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Simple Summary: This study assessed hypo-fractionated radiotherapy's feasibility and acute toxicity using the first Spanish 0.35T MR-LINAC in 37 patients. Prostate tumors (59.46%) were the most treated, followed by pancreatic tumors (32.44%). Treatment adaptation was successful, with manageable acute toxicity profiles. For prostate cancer, hypo-fractionated radiotherapy yielded promising outcomes with minimal toxicity, predominantly grade I and II cystitis. Pancreatic cancer patients received ablative dose radiotherapy with acceptable toxicity. Quality assurance measures demonstrated precise dose delivery. Overall, our study highlights the safety and feasibility of hypo-fractionated radiotherapy on a 0.35T MR-LINAC, particularly for challenging anatomical sites like prostate and pancreatic tumors, supporting its potential as an effective cancer treatment strategy. This observational, descriptive, longitudinal, and prospective basket-type study (Registry #5289) prospectively evaluated the feasibility and acute toxicity of hypo-fractionated radiotherapy on the first 0.35T MR-LINAC in Spain. A total of 37 patients were included between August and December 2023, primarily with prostate tumors (59.46%), followed by pancreatic tumors (32.44%). Treatment regimens typically involved extreme hypo-fractionated radiotherapy, with precise dose delivery verified through quality assurance measures. Acute toxicity assessment at treatment completion revealed manageable cystitis, with one case persisting at the three-month follow-up. Gastrointestinal toxicity was minimal. For pancreatic tumors, daily adaptation of organ-at-risk (OAR) and gross tumor volume (GTV) was practiced, with median doses to OAR within acceptable limits. Three patients experienced gastrointestinal toxicity, mainly nausea. Overall, the study demonstrates the feasibility and safety of extreme hypo-fractionated radiotherapy on a 0.35T MR-LINAC, especially for challenging anatomical sites like prostate and pancreatic tumors. These findings support the feasibility of MR-LINAC-based radiotherapy in delivering precise treatments with minimal toxicity, highlighting its potential for optimizing cancer treatment strategies. [ABSTRACT FROM AUTHOR]

Simple Summary: Advanced triple-negative breast cancer (TNBC) remains an extremely challenging situation in oncology, where new therapeutical strategies are desperately needed. Immunotherapy has opened a window of opportunity in this setting, with some promising results with chemo-immunotherapeutic schedules based on anti-PD1/PD-L1 agents, especially in the PD-L1-positive cohort. However, there is certainly room for improvement; thus, new schemes that could potentially boost synergism against cancer cells must be explored. This work analyzes the effects of combination therapy with anti-PD1 (pembrolizumab) and gemcitabine, specifically in the TNBC cohort of the PANGEA-Breast trial. Patients included in this study were not selected by PD-L1 status, and most of them were also heavily pretreated, which could explain the modest objective response rate of 15% achieved. Complementary translational subanalyses, focused on T infiltrating lymphocytes, myeloid-derived suppressor cells, and PD-L1 were accomplished. The PANGEA-Breast trial evaluated a new chemo-immunotherapeutic combination that would synergistically induce long-term clinical benefit in HER2-negative advanced breast cancer patients. Treatment consisted of 21-day cycles of 200 mg of pembrolizumab (day 1) plus gemcitabine (days 1 and 8). The primary objective was the objective response rate (ORR). The tumor infiltrating lymphocytes (TILs) density and PD-L1 expression in tumor, and the myeloid-derived suppressor cells (MDSCs) level in peripheral blood, were analyzed to explore associations with treatment efficacy. Considering a two-stage Simon's design, the study recruitment was stopped after its first stage as statistical assumptions were not met. A subset of 21 triple-negative breast cancer (TNBC) patients was enrolled. Their median age was 49 years; 15 patients had visceral involvement, and 16 had ≤3 metastatic locations. Treatment discontinuation due to progressive disease (PD) was reported in 16 patients. ORR was 15% (95% CI 3.2–37.9). Four patients were on treatment >6 months before PD. Grade ≥3 treatment-related adverse events were observed in 8 patients, where neutropenia was the most common. No association was found between TILs density, PD-L1 expression or MDSCs levels and treatment efficacy. ORR in TNBC patients also did not meet the assumptions, but 20% were on treatment >6 months. [ABSTRACT FROM AUTHOR]