Treatment delays during radiotherapy for head and neck cancer (HNC) are a well-established factor negatively affecting clinical outcomes, with similar trends observed in other cancers. In this first part of a two-part review, we assessed the impact of overall treatment time (OTT) prolongation on locoregional control (LRC) and survival (SV) in cervical cancer (CC), prostate cancer (PC), and anal cancer (AC), while updating evidence for HNC. A comprehensive literature search was performed in evidence-based databases, including MEDLINE, identifying studies evaluating the relationship between OTT prolongation and outcomes. Particular attention was paid to the strength of evidence, distinguishing univariate analysis from multivariate analysis (MV-An). For CC, 37 articles were identified, with 88.8% reporting a detrimental impact on LRC and/or SV, mostly supported by MV-An. In AC, 15 studies were found, with 33.3% showing negative impacts, although with weaker evidence. For PC, 12 articles were reviewed, with 66.6% demonstrating detrimental effects mainly on LRC or biochemical control, and occasional associations with cancer-specific SV. Recent studies in HNC reinforced prior findings. When available, radiobiological parameters and practical recommendations are provided. In conclusion, strong evidence confirms that prolonged OTT worsens outcomes in HNC and CC, with less consistent but relevant effects in PC and AC.

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.

Background/Objectives: In Spain, pancreatic ductal adenocarcinoma (PDAC) is the seventh leading cause of cancer-related death, with only 20% of patients eligible for surgery at diagnosis. For the remaining majority, prognosis is poor and effective non-surgical strategies are needed. Stereotactic MR-guided adaptive radiotherapy (SMART) may facilitate the delivery of ablative doses of radiation safely with low toxicity. This study reports the first national experience in Spain with SMART for patients with borderline resectable (BRPC) or locally advanced pancreatic cancer and evaluates its feasibility, safety, and early clinical outcomes. Methods: A prospective observational study was conducted including 28 patients with histologically confirmed BRPC or LAPC treated between August 2023 and December 2024. All patients received induction chemotherapy—mainly FOLFIRINOX (57.1%)—followed by SMART delivered in five fractions (40–50 Gy) using a 0.35T MR-guided linear accelerator. Daily online adaptive recontouring and replanning were performed for all 140 treatment fractions. Toxicities were assessed using CTCAE v5.0, and survival outcomes were estimated using Kaplan–Meier analysis. Results: The median patient age was 67 years, and 71.4% of tumors were located in the pancreatic head. At a median follow-up of 7.4 months after SMART (12.25 months from diagnosis), 6-month local progression-free survival (LPFS) was 89.3% from the start of SMART and 82.1% from diagnosis. Distant progression-free survival (DPFS) at 6 and 12 months was 92.9% and 68.2%, respectively. Median progression-free survival (PFS) was 11.5 months, and the median treatment-free interval was 5.7 months. Median overall survival (OS) was not reached; 6- and 12-month OS rates were 89.3% and 74.1%, respectively. Treatment-related toxicity was limited to grade 2 abdominal pain in 14.3% of patients, with no grade ≥3 adverse events attributed to SMART. Conclusions: SMART is a feasible and safe treatment modality for BRPC and LAPC in real-world clinical practice. These encouraging early outcomes support further clinical investigation and broader implementation.

Objective: We aimed to provide real-world insights into the management of non-small cell lung cancer stage III (NSCLC-SIII) in Spain. Methods: The GOECP-SEOR group conducted an observational, retrospective, multicenter study in which data from patients diagnosed with NSCLC-SIII treated in Spanish radiotherapy departments (RTDs) were collected. Results: A total of 1505 NSCLC-SIII patients from 35 RTDs from 2018 to 2021 were recruited. A total of 871 patients (57.9%) received concurrent chemoradiotherapy (cCRT), and 390 patients (25.91%) received maintenance durvalumab. The immunotherapy (IT) was well tolerated, with Common Terminology Criteria for Adverse Events (CTCAE) Grade 0–2 toxicity observed in 85% of the patients (295 patients). The median overall survival (OS) was 26 months (95% CI 9.4-Not Reached NR). There was a statistically significant difference when patients were stratified by IT, with a median OS of 40 months (95% CI 22.1-NR) in the IT maintenance cohort compared with 19.4 months (95% CI 7.1–58.1) in the non-IT cohort. Differences were also noted in progression-free survival (PFS), with a median PFS of 20.8 months (95% CI 9.6-NR) in the IT cohort versus 8.4 months (95% CI 3.1–25.1) in the non-IT cohort. These differences remained significant according to the multivariate model (OS: HR 0.45 [95% CI 0.36–0.56], p < 0.001; PFS: HR 0.5 [95% CI 0.42–0.59], p < 0.001). Conclusions: The management of NSCLC-SIII patients can vary, leading to differences in treatment outcomes. The treatment of lung cancer in NSCLC-SIII patients in RTDs across Spain aligns with international guidelines and expert recommendations.