effective and safe treatment with very low toxicity.

Background: The aim of this study was to present the technique and preliminary results of efficacy and safety for single-fraction SBRT for LAPC using Total Intravenous Anaesthesia and Optical Surface Guidance as motion management. Methods: Fifty-five patients were treated with SBRT in a single-fraction receiving median BED₁₀ = 128.9 Gy. Forty-two patients received systemic treatment. End points were OS, FFLP, PFS, and toxicity. Actuarial survival analysis and univariate analysis were investigated. Results: Median follow-up was 15 months. Mean OS was 26.7 months. One-year FFLP and 1-year OS were 100% and 90.9%, respectively. Median PFS was 18 months, and 1-year PFS was 85.5%. Thirty-five patients (63.6%) were alive at the time of analysis. No acute/late toxicity > G2/G1 was reported. Conclusions: SBRT for LAPC using Total Intravenous Anaesthesia and Optical Surface Guidance presented as an effective and safe treatment with very low toxicity.

Melanoma progression is influenced by complex interactions between tumor cells and the immune microenvironment. This study examined the relationship between microphthalmia-associated transcription factor (MITF) expression and the immune microenvironment in primary melanoma using a modified classification of tumor-infiltrating lymphocytes (TILs) based on conventional BRISK categories. Archival formalin-fixed, paraffin-embedded tissue samples from 81 primary melanoma patients were analyzed via tissue microarray immunohistochemistry to assess MITF protein levels. TIL patterns were categorized into six groups, refining the traditional BRISK classification to distinguish between continuous and discontinuous infiltration, as well as peripheral vs intratumoral distribution. The analysis revealed that melanomas classified under the BRISK B category exhibited the highest MITF expression, often exceeding 50%. In contrast, tumors in the NON-BRISK and ABSENT TIL groups showed significantly lower MITF expression (mean values: 32.73% ± 16.98% and 22.00% ± 10.54%, respectively), with statistically significant differences (Kruskal–Wallis test, P = 0.027; modified classification, P = 0.011). Additionally, the presence of CD20+ B lymphocytes correlated with increased MITF expression (P = 0.009). MITF gene amplification was detected in 29% of cases, though its association with protein expression showed only a trend (P = 0.058). These findings highlight the complex interplay between MITF expression and TIL distribution in melanoma, suggesting that refined TIL classification may offer deeper insights into tumor immunobiology and help predict responses to immunotherapy.

Purpose: To assess the efficacy and safety of stereotactic body radiotherapy for patients with unresectable, locally advanced pancreatic cancer using Optical Surface Management System – AlignRT (OSMS-AlignRT) as an optical body surface motion management in deep breath hold. Patients and Methods: Forty-five patients diagnosed with locally advanced pancreatic cancer were treated with stereotactic body radiotherapy in 3 or 5 fractions, and received varying BED₁₀ (median 79.5 Gy) from April 2017 to December 2020. All patients were treated in deep breath hold with OSMS-AlignRT used as optical body surface motion management. Thirty-three patients received systemic treatment before and/or after stereotactic body radiotherapy, and twelve patients received no systemic treatment. In this retrospective, observational, single-arm study, primary endpoints were overall survival and freedom from local progression (ie, local control). Secondary endpoints were progression-free survival and toxicity. Actuarial survival analysis and univariate analysis were investigated. Results: Data from forty-five patients were analyzed. Median follow-up was 15 months. One-year freedom from local progression and survival were 95.5% and 71.1%, respectively. Median progression-free survival was 14 months. Median overall survival from diagnosis for all patients was 17 months, and 19 months for patients alive at the time of analysis. No patient had >G2 toxicity. Conclusion: Stereotactic body radiotherapy for locally advanced pancreatic cancer using OSMS-AlignRT as optical body surface motion management in deep breath hold patients is an effective and safe local treatment option, with no >G2 toxicity, and could be a promising therapeutic option with acceptable toxicity, either as a single treatment or in a multimodal regimen. OSMS-AlignRT provided accurate and reliable body surface motion management during stereotactic body radiotherapy.

(1) Background: the aims of this study were to determine the total extent of pancreatic cancer’s internal motions, using Calypso^® extracranial tracking, and to indicate possible clinical advantages of continuous intrafractional fiducial-based tumor motion tracking during SABR. (2) Methods: thirty-four patients were treated with SABR for LAPC using Calypso^® for motion management. Planning MSCTs in FB and DBH, and 4D-CTs were performed. Using data from Calypso^® and 4D-CTs, the movements of the lesions in the CC, AP and LR directions, as well as the volumes of the 4D-CT-based ITV and the volumes of the Calypso^®-based ITV were compared. (3) Results: significantly larger medians of tumor excursions were found with Calypso^® than with 4D-CT: CC: 29 mm (p < 0.001); AP: 14 mm (p < 0.001) and LR: 11 mm (p < 0.039). The median volume of the Calypso^®-based ITV was significantly larger than that of the 4D-CT based ITV (p < 0.001). (4) Conclusion: beside known respiratory-induced internal motions, pancreatic cancer seems to have significant additional motions which should be considered during respiratory motion management. Only direct and continuous intrafractional fiducial-based motion tracking seems to provide complete coverage of the target lesion with the prescribed isodose, which could allow for safe tumor dose escalation.